• Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the bladder. Variant pathology are allowed
• Tumor with specified fibroblast growth factor receptor (FGFR) mutations or fusions
• Bacillus Calmette- Guerin (BCG)-unresponsive after adequate BCG therapy or BCG experienced participants
• Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only)
• Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-1
• Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
• A woman of childbearing potential must have a negative pregnancy test (beta-hCG [beta-human chorionic gonadotropin]) (urine or serum) within 7 days before randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3)
• Adequate bone marrow, liver, and renal function as specified in the protocol
• Histologically confirmed, muscle-invasive (T2 or higher stage) urothelial carcinoma of the bladder
• Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous CIS of the bladder
• Prior treatment with an FGFR inhibitor
• Active malignancies other than the disease being treated under study. The only allowed exceptions are: (a) skin cancer treated within the last 24 months that is considered completely cured (b) adequately treated lobular carcinoma in situ (LCIS) and ductal CIS (c) history of localized breast cancer and receiving antihormonal agents, or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy
• Current central serous retinopathy or retinal pigment epithelial detachment of any grade

Subjects must fulfill all of the following inclusion criteria: 1. Previous participation in an Astex-sponsored ASTX727 clinical trial (including, but not limited to studies ASTX727-01, ASTX727-02, and ASTX727-04) in which the subject was treated with ASTX727 and was still on active treatment with ASTX727 at the time of study completion as determined by Astex. 2. Subject is considered to be benefitting from ASTX727 treatment in the opinion of the treating investigator at the time of parent study completion (Subjects must not be withdrawn from the parent study until eligibility for this study is confirmed). 3. Subject is able to understand and comply with the study procedures and understands the risks involved in the study. 4. Subject provides written informed consent before undergoing any study-specific procedure. 5. Women of childbearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential must agree to practice 2 highly effective contraceptive methods of birth control and must agree not to become pregnant for 6 months after completing treatment; men with female partners of childbearing potential must agree to practice 2 highly effective contraceptive measures and must agree not to father a child while receiving ASTX727 and for at least 3 months after completing ASTX727 treatment. Exclusion Criterion: 1. Any subject who, in the opinion of the investigator, may have other conditions, organ dysfunction, or for whom safety data from parent study participation suggests the risks of continuing treatment with ASTX727 may outweigh the benefits.

• Diagnosis of: 1. CLL with an indication for treatment based on the Investigator's opinion and measurable disease, or 2. SLL (lymphadenopathy and/or splenomegaly and < 5×10^9 CD19+ CD5+ clonal B lymphocytes/L [< 5000/µL] in the peripheral blood at diagnosis with measurable disease that is biopsy-proven SLL)
• Subjects (other than those in the ibrutinib + JCAR017 combination therapy cohort) must have received and failed Bruton tyrosine kinase inhibitor (BTKi) treatment or have been deemed ineligible for BTKi therapy.
• Subjects (other than those in the ibrutinib + JCAR017 combination therapy cohort) must have received previous treatment as follows: 1. Subjects with CLL or SLL and high-risk features must have failed at least 2 lines of prior therapy. 2. Subjects with CLL or SLL and standard-risk features must have failed at least 3 lines of prior therapy.
• Subjects in the ibrutinib + JCAR017 combination therapy cohort must either: 1. be receiving ibrutinib and progressing at the time of study enrollment 2. be receiving ibrutinib for at least 6 months with a response less than complete response/remission (CR) and have high-risk features as defined in inclusion criterion 5a 3. have BTK or PLCgamma2 mutations per local laboratory assessment, with or without progression on ibrutinib 4. have previously received ibrutinib and have no contraindications to restarting ibrutinib
• Eastern Cooperative Oncology Group performance status of ≤ 1
• Assessed by the Investigator to have adequate bone marrow function to receive lymphodepleting chemotherapy
• Adequate organ function, defined as: 1. Serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN) OR calculated creatinine clearance > 30 mL/min 2. Alanine aminotransferase ≤ 5 × ULN and total bilirubin < 2.0 mg/dL (or < 3.0 mg/dL for subjects with Gilbert's syndrome or leukemic infiltration of the liver) 3. Adequate pulmonary function, defined as ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 dyspnea and saturated oxygen (SaO2) ≥ 92% on room air 4. Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% as assessed by echocardiogram or multiple uptake gated acquisition scan performed within 30 days prior to determination of eligibility
• Subject either currently has central vascular access or is a candidate to receive central vascular access or peripheral vascular access for leukapheresis procedure.
• If prior CD19-targeted therapy has been administered, subject must have CD19-positive disease confirmed by immunohistochemistry or flow cytometry since completing the prior CD19-targeted therapy.
• Subjects in ibrutinib + JCAR017 combination cohort must have progressed on a BTKi and have received prior therapy with venetoclax
• Subjects in venetoclax + JCAR017 combination cohort must: 1. have failed at least 1 prior line of therapy, including failed BTKi therapy or have been deemed ineligible to receive BTKi 2. be venetoclax naive (required for dose expansion) or 3. if prior venetoclax (only for dose escalation) 4. have no contraindictions to re-initiation of venetoclax based on prior intolerance and have had at least 6 months elapsed since the last dose of venetoclax, if either, best response was stable disease, or subject experienced disease progression on venetoclax, or within 6 months of venetoclax discontinuation
• subjects in the venetoclax + JCAR017 combination must have hemoglobin >=9 g/dL, absolute neutrophil count >=500mm3 and platelets>= 75,000/mm3, unless cytopenias are judged by investigator to be due to CLL infiltration of the bone marrow
• must have diagnosis of CLL or SLL with an indication for treatment based on the investigator's opinion and measurable disease (any of the following measurable lymph nodes ≥1.5 cm in the greatest transverse diameter and/or hepatomegaly or splenomegaly) and demonstration of CLL cells in the peripheral blood by flow cytometry
• Subjects with known active central nervous system (CNS) involvement by malignancy. Those with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment with no evidence of symptomatic disease and stable abnormalities on repeat imaging.
• History of another primary malignancy that has not been in remission for at least 2 years. (The following are exempt from the 2-year limit: nonmelanoma skin cancer, completely resected stage 1 solid tumor with low risk for recurrence, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has been completely resected.)
• Subjects with Richter's transformation
• Prior treatment with any gene therapy product
• Active hepatitis B, active hepatitis C, or active human immunodeficiency virus (HIV) infection
• Systemic fungal, bacterial, viral, or other infection that is not controlled
• Presence of acute or extensive chronic graft versus host disease (GVHD)
• History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
• History or presence of clinically relevant CNS pathology such as epilepsy, generalized seizure disorder, aphasia, stroke with current neurologic sequelae, severe brain injuries, dementia, Parkinson's disease, cerebellar disease,cerebral edema, or psychosis
• Pregnant or nursing (lactating) women
• Use of any of the following medications or treatments within the noted time prior to leukapheresis: 1. Alemtuzumab within 6 months prior to leukapheresis 2. Allogeneic hematopoietic stem cell transplant within 100 days prior to leukapheresis 3. Cladribine within 3 months prior to leukapheresis 4. Donor lymphocyte infusions (DLI) within 2 months prior to leukapheresis 5. Radiation including large bone marrow fields such as sternum or pelvis within 6 weeks prior to leukapheresis 6. Fludarabine within 4 weeks prior to leukapheresis 7. GVHD therapies such as calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate mofetil, rapamycin, or immunosuppressive antibodies (such as anti-tumor necrosis factor-α [TNFα], anti-interleukin-6 [IL-6], or anti-interleukin-6 receptor [IL 6R]) within 4 weeks prior to leukapheresis 8. Cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or melphalan within 2 weeks prior to leukapheresis 9. Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis 10. Anti-CD20 monoclonal antibodies within 7 days prior to leukapheresis 11. Venetoclax within 4 days prior to leukapheresis 12. Idelalisib or duvelisib within 2 days prior to leukapheresis 13. Lenalidomide within 1 day prior to leukapheresis 14. Experimental agents, including off-label use of approved drugs (with the exception of acalabrutinib which may be continued up to the day before leukapheresis), within 4 weeks prior to leukapheresis unless progression is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis
• Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the Investigator; or subject unwillingness or inability to follow the procedures required in the protocol
• Progressive vascular tumor invasion, thrombosis, or embolism
• Deep vein thrombosis or embolism not managed on a stable regimen of anticoagulation
• Use of any of the following medications or treatments within the noted time prior to leukapheresis lenalidomide or acalabrutinib within 1 day prior to leukapheresis experimental agents, including off-label use of approved drugs, within 4 weeks prior to leukapheresis.
• Venous thrombosis or embolism requiring treatment but not managed on a stable regimen of anticoagulation
• For subjects in the venetoclax + JCAR017 combination cohorts only, concomitant treatment with CYP3A moderate/strong inducers or moderate/strong inhibitors which cannot be discontinued

