Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors
The purpose of this study is to find out whether the study drug, LY4101174, is safe, tolerable and effective in participants with advanced, or metastatic solid tumors. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.
* Have one of the following solid tumor cancers:
* Cohort A1: urothelial carcinoma, triple negative breast cancer, non-small cell lung cancer, esophageal cancer, pancreatic cancer, ovarian cancer, cervical cancer (squamous cell carcinoma), head and neck squamous cell carcinoma or prostate cancer
* Cohort A2/B1/B2: urothelial carcinoma
* Cohort C1: triple negative breast cancer
* Cohort C2: non-small cell lung cancer
* Cohort C3: ovarian or fallopian tube cancer
* Cohort C4: cervical cancer
* Cohort C5: head and neck squamous cell carcinoma
* Prior Systemic Therapy Criteria:
* Cohort A1/C1-5: Individual has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating investigator; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies
* Cohort A2/B1/B2: Individual must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
* Prior enfortumab vedotin specific requirements:
* Cohorts A1/A2/C1-5: prior treatment with enfortumab vedotin is allowed, but not required
* Cohort B1: individual must be enfortumab vedotin naive in the advanced/metastatic setting
* Cohort B2: individual must have received enfortumab vedotin in the metastatic/advanced setting.
* Measurability of disease
* Cohort A1: measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1)
* Cohorts A2, B1, B2, C1-5: measurable disease required as defined by RECIST v1.1
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country specific regulations
Exclusion Criteria:
* Individual with known or suspected uncontrolled CNS metastases
* Individual with uncontrolled hypercalcemia
* Individual with uncontrolled diabetes
* Individual with evidence of corneal keratopathy or history of corneal transplant
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Current of history of intestinal obstruction in the previous 3 months
* Recent thromboembolic event or bleeding disorder
* Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
* History of pneumonitis/interstitial lung disease
* History of Grade ≥3 skin toxicity when receiving enfortumab vedotin
* Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention
DRUG: LY4101174
Prostate Cancer, Esophageal Cancer, Non-Small Cell Lung Cancer, Pancreatic Cancer, Bladder Cancer, Ovarian Cancer, Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Triple Negative Breast Cancer, Advanced Solid Tumor, Breast - Female, Breast - Male, Cervix, Esophagus, Larynx, Lip, Oral Cavity and Pharynx, Lung/Thoracic, Ovary, Pancreas, Prostate, Urinary Bladder, Metastatic Solid Tumor, Recurrent Solid Tumor, Urinary Bladder Neoplasm, Renal Pelvis Cancer
A Study of Disitamab Vedotin in Previously Treated Solid Tumors That Express HER2
This clinical trial is studying advanced or metastatic solid tumors. Once a solid tumor has grown very large in one spot or has spread to other places in the body, it is called advanced or metastatic cancer. Participants in this study must have head and neck squamous cell cancer, non-small cell lung cancer, endometrial cancer, or ovarian cancer. Participants must have tumors that have a marker called HER2.
This clinical trial uses an experimental drug called disitamab vedotin (DV). DV is a type of antibody-drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. In this study, all participants will get DV once every 2 weeks.
This study is being done to see if DV works to treat different types of solid tumors that express HER2. It will also test how safe the drug is for participants. This trial will also study what side effects happen when participants get the drug. A side effect is anything a drug does to your body besides treating the disease.
* Cohort 1: Head and neck squamous cell carcinoma (HNSCC)
* Pathologically-documented squamous cell carcinoma of the head and neck with primary tumor site arising from the oral cavity, oropharynx, hypopharynx, and larynx
* Unresectable locally recurrent or metastatic stage disease
* Prior therapies:
* Participants must have disease progression after treatment with a platinum-based therapy
* No more than 1 line of cytotoxic chemotherapy for advanced disease
* Cohort 2: Non-small cell lung cancer (NSCLC)
* Pathologically documented NSCLC
* Unresectable locally-advanced or metastatic stage disease
* Prior therapies
* Must have progressed during or after a platinum-based therapy or, within 6 months of platinum-based adjuvant, neoadjuvant, or concomitant chemoradiotherapy for early or locally-advanced stage disease
* Must have received prior anti-PD(L)1 therapy, unless contraindicated
* No more than 2 prior lines of cytotoxic chemotherapy for advanced disease
* Cohort 3: Ovarian Cancer
* Pathologically documented epithelial cancers of ovarian, fallopian tube, or peritoneal origin
* Unresectable locally-advanced or metastatic stage disease
* Prior therapies
* Must have platinum resistant disease (6 months or less between the completion of platinum-based treatment and identification of recurrence)
* Must not have received more than 4 lines of prior cytotoxic chemotherapies for advanced disease
* May have received prior anti-PD(L)1 therapy
* Cohort 4: Endometrial Cancer
* Must have pathologically documented adenocarcinoma of the endometrium
* Must have unresectable locally-advanced or metastatic stage disease.