• Has a confirmed diagnosis of endogenous Cushing syndrome
• Meets at least one of the following criteria:
• Has Type 2 diabetes mellitus
• Has impaired glucose tolerance
• Has hypertension
• Has non-endogenous source of hypercortisolemia
• Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
• Has poorly controlled hypertension
• Has poorly controlled diabetes mellitus
• Has severe renal insufficiency

• Male or female subject aged ≥40 years on the day of signing the Informed Consent Form (ICF).
• A diagnosis of IPF within 5 years prior to the screening visit, as per applicable American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines at the time of diagnosis.
• Chest high-resolution computed tomography (HRCT) historically performed within 12 months prior to the screening visit and according to the minimum requirements for IPF diagnosis by central review based on subject's HRCT only (if no lung biopsy (LB) available), or based on both HRCT and LB (with application of the different criteria in either situation). If an evaluable HRCT <12 months prior to screening is not available, an HRCT can be performed at screening to determine eligibility, according to the same requirements as the historical HRCT.
• Subjects receiving local standard of care for the treatment of IPF, defined as either pirfenidone or nintedanib, at a stable dose for at least two months before screening, and during screening; or neither pirfenidone or nintedanib (for any reason). A stable dose is defined as the highest dose tolerated by the subject during those two months.
• The extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan (investigator-determined).
• Meeting all of the following criteria during the screening period: FVC ≥45% predicted of normal, Forced expiratory volume in 1 second (FEV1)/FVC ≥0.7, diffusing capacity of the lung for carbon monoxide (DLCO) corrected for Hb ≥30% predicted of normal.
• Estimated minimum life expectancy of at least 30 months for non IPF related disease in the opinion of the investigator.
• Male subjects and female subjects of childbearing potential agree to use highly effective contraception/preventive exposure measures from the time of first dose of investigational medicinal product (IMP) (for the male subject) or the signing of the ICF (for the female subject), during the study, and until 90 days (male) or 30 days (female) after the last dose of IMP.
• Able to walk at least 150 meters during the 6-Minute Walk Test (6MWT) at screening Visit 1; without having a contraindication to perform the 6MWT or without a condition putting the subject at risk of falling during the test (investigator's discretion). The use of a cane is allowed, the use of a stroller is not allowed at all for any condition. At Visit 2, for the oxygen titration test, resting oxygen saturation (SpO2) should be ≥88% with maximum 6 L O2/minute; during the walk, SpO2 should be ≥83% with 6 L O2/minute or ≥88% with 0, 2 or 4 L O2/minute.
• History of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, prostate cancer that has been medically managed through active surveillance or watchful waiting, squamous cell carcinoma of the skin if fully resected, and Ductal Carcinoma In Situ).
• Acute IPF exacerbation within 6 months prior to screening and/or during the screening period. The definition of an acute IPF exacerbation is as follows: Previous or concurrent diagnosis of IPF; Acute worsening or development of dyspnea typically < 1 month duration; Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern and deterioration not fully explained by cardiac failure or fluid overload.
• Lower respiratory tract infection requiring antibiotics within 4 weeks prior to screening and/or during the screening period.
• Interstitial lung disease associated with known primary diseases (e.g. sarcoidosis and amyloidosis), exposures (e.g. radiation, silica, asbestos, and coal dust), or drugs (e.g. amiodarone).
• Diagnosis of severe pulmonary hypertension (investigator determined).
• Unstable cardiovascular, pulmonary (other than IPF), or other disease within 6 months prior to screening or during the screening period (e.g. acute coronary disease, heart failure, and stroke).
• Had gastric perforation within 3 months prior to screening or during screening, and/or underwent major surgery within 3 months prior to screening, during screening or have major surgery planned during the study period.
• Moderate to severe hepatic impairment (Child-Pugh B or C) and/or abnormal liver function test (LFT) at screening, defined as aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT), and/or total bilirubin ≥1.5 x upper limit of the normal range (ULN), and/or gamma glutamyl transferase (GGT) ≥3 x ULN. Retesting is allowed once for abnormal LFT.
• Abnormal renal function defined as estimated creatinine clearance, calculated according to Cockcroft-Gault calculation (CCr) <30 mL/min. Retesting is allowed once.
• Use of any of the following therapies within 4 weeks prior to screening and during the screening period, or planned during the study: warfarin, imatinib, ambrisentan, azathioprine, cyclophosphamide, cyclosporine A, bosentan, methotrexate, sildenafil (except for occasional use), prednisone at steady dose >10 mg/day or equivalent.

1. Age 18 years and older 2. Admitted to Cardiovascular ICU (CVICU) after coronary artery bypass grafting (CABG), isolated valve repair/replacement, or CABG + valve repair/replacement 3. Cardiac surgery performed via median sternotomy 1. BMI>40 2. Refusal to be consented 3. Prior or current lung transplant patients

• Have signed the current approved informed consent form. Participants under 18 years of age (in the Netherlands and other applicable regions, participants under 16 years of age) will sign an approved informed assent form and must also have a signed parental/legal guardian consent.
• Have a genotype-confirmed mutation of chemokine (C-X-C motif) receptor 4 (CXCR4) consistent with WHIM phenotype.
• Agree to use a highly effective form of contraception.
• Be willing and able to comply with the protocol.
• Have confirmed ANC ≤400 cells/µL during screening, obtained while participant has no clinical evidence of infection. Inclusion Criteria for the Open-Label Period:
• Completed the Randomized Period; or
• Granted Early Release from the Randomized Period.
• Has known systemic hypersensitivity to the mavorixafor drug substance, its inactive ingredients, or the placebo.
• Is pregnant or breastfeeding.
• Has any medical or personal condition, which in the opinion of the Investigator may potentially compromise the safety or compliance of the participant or may preclude the participant's successful completion of the clinical study. Exclusion Criteria for the Open-Label Period:
• Participants who experience any treatment-limiting toxicity (TLT) will be excluded from participating in the Open-Label Period.

• Step 1 Patient Registration Eligibility Criteria
• Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
• 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
• Clinical stage T2-T4aN0/xM0 disease
• Medically appropriate candidate for radical cystectomy as assessed by surgeon
• No concomitant multifocal carcinoma in situ; a single focus is allowed
• A single muscle-invasive bladder tumor measuring ≤5 cm in size as defined by the surgeons at cystoscopic evaluation. When documented, pathologic size at cystoscopy and TURBT will take precedence over radiographic measurements of tumor size.
• No clinical or radiographic evidence for locally advanced or metastatic disease
• No prior anti-PD-1 or anti PD-L1 therapies, or systemic chemotherapy within the past 5 years (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x6 doses and maintenance therapy); BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed. Intravesical chemotherapy is allowed.
• No prior radiation therapy to the bladder or prostate
• No major surgery or radiation therapy =< 4 weeks of registration (TURBT is allowed).
• Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Platelet count >= 100,000/mm^3
• Calculated creatinine clearance ≥ 55 mL/min using formula per institutional standard or investigator's discretion. The same formula should be used to calculate all subsequent creatinine clearances.
• Total bilirubin =< 1.5 x upper limit of normal (ULN) * (For patients with documented Gilbert's syndrome Total Bilirubin =< 3 x ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
• Alkaline phosphatase =< 2.5 x ULN
• No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
• No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
• No pre-existing sensory grade >= 2 neuropathy
• No pre-existing grade >= 2 hearing loss
• No serious intercurrent medical or psychiatric illness, including serious active infection
• None of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
• No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
• No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
• No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
• Step 2 Patient Registration Eligibility Criteria
• Patients must have completed 4 or more cycles of protocol-directed chemotherapy and DDR gene results must be available
• Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene alteration)
• Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pre-treatment TURBT deoxyribonucleic acid (DNA)
• Cystoscopy and imaging performed to determine stage/treatment assignment

Inclusion criteria: Parts A, B, C, D and E:
• Patients must be postmenopausal women
• Histological diagnosis of breast adenocarcinoma
• Locally advanced or metastatic disease
• Either primary tumor or any metastatic site to be positive for Estrogen Receptors (ER+) and negative for HER2 (HER2-) receptor
• Patients previously treated with endocrine therapy for advanced disease: at least 6 months exposure to endocrine therapy (Patients with early progression on adjuvant endocrine therapy or who progressed on adjuvant endocrine therapy within 12 months after completion are eligible), and in part D, no more than 2 prior lines of endocrine therapy are allowed
• Patients previously treated with chemotherapy for advanced disease: no more than 3 prior chemotherapeutic regimens in Part A, and no more than 1 prior chemotherapeutic regimen in Parts B, C, D and E (including Antibody Drug Conjugates)
• Measurable lesion Exclusion criteria:
• Medical history or ongoing gastrointestinal disorders that could affect absorption of SAR439859 and/or palbociclib (including difficulties with swallowing capsules)
• Patient with any other cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or any other cancer from which the patient has been disease free for >3 years)
• Patients with known brain metastases
• Treatment with anticancer agents (including investigational drugs) less than 2 weeks before first study treatment starts (less than 4 weeks if the anticancer agents were antibodies)
• Prior treatment with another selective ER down-regulator (SERD) (except fulvestrant) with a washout of at least 6 weeks prior to the first study drug administration
• Inadequate hematological and biochemical lab tests
• Patients with Gilbert disease
• Treatment with human immunodeficiency virus (HIV)-antiviral, antifungal and antioxidant agents less than 2 weeks before study treatment starts
• Treatment with strong and moderate cytochrome P450 (CYP) 3A or CYP2C8 inducers within 2 weeks before first study treatment
• Treatment with strong CYP3A inhibitors within 2 weeks before first study treatment starts
• More than one prior cyclin-dependent kinase (CDK) 4/6 inhibitor based therapy.
• No prior CDK4/6 exposure is required for patients with early progression on adjuvant endocrine therapy or who progressed on adjuvant endocrine therapy within 12 months after completion of adjuvant endocrine therapy Part A only:
• Patients with liver metastases only Part D only:
• Prior therapy with any selective CDK4/6 inhibitor, phosphoinositide 3-kinase (PI3K) inhibitors and mammalian target of rapamycin (mTOR) inhibitors Part E only:
• Any treatment with weak CYP3A inducer and all CYP3A inhibitors within 2 weeks before midazolam administration
• Any contraindications to midazolam (in accordance with the applicable label)
• Use of any herbal medicines 1 week, and grapefruit juice for 72 hours before midazolam administration and up to the end of PK sampling following the last midazolam administration
• Patients older than 60 years The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Inclusion criteria will be the same for Phase I and Phase II. 1. Pathologically proven diagnosis of stage I-IVB squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx status post gross total resection with pathology showing one or more of the following intermediate risk factors: T3/4 disease, positive lymph node(s), close margin(s), perineural invasion, and/or lymphovascular invasion 2. Age ≥18 years 3. ECOG performance status 0-2 4. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Medically acceptable birth control (contraceptives) includes:
• approved hormonal contraceptives (such as birth control pills, patch or ring; Depo-Provera, Implanon), or
• barrier methods (such as condom or diaphragm) used with a spermicide 5. Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential. 6. Ability to understand and the willingness to sign a written informed consent Phase I: 1. Distant metastasis 2. Stage I and II glottic squamous cell carcinoma 3. High risk factors following surgical resection requiring concurrent chemotherapy: positive margin(s) and/or extranodal extension 4. Feeding tube dependence at baseline assessment. 5. Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer. For thyroid cancer, surgery may occur before or after treatment, provided all other eligibility criteria are met. For prostate cancer, patient should not be receiving active treatment. 6. Prior invasive malignancy with an expected disease-free interval of less than 3 years 7. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields 8. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study. 9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements 10. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. 11. History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant Phase II: The exclusion criteria will be the same as Phase I except for feeding tube dependence. Patients who are feeding tube dependent are excluded from Phase I to accurately assess treatment associated toxicity affecting swallowing and oral intake. During Phase II, patients who are feeding tube dependent will be eligible to enroll and stratified at randomization.

Inclusion Criteria 1. Have histologically or cytologically confirmed, invasive urothelial carcinoma with susceptible FGFR3 alterations within 120 days following nephroureterectomy, distal ureterectomy, or cystectomy 2. If the patient received neoadjuvant chemotherapy, pathologic stage at surgical resection must be AJCC Stage ≥ ypT2 and/or yN+. 3. If the patient did not receive neoadjuvant chemotherapy: 1. Must be ineligible to receive cisplatin-based adjuvant chemotherapy per the Galsky criteria:
• creatinine clearance < 60cc/min or
• ≥ Grade 2 hearing loss or
• ≥ Grade 2 neuropathy) 2. Pathologic stage must be AJCC Stage ≥pT2 pN0-2 M0 (post-lymphadenectomy or no lymphadenectomy [pNx]) for upper tract disease. 3. Pathologic stage should be AJCC Stage ≥pT3 or pN+ (bladder cancer). 4. Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. 5. Patients must have no evidence of metastatic disease based on screening CT or MRI. 1. Presence of positive surgical margins following nephroureterectomy, distal ureterectomy, or cystectomy. 2. Have received Bacillus Calmette-Guerin (BCG) or other intravesical therapy for Non-Muscle Invasive Bladder Cancer (NMIBC) within the previous 30 days. 3. Have previously or currently is receiving treatment with a mitogen-activated protein kinase (MEK) or selective FGFR inhibitor. 4. Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (eg, active ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) 5. Have current evidence of corneal or retinal disorder/keratopathy. 6. Have a history and/or current evidence of extensive tissue calcification. 7. Have current evidence of endocrine alterations of calcium/phosphate homeostasis (eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis), unless well controlled. 8. Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. 9. Clinically significant cardiac disease. 10. Recent (< 3 months prior to first dose of study drug) transient ischemic attack or stroke.

• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate. Patients with pure small cell carcinoma* (SCC), sarcomatoid, or squamous cell carcinoma are not eligible. (*morphology must be consistent with SCC; synaptophysin or chromogranin positive by immunohistochemical staining is insufficient to diagnose SCC).
• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have an intact prostate. No prior local therapy for prostate adenocarcinoma is allowed (e.g., brachytherapy, high-intensity focused ultrasound [HIFU], cryotherapy, laser ablative therapies). Any prior therapy for benign conditions, such as obstruction, are acceptable (e.g., transurethral resection of the prostate, greenlight laser ablation, microwave ablation).
• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have evidence of metastatic disease on technetium bone scan and computed tomography (CT) or magnetic resonance imaging (MRI) within 42 days prior to starting standard systemic therapy. Metastatic disease that is detected by positron emission tomography (PET) scan only (sodium fluoride [NaF], prostate-specific membrane antigen [PSMA], anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid [FACBC], carbon [C]11) but not conventional imaging (technetium [Tc]99 bone scan, CT or MRI) or solitary metastases by conventional imaging, must be confirmed histologically or cytologically.
• STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients with known brain metastases are not eligible. Brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms suggestive of brain metastasis. If brain imaging studies are performed, they must be negative for disease.
• STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received no more than 28 weeks of standard systemic therapy (SST). SST is defined as current National Comprehensive Cancer Network (NCCN) guidelines for metastatic prostate cancer.
• STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have progressed while on SST.
• STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients with oligometastatic prostate cancer may receive metastasis directed therapy to up to four sites of disease prior to randomization.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a complete physical examination and medical history within 28 days prior to registration.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA documented prior to initiation of SST and within 28 days prior to registration. Any additional PSAs measured while receiving SST should be recorded.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone lab documented within 28 days prior to randomization. Any additional testosterone labs measured while receiving SST should be recorded as well as pretreatment initiation if available.
• STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated stage 0, I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
• STEP 1 REGISTRATION: SPECIMEN SUBMISSION CRITERIA: Patients must be offered the opportunity to participate in translational medicine studies and specimen banking for future studies.
• STEP 1 REGISTRATION: QUALITY OF LIFE CRITERIA: Patients who can complete Patient-Reported Outcome instruments in English, Spanish or French, must participate in the quality of life studies.
• STEP 1 REGISTRATION: REGULATORY CRITERIA: Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
• STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
• STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have no evidence of disease progression during the 28 weeks of SST by PSA measure, bone scan and CT or MRI or symptomatic deterioration (as defined by physician discretion) within 28 days prior to randomization.
• STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have consultation with a urologist and have surgically resectable disease regardless of definitive treatment intent or randomization.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received between 22 and 28 weeks of SST as measured from the date of first hormonal therapy or surgical castration. SST is defined by current NCCN guidelines for metastatic prostate cancer.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not be planning to receive docetaxel after randomization.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Any toxicities from SST must have resolved to =< grade 1 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) prior to randomization.
• STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients may have received elective metastasis directed therapy to oligometastatic sites (=< 4 sites). All treatment must be completed prior to randomization.
• STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA performed within 28 days prior to randomization.
• STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone < 50 ng/dL within 28 days prior to randomization.
• STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a Zubrod performance status of 0 ? 1 within 28 days prior to randomization.

• Has a histologically- or cytologically-confirmed advanced (metastatic and/or unresectable) solid tumor (except breast or ovarian cancers whose tumor has a germline or somatic BRCA mutation) that is not eligible for curative treatment and for which standard of care therapy has failed. Participants must have progressed on or be intolerant to standard of care therapies that are known to provide clinical benefit. There is no limit on the number of prior treatment regimens.
• Has either centrally-confirmed known or suspected deleterious mutations in at least 1 of the genes involved in HRR or centrally-confirmed HRD.
• For participants receiving prior platinum (cisplatin, carboplatin, or oxaliplatin either as monotherapy or in combination) for advanced (metastatic and/or unresectable) solid tumor, have no evidence of disease progression during the platinum chemotherapy.
• Has measurable disease per RECIST 1.1 or PCWG-modified RECIST 1.1 as assessed by the local site Investigator/radiology and confirmed by BICR.
• Is able to provide a newly obtained core or excisional biopsy of a tumor lesion or either an archival formalin-fixed paraffin embedded (FFPE) tumor tissue block or slides.
• Has a life expectancy of at least 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 3 days of treatment initiation.
• Male participants must agree to use contraception during the treatment period and for at least 90 days (3 months) after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants must not be pregnant or breastfeeding. Additionally, female participants must either not be a woman of childbearing potential (WOCBP) or, if a WOCBP, agree to use contraception during the treatment period and for at least 30 days (1 month) after the last dose of study treatment.
• Has adequate organ function.
• Has a known additional malignancy that is progressing or has required active treatment in the last 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal carcinoma in situ, or cervical carcinoma in situ that has undergone potentially curative therapy are not excluded.
• Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
• Has known central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Participants with previously treated brain metastases may participate if radiologically stable, clinically stable, and without requirement for steroid treatment for at least 14 days prior to the first dose of study treatment.
• Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 28 days prior to the first dose of study treatment.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has known active hepatitis infection (i.e., Hepatitis B or C).
• Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
• Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (poly[ADP ribose]) polymerization (PARP) inhibitor.
• Has a known hypersensitivity to the components or excipients in olaparib.
• Has received previous allogenic bone-marrow transplant or double umbilical cord transplantation (dUCBT).
• Has received a whole blood transfusion in the last 120 days prior to entry to the study. Packed red blood cells and platelet transfusions are acceptable if not performed within 28 days of the first dose of study treatment.

• Histologically documented, unresectable locally advanced or metastatic urothelial carcinoma
• Measurable disease by investigator assessment according to RECIST v1.1
• Participants with prior definitive radiation therapy must have measurable disease per RECIST v1.1 that is outside the radiation field or has demonstrated unequivocal progression since completion of radiation therapy
• Participants must not have received prior systemic therapy for locally advanced or metastatic urothelial carcinoma with the following exceptions:
• Participants that received neoadjuvant chemotherapy with recurrence >12 months from completion of therapy are permitted
• Participants that received adjuvant chemotherapy following cystectomy with recurrence >12 months from completion of therapy are permitted
• Must be considered eligible to receive cisplatin- or carboplatin-containing chemotherapy, in the investigator's judgment
• Archival tumor tissue comprising muscle-invasive urothelial carcinoma or a biopsy of metastatic urothelial carcinoma must be provided for PD-L1 testing prior to randomization
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
• Adequate hematologic and organ function Exclusion Criteria
• Previously received enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADCs)
• Received prior treatment with a programmed cell death ligand-1 (PD-(L)-1) inhibitor for any malignancy, including earlier stage urothelial cancer (UC), defined as a PD-1 inhibitor or PD-L1 inhibitor
• Received prior treatment with an agent directed to another stimulatory or co inhibitory T-cell receptor
• Received anti-cancer treatment with chemotherapy, biologics, or investigational agents not otherwise prohibited by exclusion criterion 1-3 that is not completed 4 weeks prior to first dose of study treatment
• Uncontrolled diabetes
• Estimated life expectancy of less than 12 weeks
• Active central nervous system (CNS) metastases
• Ongoing clinically significant toxicity associated with prior treatment that has not resolved to ≤ Grade 1 or returned to baseline
• Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted.
• Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection.
• History of another invasive malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy
• Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class IV within 6 months prior to randomization
• Receipt of radiotherapy within 2 weeks prior to randomization
• Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 4 weeks prior to randomization
• Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin
• Active keratitis or corneal ulcerations
• History of autoimmune disease that has required systemic treatment in the past 2 years
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Prior allogeneic stem cell or solid organ transplant
• Received a live attenuated vaccine within 30 days prior to randomization