* Prior therapies
* Must have relapsed/progressed after at least one prior platinum-based chemotherapy for recurrent, metastatic or primary unresectable disease
* Must not have received more than 3 lines of prior cytotoxic chemotherapies for advanced disease
* May have received prior anti-PD(L)1 therapy
* HER2 expression of 1+, 2+, or 3+, as determined by local IHC testing on a fresh or archival tumor tissue. Note: Participants with HER2 mutations are eligible.
* Measurable disease per RECIST v1.1 criteria as assessed by the investigator
* Able to provide formalin-fixed, paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides)
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
Exclusion Criteria:
* Prior treatment with an MMAE-containing agent.
* Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin.
* History of another invasive malignancy within 2 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
* Active untreated CNS or leptomeningeal metastasis
DRUG: disitamab vedotin
Carcinoma, Squamous Cell of Head and Neck, Carcinoma, Non-Small-Cell Lung, Ovarian Neoplasms, Endometrial Neoplasms
A Safety, Tolerability and Efficacy Study of NC410 Plus Pembrolizumab in Participants With Advanced Unresectable or Metastatic Solid Tumors
This is an open-label, non-randomized, Phase 1b/2 study to determine the safety and tolerability of NC410 when combined with a standard dose of pembrolizumab. This study will also assess the clinical benefit of combination therapy in participants with advanced unresectable and/or metastatic ICI refractory solid tumors OR ICI naïve MSS/MSI-low solid tumors
* Be 18 years of age on day of signing informed consent.
* Participant with histologically or cytologically confirmed diagnosis of the following advanced unresectable and/or metastatic solid tumors:
* Phase 1b: Participants with solid tumors that are known to be associated as MSS/MSI-low in the majority including: CRC (without liver metastasis), Gastric including GE junction, Esophageal, Ovarian, and H\&N cancer (regardless of prior treatment with ICIs). Note: Participants must have had disease progression after at least one line of systemic standard of care therapy prior to enrollment. Participants who discontinue standard treatment due to intolerance or refuse standard treatment will also be eligible to enroll.
* Phase 2 ICI Refractory Solid Tumors (Cohort 1): Participants with solid tumors including CRC, Gastric including GE junction, Esophageal, Endometrial, H\&N, Lung, Cervical and Ovarian cancer.Participants must have progressed on treatment with an anti-PD1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
* Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
* Has demonstrated disease progression after PD-1/L1 as defined by RECIST v1.1.
* Phase 2 ICI naïve Solid Tumors (Cohorts 2a-2c):Tumors known to be associated with MSS/MSI-low status such as CRC, Gastric including GE junction, and Ovarian cancer where participants have not been previously treated with ICIs. Note: Participants must have had disease progression after at least one line of systemic standard of care therapy prior to enrollment. Participants who discontinue standard treatment due to intolerance or refuse standard treatment will also be eligible to enroll. Note: Confirmation of MSS/MSI status should be assessed prior to study entry (either by historical result or during screening).
* A male participant must agree to use contraception and refrain from sperm donation or expecting to father a child, from Screening through the treatment period and for at least 120 days after the last dose of study treatment.
* A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
* Not a woman of childbearing potential (WOCBP)
* A WOCBP who agrees to follow contraceptive guidance outlined in the protocol from Screening through the treatment period and for at least 120 days after the last dose of study treatment.
* Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Able to provide tumor tissue sample at Screening, archival (≤ 5 years old) or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
* Life expectancy greater than or equal to 12 weeks as judged by the Investigator.
* Have adequate organ function as defined in the protocol.
Exclusion Criteria:
* A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137), and was discontinued from that treatment due to a Grade 3 or higher irAE.
* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to treatment. Note: Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤ 2 requiring treatment or hormone replacement may be eligible. If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
* Has received prior radiotherapy within 2 weeks of start of study treatment or has had a history of radiation pneumonitis. Note: Participants must have recovered from all radiation-related toxicities and do not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
* Has received G-CSF or GM-CSF within 7 days prior to start of study treatment.
* Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
* Receipt of COVID-19 vaccine within ≤ 14 days prior to first administration of study treatments. For 2-dose COVID-19 vaccines or COVID-19 booster, participants must wait at least 14-days after administration prior to beginning study treatment.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
* Has had an allogeneic tissue/stem cell/solid organ transplant.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of bladder, that have undergone potentially curative therapy are not excluded.
* Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
* Has severe hypersensitivity (≥ Grade 3), known allergy or reaction to Pembrolizumab, NC410, and/or any of their excipients.
* Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
* Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
* Has an active infection requiring systemic therapy.
* Has a known active or history of HIV infection. No HIV testing is required unless mandated by local health authority.
* Has known active Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
DRUG: NC410, DRUG: pembrolizumab
Lung Cancer, Endometrial Cancer, Esophageal Cancer, Gastric Cancer, Ovarian Cancer, Cervical Cancer, Advanced or Metastatic Solid Tumors, Colon, Lung/Thoracic, Other Female Genital, Other Male Genital, Ovary, Pancreas, Microsatellite Instability Low, Microsatellite Instability High, Microsatellite Stable, Colo-rectal Cancer, Head Neck Cancer
A Study of ACR-368 in Ovarian Carcinoma, Endometrial Adenocarcinoma, and Urothelial Carcinoma
This is an open label Phase 1b/2 study to evaluate the efficacy and safety of ACR-368 as
monotherapy or in combination with ultralow dose gemcitabine in participants with
platinum-resistant ovarian carcinoma, endometrial adenocarcinoma, and urothelial carcinoma
based on Acrivon's OncoSignature® test status.
Inclusion Criterial: General
• Participant must be able to give signed, written informed consent.
• Participant must have histologically confirmed, locally advanced (i.e., not amenable
to curative surgery and/or radiation therapy) or metastatic cancer that has progressed
during or after at least 1 prior therapeutic regimen.
• Participant must have at least 1 measurable lesion per Response Evaluation Criteria in
Solid Tumors (RECIST) v1.1 criteria (by local Investigator) (Eisenhauer, 2009).
Participant must have radiographic evidence of disease progression based on RECIST
criteria following the most recent line of treatment. Biochemical recurrence (eg,
CA-125 in ovarian carcinoma) only is not considered as disease progression.
• Participant must be willing to provide tissue from a newly obtained tumor biopsy from
an accessible tumor lesion not previously irradiated after signed informed consent.
Newly obtained is defined as a specimen obtained up to 6 weeks prior to initiation of
treatment on Day 1 if no intercurrent systemic therapy in the interval.
• Participant must be willing to provide an archival tumor tissue block or at least 20
unstained slides, if available.
• Participant must have stabilized or recovered (Grade 1 or baseline) from all prior
therapy related toxicities, except as follows:
• Alopecia is accepted.
• Endocrine events from prior immunotherapy stabilized at ≤ Grade 2 due to need for
replacement therapy are accepted (including hypothyroidism, diabetes mellitus, or
adrenal insufficiency).
• Neuropathy events from prior cytotoxic therapies stabilized at ≤ Grade 2 are
accepted.
• Participant must have an Eastern Cooperative Oncology Group Performance Status 0 or 1.
• Participant must have an estimated life expectancy of longer than 3 months.
• Participant must have adequate organ function at Screening, defined as:
• Absolute neutrophil count > 1500 cells/µL without growth factor support within 1
week prior to obtaining the hematology values at Screening.
• Hemoglobin ≥ 9.0 g/dL without transfusion or growth factor support within 2 weeks
prior to obtaining the hematology values at Screening.
• Platelets ≥ 100,000 cells/µL without transfusion within 1 week prior to obtaining
the hematology values at Screening.
• Calculated creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft Gault
formula.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper
limit of normal (ULN); ≤ 5 × ULN if liver metastases are present.
• Total bilirubin ≤ 1.5 × ULN not associated with Gilbert's syndrome. If associated
with Gilbert's syndrome ≤ 3 x ULN is acceptable.
• Serum albumin ≥ 3 g/dL.
• Participant must have adequate coagulation profile as defined below (including if
receiving anticoagulation therapy): Prothrombin time within 1.5 x ULN. Activated
partial thromboplastin time within 1.5 x ULN. If the patient is anticoagulated, must
be on a stable dose of anticoagulant for ≥ 1 month.