• Age greater than or equal to 1 month and less than or equal to 12 months at the time of randomization; AND
• Positive congenital CMV by urine culture or polymerase chain reaction test(PCR), OR saliva culture or PCR followed by confirmatory urine PCR by 21 days of age, OR urine culture or PCR after 21 days of age followed by newborn dry blood spot PCR; AND
• Confirmed sensorineural hearing loss (SNHL) by auditory brainstem response (ABR) testing. For ABR assessments, hearing loss is defined as levels greater than 25 dB normal hearing levels (NHL) at 1, 2, or 4 kHz in one or both ears.
• Imminent demise; OR
• Known hypersensitivity reaction to valganciclovir, ganciclovir, or any components of the investigational product formulation; OR
• ALT (Alanine Aminotransferase) five times baseline U/L, hepatomegaly, or significant gastrointestinal disorders (e.g., eosinophilic esophagitis, ulcerative colitis); OR
• Absolute neutrophil count (ANC) less than 500 cells/mm^3, Hemoglobin less than 8 g/dL, or platelets less than 50,000/mm^3, splenomegaly, or significant hematologic disorders (e.g., hemophilia, leukemia, sickle cell anemia); OR
• Creatinine clearance less than 60 mL/min/1.73m^2 or significant renal disorders (e.g., nephrotic syndrome); OR
• Receiving other antiviral medications or immune globulin therapy; OR
• Receiving other investigational drugs; OR
• Breast feeding from a mother receiving antiviral or immunosuppressive medication; OR
• Known HIV positive mother (risk of immunosuppression); OR
• Subject is currently using list of prohibited medication specified by the package insert; OR
• Other known cause contributing to SNHL (e.g., meningitis, aminoglycoside ototoxicity); OR
• Bilateral profound SNHL or auditory neuropathy spectrum disorder; OR
• Existing conductive hearing loss or mixed permanent hearing loss is present; OR
• Evidence of intracranial calcification; OR
• Evidence of hydrocephalus; OR
• Microcephaly; OR
• Presence of petechiae; OR
• Intrauterine growth retardation; OR
• Chorioretinitis, optic atrophy or pale optic nerves; OR
• Parent or guardian unable to speak English or Spanish; OR
• Subject exposed to a language other than English or Spanish a majority of the time; OR
• Subject unable to complete hearing assessments or parent/guardian unable to complete communication questionnaires; OR
• < 32 weeks gestational age at birth; OR
• Weight at the time of birth < 1800 g.

• Community-dwelling adults
• Age ≥75 years
• English or Spanish as primary language
• Clinically evident cardiovascular disease defined as prior myocardial Infarction (MI), prior stroke, prior revascularization procedure, or a secondary prevention indication for a statin (clinician determined)
• Hospitalization for a primary diagnosis of heart failure in the prior 12 months (Note: History of heart failure in the absence of recent hospitalization or clinically evident cardiovascular disease is not an exclusion)
• Dementia (clinically evident or previously diagnosed)
• Dependence in any Katz Basic Activities of Daily Living [ADL] (with the exception of urinary or bowel continence)
• Severe hearing impairment (preventing phone follow up)
• Unable to talk (preventing phone follow up)
• Severe visual impairment (preventing cognitive testing)
• Statin use in the past year or for longer than 5 years previously (participant reported)
• Ineligible to take atorvastatin 40 mg (clinician determined)
• Documented intolerance to statins
• Active Liver Disease
• Long-term use of daily colchicine, verapamil at any dose, or diltiazem at a dose >240mg/day.

• Each patient must meet the following criteria to be enrolled in this study. 1. Be able to and provide written informed consent and be willing and able to comply with all study procedures 2. Adult, 18 years and older 3. AL amyloidosis Mayo stage IIIa based on the 2013 European Modification of the 2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement at the time of Screening 4. Measurable hematologic disease at Screening as defined by at least one of the following: 1. Involved/Uninvolved Free Light Chain Difference (dFLC) > 4 mg/dL or 2. Involved Free Light Chain (iFLC) > 4 mg/dL with abnormal ratio or 3. Serum Protein Electrophoresis (SPEP) m-spike > 0.5 g/dL 5. Histopathological diagnosis of amyloidosis AND confirmation of AL derived amyloid deposits by at least one of the following: 1. Immunohistochemistry or 2. Mass spectrometry or 3. Characteristic electron microscopy appearance 6. Cardiac involvement as defined by: 1. Documented clinical signs and symptoms supportive of a diagnosis of heart failure in the setting of a confirmed diagnosis of AL amyloidosis in the absence of an alternative explanation for heart failure AND 2. At least one of the following: i. Endomyocardial biopsy demonstrating AL cardiac amyloidosis or ii. Echocardiogram demonstrating a mean left ventricular wall thickness (calculated as [IVSd+LPWd]/2) of > 12 mm at diastole in the absence of other causes (e.g., severe hypertension, aortic stenosis), which would adequately explain the degree of wall thickening or iii. Cardiac MRI with gadolinium contrast agent diagnostic or cardiac amyloidosis 7. Planned first-line treatment for plasma cell dyscrasia is a CyBorD-based regimen administered as Standard of Care (SoC) 8. Adequate bone marrow reserve and hepatic function as demonstrated by: 1. Absolute neutrophil count ≥ 1.0 x 109/L 2. Platelet count ≥ 75 x 109/L 3. Hemoglobin ≥ 9 g/dL 4. Total direct bilirubin ≤ 2 times the upper limit of normal (x ULN) unless due to Gilbert's syndrome. 5. Aspartate aminotransferase (AST) ≤ 3 x ULN 6. Alanine aminotransferase (ALT) ≤ 3 x ULN 7. Alkaline phosphatase (ALP) ≤ 5 x ULN (except for patients with hepatomegaly and isozymes specific to liver, rather than bone) 9. Women of childbearing potential (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective physician approved contraception from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of her PCD therapy, whichever is longer 10. Men must be surgically sterile or must agree to use effective physician approved contraception and refrain from donating sperm from Screening to at least 5 months following the last study drug administration or 12 months following the last dose of his PCD therapy, whichever is longer
• Patients who meet any of the following criteria will not be permitted entry to the study. 1. Have any other form of amyloidosis other than AL amyloidosis 2. Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure of 160 mg dexamethasone (or equivalent corticosteroid) since diagnosis of AL amyloidosis and prior to randomization is allowed. 3. Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma or POEMS syndrome 4. Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of > 30 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion 5. Taking prednisone or its equivalent > 10 mg/day 6. Taking doxycycline 7. Receiving dialysis 8. Planned stem cell transplant during the first 6 months of protocol therapy. Stem cell collection during the protocol therapy is permitted. 9. Have had myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias within 6 months prior to screening or percutaneous cardiac intervention with recent stent or coronary artery bypass grafting within 4 months prior to screening. Exacerbation of chronic condition or new acute condition will require discussion and approval by the Medical Monitor. 10. Left Ventricular Ejection Fraction (LVEF) is < 40% by echocardiogram at Screening 11. Have severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area < 1.0 cm2) or severe congenital heart disease 12. Have history of sustained ventricular tachycardia or aborted ventricular fibrillation or a history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is indicated but not placed. (Participants who do have a pacemaker or ICD are allowed in the study.) 13. QT corrected by Fridericia (QTcF) is > 550 msec. Participants who have a pacemaker may be included regardless of calculated QTc interval. 14. There is evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following: 1. First degree Atrioventricular (AV)-block 2. Second degree AV-block Type 1 (Mobitz Type 1/Wenckebach type) 3. Right or left bundle branch block 4. Atrial fibrillation with a controlled ventricular rate. (An uncontrolled ventricular rate [i.e., > 110 beats per minute] determined by an average of three beats in lead II or representative beats in lead II is not allowed) 15. Have had major surgery within 4 weeks of randomization or is planning major surgery during the study. Patients with surgical procedures conducted under local anesthesia may participate 16. There is active malignancy (including lymphoma) with the exception of any of the following: 1. Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer 2. Adequately treated stage I cancer from which the patient is currently in remission and has been in remission for > 2 years 3. Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen < 10 mg/mL 4. Other localized and/or low risk malignancies may be permitted with Medical Monitor approval. 17. Have received an investigational drug/device in another clinical investigational study within 60 days before Screening 18. Hypersensitivity to the study drug 19. Have received a live vaccine within 4 weeks prior to first dose of CyBorD 20. Women who are breast feeding 21. Have any other medical, social or psychological factors that could affect the patient's safety or ability to consent personally or comply with study procedures.

1. Have histologically confirmed advanced or metastatic castration-resistant prostate cancer, bladder cancer, melanoma, non-small cell lung cancer, pancreatic cancer, colorectal cancer, gastric cancer, esophageal cancer, ovarian cancer, and head neck squamous cell carcinoma. Or, Have histologically confirmed metastatic pancreatic adenocarcinoma. Recurrent unresectable pancreatic cancer is acceptable as long as the treatment is first-line. 2. Have not received any approved chemotherapy, except in the adjuvant setting. 1. Subject was using immunosuppressive medications within 14 days before Screening with the exception of topical (intranasal, inhaled, and local injection), systemic (prednisone equivalent 10 mg/day or less), or as needed for hypersensitivity reactions such as computed tomography (CT) scan premedication. 2. Subject has active infections or other serious underlying significant medical illness, abnormal and clinically significant laboratory findings or psychiatric illness/social situation. 3. Subject is using a pacemaker, implantable cardiac defibrillator, neurostimulator, cochlear implants, cochlear implants, or other electronic medical equipment. 4. Subject has documented immunodeficiency or organ transplant. 5. Subject has an untreated central nervous system disease, leptomeningeal disease or cord compression. 6. Subject has a history, or presence, of significant cardiovascular diseases; including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months before randomization, congestive heart failure > New York Heart Association Class II, severe peripheral vascular disease, corrected QT (QTc) prolongation >470 msec, clinically significant pericardial effusion. 7. Subject has a history or presence of documented inflammatory bowel disease. 8. Subject is known to be positive for human immunodeficiency virus infection. -

Key
• Has SARS-CoV-2-positive antigen or molecular diagnostic test (by validated SARS-CoV-2 antigen, RT-PCR, or other molecular diagnostic assay, using an appropriate sample such as NP, nasal, oropharyngeal [OP], or saliva) ≤72 hours prior to randomization. A historical record of positive result from test conducted ≤72 hours prior to randomization is acceptable
• Meets 1 of the following 2 criteria: 1. Symptomatic Cohort (All Phases): Has symptoms consistent with COVID-19, as determined by the investigator, with onset ≤7 days before randomization or 2. Asymptomatic Cohort (Phase 2): Meets all of the following:
• Has had no symptoms consistent with COVID-19 (as determined by the investigator) occurring at any time <2 months prior to randomization
• Has had no positive SARS-CoV-2 test results from a sample collected >7 days prior to randomization
• Has had no known contact (of any duration) with an individual who has confirmed COVID-19 or confirmed positive SARS-COV-2 test result >14 days prior to randomization.
• Has experienced COVID-19 symptoms for <7 days
• Has symptoms consistent with COVID-19, as determined by investigator, with onset ≤7 days before randomization Key
• Has been admitted to a hospital prior to randomization, or is hospitalized (inpatient) at randomization, due to COVID-19
• Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, monoclonal antibodies (mAbs) against SARS-CoV-2, or intravenous immunoglobulin (IVIG) within 3 months or less than 5 half-lives of the investigational product (whichever is longer) prior to the screening visit
• Prior, current, or planned future use of any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2, IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 EUA approved treatments, where prior use is defined as the past 30 days or less than 5 half-lives of the investigational product (which is longer) from screening NOTE: Other Protocol defined Inclusion/Exclusion criteria apply

• Patients must have been assigned to S1900B based on biomarker analysis of tissue and/or blood and determined to have RET fusion-positive NSCLC as defined here:
• Patients must have RET fusion-positive NSCLC as determined by the Foundation Medicine (FMI) tissue-assay, other tumor-based assays such as next-generation sequencing (NGS), polymerase chain reaction (PCR), or follicular in situ hybridization (FISH), or by cfDNA blood assay. Patients with RET fusions detected by immunohistochemistry (IHC) alone are not eligible. The testing must be done within a laboratory with Clinical Laboratory Improvement Act (CLIA), International Organization for Standardization (ISO/International Electrotechnical Commission (IEC), College of American Pathologists (CAP), or similar certification. Presence of RET fusions detected on tests performed outside of LUNGMAP must have been confirmed by the study biomarker review panel
• For patients whose prior therapy was for stage IV or recurrent disease, the patient must have received at least one line of a platinum-based chemotherapy regimen. For patients whose prior systemic therapy was for stage I-III disease only (i.e. patient has not received any treatment for stage IV or recurrent disease), disease progression on platinum-based chemotherapy must have occurred within one year from the last date that the patient received that therapy. Prior anti-PD-1/PD-L1 therapy, alone or in combination (e.g. nivolumab, pembrolizumab, or durvalumab) is allowed
• Patients must be negative for all additional validated oncogenic drivers that could cause resistance to LOXO-292 treatment. This includes EGFR sensitizing mutations, EGFR T790M, ALK gene fusion, ROS1 gene fusion, KRAS activating mutation, BRAF V600E mutation and MET exon 14 skipping mutation or high-level amplification and expression
• Note: EGFR, ALK, ROS, KRAS, and BRAF testing is performed as part of the LUNGMAP screening/pre-screening FoundationOne test. If prior data is not available, results from the FMI testing must be obtained prior to sub-study registration
• Patients must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI). The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to sub-study registration. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to sub-study registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form. Patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration. CT and MRI scans must be submitted for central review via transfer of images and data (TRIAD)
• Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to sub-study registration
• Patients with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to registration
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration
• Patients with known human immunodeficiency virus (HIV) infection are eligible, provided they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to registration
• Patients must be able to swallow capsules
• Patients must have progressed (in the opinion of the treating physician) following the most recent line of therapy
• Patients must have recovered (=< grade 1) from any side effects of prior therapy. Patients must not have received any radiation therapy within 14 days prior to sub-study registration
• Absolute neutrophil count (ANC) >= 1,500/mcl (obtained within 28 days prior to sub-study registration)
• Platelet count >= 100,000 mcl (obtained within 28 days prior to sub-study registration)
• Serum bilirubin =< institutional upper limit of normal (IULN) (within 28 days prior to sub-study registration). For patients with liver metastases, bilirubin must be =< 5 x IULN
• Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN (within 28 days prior to sub-study registration) (if both ALT and AST are done, both must be =< 2 IULN). For patients with liver metastases, bilirubin and either ALT or AST must be =< 5 x IULN (if both ALT and AST are done, both must be =< 5 x IULN)
• Serum creatinine =< the IULN or calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault formula (within 28 days prior to sub-study registration)
• Patients must have Zubrod performance status 0-1 documented within 28 days prior to sub-study registration
• Pre-study history and physical exam must be obtained within 28 days prior to sub-study registration
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
• Patients must have electrolytes and blood urea nitrogen (BUN) performed within 14 days prior to sub-study registration
• Patients must agree to have blood specimens submitted for circulating tumor DNA (ctDNA)
• Patients must also be offered participation in banking and in the correlative studies for collection and future use of specimens
• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
• Patients with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)
• Patients must not have received any prior treatment with selective anti-RET inhibitors (anti-RET multikinase inhibitors are permitted)
• Patient must not have leptomeningeal disease, spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment, and prior to registration, AND (2) patient has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to sub-study registration
• Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 14 days prior to sub-study registration
• Patients must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable
• Patient must not have had a major surgery within 14 days prior to sub-study registration. Patient must have fully recovered from the effects of prior surgery in the opinion of the treating investigator
• Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., patients with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia
• Patients must not have a QT interval by Fridericia (QTcF) > 470 msec based on the electrocardiogram (ECG) within 28 days prior to registration. It is suggested that a local cardiologist review the QTcF intervals
• Patients must not have any clinically significant uncontrolled systemic illness, including but not limited to uncontrolled infection, requiring intravenous antibiotics, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmias, uncontrolled hypertension, or uncontrolled diabetes mellitus
• Uncontrolled diabetes: Patients who have a diagnosis of diabetes must have an hemoglobin (Hb) A1C < 7% within 28 days prior to registration. The same criterion will be used in patients with confirmed diagnosis of diabetes mellitus who have been on a stable dietary or therapeutic regimen for this condition in the last three months
• Uncontrolled blood pressure and hypertension: All blood pressure measurements within the 28 days prior to registration must be systolic blood pressure (SBP) =< 180 and diastolic blood pressure (DBP) =< 100. An exception can be made by a healthcare provider for a patient with a single blood pressure elevation who upon rechecking has a blood pressure within the parameters above
• Patients must not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of LOXO-292 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or active peptic ulcer disease)
• Patients must not be planning to receive any strong inhibitors or inducers of CYP3A4 at least 14 days prior to sub-study registration and throughout protocol treatment
• Patients must not be planning to use proton pump inhibitors (PPIs) at least one week prior to sub-study registration and throughout protocol treatment
• Patients must not be pregnant or nursing. Women study patients of reproductive potential and fertile men study patients and their partners must abstain or use effective contraception (including barrier method) while receiving study treatment and for at least 3 months after the last dose of LOXO-292. Male study patients must agree not to donate sperm for 6 months after the last dose of LOXO-292. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