Tumor Specific Inclusion Criteria
For Ovarian Carcinoma:
• Participant must have histologically documented, platinum resistant, advanced
(metastatic and/or unresectable) high-grade serous/endometrioid ovarian, primary
peritoneal, or fallopian tube cancer. Platinum-resistant disease, defined as
progression or relapse within 6 months after the completion of platinum-based therapy,
is eligible.
Platinum sensitive disease, defined as disease which progress after 6 or more months
after the completion of platinum-based therapy and primary platinum refractory
disease, defined as progression while on the upfront platinum-based therapy, is not
eligible.
a. Carcinosarcoma is eligible.
• Participant must have received at least 1 but no more than 6 prior lines of systemic
therapy, including at least 1 line of therapy containing platinum derivative and
taxane, and single-agent therapy must be appropriate as the next line of treatment:
• Participant must have had prior bevacizumab or did not receive bevacizumab based on
Investigator judgment (see Section 2.1.1).
For Endometrial Carcinoma
• Participant must have histologically documented, high-grade endometrial
adenocarcinoma.
• All Grade 3 International Federation of Gynecology and Obstetrics epithelial
endometrial histologies are eligible including: endometrioid, serous, and
clear-cell carcinoma.
• Carcinosarcoma is eligible. Enrollment of participants with this histology will
be capped at 5% for each cohort.
• Participant must have no more than 3 prior lines of therapy in the recurrent
setting, including platinum-based chemotherapy for subtypes of endometrial
adenocarcinoma where it is a standard of care.
• Participant must have documented failure or ineligibility (based on Investigator
judgement) for prior anti-programmed cell death protein 1/anti-programmed death-
ligand 1 (PD 1/PD L1) based therapy for advanced/metastatic disease. Prior combination
of PD 1/PD L1 inhibitor and vascular endothelial growth factor tyrosine kinase
inhibitor is acceptable.
For Urothelial Carcinoma
• Participant must have histologically documented, advanced (metastatic and/or
unresectable) urothelial carcinoma. Variant histology is allowed as long as the tumor
is predominantly urothelial.
• Participants must have:
• Received a platinum containing regimen (cisplatin or carboplatin) in the
metastatic/locally advanced, neoadjuvant, or adjuvant setting. If platinum was
administered in the adjuvant/neoadjuvant setting, participant must have
progressed within 12 months of completion.
• Failed or have been ineligible for checkpoint inhibitors (including PD-1 or PD-L1
inhibitors).
• Failed or have been ineligible for enfortumab vedotin.
• Have no known life-prolonging therapy available
Exclusion Criteria:
General
• Participant with known symptomatic brain metastases requiring > 10 mg/day of
prednisolone (or its equivalent). Participants with previously diagnosed brain
metastases are eligible if they have completed their treatment, have recovered from
the acute effects of radiation therapy or surgery prior to the start of ACR-368
treatment, fulfill the steroid requirement for these metastases, and are
neurologically stable based on central nervous system imaging ≥ 4 weeks after
treatment.
• Participant had a failure to recover from the reversible effects of prior anti-cancer
therapy, as follows:
• Endocrine events from prior immunotherapy at Grade > 2.
• Neuropathy events from prior cytotoxic therapies at Grade > 2.
• All other reversible effects of prior anti- cancer therapy (except alopecia) at
Grade >1 or Baseline.
• Participant had systemic therapy or radiation therapy within 2 weeks prior to the
first dose of study drug.
• Participants has known human immunodeficiency virus, hepatitis B, or hepatitis C
infection that is considered uncontrolled based on the criteria included in Appendix
• 5. Participant has a history of clinically meaningful coagulopathy, bleeding diathesis.
• Participant has cardiovascular disease, defined as:
• Uncontrolled hypertension defined as blood pressure > 160/90 mmHg at Screening
confirmed by repeat (medication permitted).
• History of torsades de pointes, significant Screening electrocardiogram (ECG)
abnormalities, including ventricular rhythm disturbances, unstable cardiac
arrhythmia requiring medication, pathologic symptomatic bradycardia, left bundle
branch block, second degree atrioventricular (AV) block type II, third degree AV
block, Grade ≥ 2 bradycardia, uncorrected hypokalemia not amenable to correction,
congenital long QT syndrome, prolonged QT interval due to medications, corrected
QT (QTc) > 450 msec (for men) or > 470 msec (for women).