Key 1. Male patients ≥18 years of age 2. Histologically or cytologically confirmed adenocarcinoma of the prostate 3. Progressive metastatic castrate-resistant prostate cancer (mCRPC): 1. Serum testosterone levels less than 50 ng/dL (or ≤0.50 ng/mL or 1.73 nmol/L) within 28 days prior to start of study drug 2. Radiographic evidence of metastatic disease 3. Disease progression on the prior systemic regimen 4. Must have received at least 2 prior systemic therapies approved for mCRPC 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6. Adequate bone marrow function 7. Able to read, understand and provide written informed consent Key 1. Previously treated or current brain metastases 2. Untreated spinal cord compression. Participants must be neurologically stable off steroids for at least 4 weeks prior to first dose of study drug 3. Concurrent treatment with anti-tumor necrosis factor (TNF) alpha therapies, systemic corticosteroids (prednisone dose >10 mg per day or equivalent), or other immune suppressive drugs within the 2 weeks prior to first dose of study drug 4. History of or known or suspected autoimmune disease (exception(s): patients with vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism that is clinically euthyroid at Screening are allowed) 5. History of clinically significant cardiovascular disease such as symptomatic congestive heart failure (CHF), myocardial infarction within 6 months before first dose of study drug, history of thromboembolic event within 3 months before first dose of study drug 6. Known active or chronic hepatitis B or hepatitis C as demonstrated by hepatitis B surface antigen (HBsAg) positivity and/or anti-hepatitis C virus (HCV) positivity, respectively, or known history of human immunodeficiency virus (HIV) seropositive status 7. Clinically active liver disease, including liver cirrhosis that is Child-Pugh class B or C 8. Second primary malignancy that has not been in remission for at least 3 years.

• Histologically-confirmed transitional cell carcinoma of the urothelium of the upper or lower urinary tract
• Recurrent or progressing stage IV disease, or surgically unresectable, recurrent or progressing disease
• Documented central FGFR genetic alteration (FGFR1, FGFR2, or FGFR3 mutations and rearrangements/ fusions )
• Measurable disease per RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
• Adequate bone marrow, liver and renal function
• Receipt of chemotherapy, targeted therapies, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or at least 5 half-lives of the drug whichever is longer before the first dose of study drug.
• Concurrent evidence of any clinically significant corneal or retinal disorder
• Phosphatemia greater than institutional upper limit of normal (ULN) at screening
• Uncontrolled tumor-related hypercalcemia

• Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent in the participant's parent trial BAT117213 (NCT01899703) or 201000 (NCT02966834)
• Participants with a diagnosis of PBC and a history of associated pruritus as evidenced by randomization into a prior eligible linerixibat clinical trial.
• Participants must have completed the main treatment period in a prior eligible linerixibat clinical trial.
• Male or female; Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Contraception by male participants or male partners of female participants is not required in this protocol.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1. is not a woman of childbearing potential (WOCBP) or 2. is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1 percent [%] per year), with low user dependency, as described during the intervention period and for at least 4 weeks, after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention; 3. a WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention; 4. if a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. 5. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Capable of giving signed informed consent as described in which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Screening total bilirubin >2x upper limit of normal (ULN). Total bilirubin >2x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%.
• Screening ALT or AST >6x ULN.
• Screening eGFR <45 milliliters per minute per 1.73 square meter (mL/min/1.73m^2) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy or ascites).
• Presence of actively replicating viral hepatitis B or C (HBV, HCV) infection and/or confirmed hepatocellular carcinoma or biliary cancer.
• Recent or current clinically significant diarrhea in the Investigator's medical opinion.
• Current symptomatic cholelithiasis or inflammatory gallbladder disease is exclusionary. Participants with history of cholecystectomy >=3 months before screening may be eligible for enrollment.
• Current diagnosis or previous diagnosis of colorectal cancer.
• Any current medical condition (e.g. psychiatric disorder, senility or dementia), which may affect the participant's ability to comply with the protocol specified procedures.
• Use of Obeticholic acid: within 8 weeks prior to the date of the screening visit and may not restart until after the end of the study or study withdrawal.
• Administration of any other ileal bile acid transporter (IBAT) inhibitor in the 1 month prior to screening.
• Current enrollment or participation in any other clinical study (except for 201000) involving an investigational study treatment within 8 weeks prior to the screening visit.
• QT interval corrected (QTc) >480 millisecond (msec): A QTc >480 msec (12-lead electrocardiogram [ECG]) at screening is exclusionary.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (~240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 measure (25 mL) of spirits.

• Ipsilateral intact biopsy-proven breast cancer clinical stage T1-T4 (by imaging)
• Available mammography and ultrasound imaging of the existing index cancer, with orthogonal measurements
• Prior history of ipsilateral or contralateral breast cancer, presenting with a new primary or recurrent disease
• Patients who were determined to be candidates for either neoadjuvant chemotherapy or neoadjuvant endocrine therapy by the treating physician
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for days following completion of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• History of ipsilateral mastectomy
• Women who already started neoadjuvant chemotherapy or endocrine therapy
• Woman who may be pregnant or nursing an infant
• Prior history of anaphylactic or anaphylactoid reaction to any contrast.
• Prior allergy to iodine or iodinated contrast.
• Impaired renal function measured by estimated glomerular filtration rate (eGFR) < 60 milliliters per minute.
• Patients with known distant metastasis.

1. Birth to <18 years of age; AND 2. Positive nucleic acid test for SARS-CoV-2 within the past 7 days; AND 3. Hospitalized, <72 hours post-admission; AND 4. One or more signs and/or symptoms of COVID-19 illness within the past 72 hours, as follows: 1. Cough; OR 2. Fever (oral temperature >100.4°F/38°C); OR 3. Chest pain; OR 4. Shortness of breath; OR 5. Myalgia; OR 6. Acute unexplained loss of smell or taste; OR 7. New/increased supplemental oxygen requirement; OR 8. Acute respiratory failure requiring non-invasive or invasive ventilation; OR 9. Encephalitis. An individual who meets any of the following criteria will be excluded from participation in this study: 1. Receiving therapeutic anticoagulation for treatment of a thromboembolic event diagnosed within the past 12 weeks; OR 2. Clinical-relevant bleeding (see criteria under Primary Outcome, below) within the past 72 hours; OR 3. Platelet count <50,000/µL within the past 24 hours; OR 4. Prothrombin time (PT) ≥2 seconds above the upper limit of age-appropriate local reference range within the past 24 hours; OR 5. Activated partial thromboplastin time (aPTT) ≥4 seconds above the upper limit of age-appropriate local reference range within the past 24 hours; OR 6. Fibrinogen level <75 mg/dL; OR 7. Severe renal impairment, as defined by estimated glomerular filtration rate (eGFR) <31 mL/min/ 1.73 m2, as calculated by the Schwartz formula; OR 8. Parent or legally authorized representative unwilling to provide informed consent for patient participation.

• First diagnosis of malignant neoplasm (International Classification of Diseases for Oncology [ICD-O] behavior code of "3") in first and continuous remission at the time of enrollment
• Curative cancer treatment must have included chemotherapy and/or radiation
• Note: Childrens Oncology Group (COG) therapeutic trial participation is not required
• All cancer treatment must have been completed within 3-36 calendar months prior to enrollment
• Patients must have a life expectancy of > 1 year
• Self-report of < 420 minutes of moderate-to-vigorous physical activity per week as assessed via the study-specific Physical Activity Worksheet
• Note: See COG Study Web Page for the Godin-Shephard Leisure Time Physical Activity Questionnaire or link to online calculator
• Ambulatory and no known medical contraindications to increasing physical activity
• No known significant physical or cognitive impairment that would prevent use of the electronic devices used for the protocol intervention (e.g. Fitbit, smartphone, tablet, or computer)
• Able to read and write English
• All patients and/or their parents or legal guardians must sign a written informed consent
• Note: Informed consent may be obtained electronically/online if allowed by local site policy and Institutional Review Board (IRB)/Research Ethics Board (REB) of record
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Post-menarchal female patients who are pregnant or planning to become pregnant in the next year are excluded
• Note: Pregnancy status can be established by clinical history with patient. Post-menarchal female patients are eligible as long as they agree to use an effective contraceptive method (including abstinence) during study participation
• Patients with previous hematopoietic stem cell transplant (HSCT) are excluded

Key
• Diagnosed with PNH
• 18 to 65 years of age
• Have received at least one RBC transfusion within last 12 weeks
• Anemia with adequate reticulocytosis
• Must be on a stable regimen of eculizumab
• Platelet count ≥ 40,000/μL without the need for platelet transfusions
• Documentation of vaccination for N. meningitidis, H. influenza, and S. pneumoniae or willingness to receive vaccinations based on local guidelines
• Willingness to receive antibiotic prophylaxis
• Female participants must use highly effective birth control to prevent pregnancy during the clinical trial and for 30 days after their last dose of study drug.
• Male participants must use a highly effective birth control with a female partner to prevent pregnancy during the clinical trial and for 90 days after the last dose of study drug. Key
• Current evidence of bone marrow failure or aplastic anemia requiring treatment
• History of a major organ transplant or hematopoietic stem cell/marrow transplant
• Received another investigational agent within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater
• Documented C5 mutations
• Known or suspected complement deficiency
• Contraindication to any of the required vaccinations
• Active bacterial infection or clinically significant active viral infection, a body temperature >38°C, or other evidence of infection
• History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection
• History of hypersensitivity reactions to commonly used antibacterial agents NOTE: Additional inclusion/exclusion criteria may apply, per protocol.

• Subjects with moderate hemophilia A (baseline factor VIII activity 1-5%) or severe hemophilia A (baseline factor VIII activity <1%) on prophylactic standard half-life FVIII infusions OR subjects with moderate or severe hemophilia A who have not started prophylactic treatment
• Less than 18 years of age
• Subjects with documented FVIII inhibitor
• Subjects with a history of ≥ 2 target joints
• Subjects with a history of synovectomy
• Currently using medications known to impact bone and mineral metabolism (e.g., bisphosphonates, corticosteroids, estrogen, testosterone, calcitonin, thyroid hormone therapy);
• Disease states known to affect bone integrity (e.g., primary hyperparathyroidism, Paget's disease, clinically significant liver disease)

PRE-REGISTRATION:
• Pathology: Histologic or cytologic proof of pancreatic adenocarcinoma or adenosquamous carcinoma
• TNM Stage: Tx-4, N0-1, M0 (M0 disease does not include spread to distant lymph nodes and organs)
• Resectable Primary Tumor: Local radiographic reading must be consistent with resectable disease defined as the following on 1) arterial and venous phase contrast-enhanced abdominal/pelvic CT scan or abdominal/pelvic magnetic resonance imaging (MRI) scan and 2) chest CT:
• No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery (if applicable)
• Less than 180 degree interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence
• No evidence of metastatic disease
• Measurable disease or non-measurable disease o Non-measurable disease is defined as cytologic or histologic confirmation of adenocarcinoma of adenosquamous carcinoma by fine needle aspiration or core-biopsy of the pancreas without measurable disease by radiographic imaging REGISTRATION:
• Confirmation of resectable disease by real-time central imaging review by the Alliance Imaging Core Lab at Imaging and Radiation Oncology Core (IROC) Ohio
• Determined to be appropriate candidate for curative-intent pancreatectomy by surgeon intending to perform the resection
• No prior radiation therapy, chemotherapy, targeted therapy, investigational therapy, or surgery for pancreatic cancer
• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.
• Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Total Neuropathy Score < 2
• Absolute neutrophil count (ANC) >= 1,500/uL
• Platelet count >= 100,000/uL
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (If obstructive jaundice is present, then biliary drainage must be initiated and total bilirubin =< 3.0)
• Creatinine =< 1.5 x ULN OR calculated (Calc.) creatinine clearance >= 30 mL/min (Calculated using the Cockcroft-Gault equation)
• No known Gilbert's Syndrome or known homozygosity for UGAT1A1*28 polymorphism
• No comorbid conditions that would prohibit curative-intent pancreatectomy
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration
• Chronic concomitant treatment with strong inducers of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inducers must discontinue the drug prior to registration

Inclusion Criteria (non-burned individuals):
• Healthy male and female subjects
• 18-65 years of age.
• Free of any underlying medical conditions Exclusion Criteria (non-burned individuals):
• Any burn-related injuries resulting in at least one night of hospitalization.
• Heart disease or any other chronic medical condition requiring regular medical therapy including cancer, diabetes, and hypertension.
• Abnormalities detected on routine screening
• Individuals who participate in a structured aerobic exercise training program at moderate to high intensities.
• Current smokers, as well as individuals who regularly smoked within the past 3 years.
• Body mass index of greater than 30 kg/m^2.
• Pregnant individuals Inclusion Criteria (burn survivors):
• Healthy male and female subjects
• 18-65 years of age.
• Free of any underlying medical conditions
• Having a burn injury covering 20-40% or >40% of the participant's body surface area; at least 50% of those burn injuries must be full thickness that required skin grafting.
• Participants must have been hospitalized due to the burn injury for a minimum of 15 days Exclusion Criteria (burn survivors):
• Any burn-related injuries resulting in at least one night of hospitalization.
• Heart disease or any other chronic medical condition requiring regular medical therapy including cancer, diabetes, and hypertension.
• Abnormalities detected on routine screening
• Individuals who participate in a structured aerobic exercise training program at moderate to high intensities.
• Current smokers, as well as individuals who regularly smoked within the past 3 years.
• Body mass index of greater than 30 kg/m^2.
• Pregnant individuals
• Extensive unhealed injured skin