• Symptomatic heart failure (per New York Heart Association guidelines; (Caraballo,
2019), unstable angina, myocardial infarction, severe cardiovascular disease
(ejection fraction < 20%, transient ischemic attack, or cerebrovascular accident
within 6 months of Day 1).
• Participant has a history of major surgery within 4 weeks of Screening.
• Participant has a history of bowel obstruction requiring decompression through a
nasogastric tube within 8 weeks of Screening. Participants has signs or symptoms of
intestinal obstruction, which include nausea, vomiting, and objective radiologic
finding of bowel obstruction.
• Participant has taken a prior cell cycle CHK1 inhibitor, including ACR-368
Tumor Specific Exclusion Criteria
For Ovarian Carcinoma:
• Participant has non-epithelial carcinoma, clear-cell, mucinous, germ-cell, low-grade
serous, or low-grade endometrioid carcinoma.
• Participant has a history of clinically meaningful ascites, defined as a history of
paracentesis or thoracentesis within 4 weeks of Screening. Participant has a planned
therapeutic paracentesis or thoracentesis between Screening and Cycle 1 Day 1 dosing.
• Participant has a history of active inflammatory bowel disease within 2 years prior to
Screening.
• Participant has a history of bowel perforation, fistula, necrosis, or leak within 8
weeks of Screening.
For Endometrial Adenocarcinoma:
• Participant has low-grade endometrioid carcinoma.
• Participant has mesenchymal tumors of the uterus.
• Participant has a history of clinically meaningful ascites, defined as a history of
paracentesis or thoracentesis within 4 weeks of Screening. Participant has a planned
therapeutic paracentesis or thoracentesis between Screening and Cycle 1 Day 1 dosing.
For Urothelial Carcinoma:
• Participant has sarcoma, carcinosarcoma, melanoma, or lymphoma of the bladder.
• Participant has not received a previous platinum-based regimen.
• Participant has small cell or neuroendocrine histology.
A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or Chemotherapy or TransCon TLR7/8 Agonist in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies (IL Believe)
TransCon IL-2 β/γ is an investigational drug being developed for treatment of locally
advanced or metastatic solid tumors. This is a first-in-human, open-label, Phase 1/2, dose
escalation and dose expansion study of TransCon IL-2 β/γ as monotherapy or in combination
therapy in adult participants with advanced or metastatic solid tumors. Given the unique PK
profile enabled by the TransCon technology, TransCon IL-2 β/γ presents the opportunity to
enhance the therapeutic index of current IL-2 therapy.
• At least 18 years of age
• Demonstrated adequate organ function at screening
• Life expectancy >12 weeks as determined by the Investigator
• At least 1 lesion of measurable disease, except for Post Anti-PD-1 Melanoma and 2L+
Cervical Cancer (at least 2 lesions of measurable disease)
• Female and male participants of childbearing potential who are sexually active must
agree to use highly effective methods of contraception
• Participants must have histologically confirmed locally advanced, recurrent, or
metastatic solid tumor malignancies that cannot be treated with curative intent
(surgery or radiotherapy), with the exception of the neoadjuvant cohorts
• Part 1 and Part 2: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1,
or 2
• Part 3: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Part 1 and Part 2: Participants who have undergone treatment with anti-PD-1,
anti-PD-L1, or anti-CTLA-4 antibody must have a washout of at least 4 weeks from the
last dose and evidence of disease progression per investigator assessment before Cycle
1 Day 1 (C1D1)
• Part 1 and Part 2: Participants who have previously received an immunotherapy prior to
C1D1 must have any immune-related toxicities resolved to ≤Grade 1 or baseline (prior
to the immunotherapy) to be eligible, with the exception of participants on well
controlled physiologic endocrine replacement
• Part 3: Part 3, neoadjuvant cohorts: participants must have completely resectable
disease
Key
Exclusion Criteria:
• Symptomatic central nervous system metastases
• Active autoimmune diseases, regardless of need for immunosuppressive treatment, with
the exception of participants well controlled on physiologic endocrine replacement
• Any uncontrolled bacterial, fungal, viral, or other infection
• Significant cardiac disease
• A marked clinically significant baseline prolongation of QT/QTc interval (e.g.,
repeated demonstration of a QTc interval >480 ms) [CTCAE Grade 1]) using Fridericia's
QT correction formula
• Positive for HIV or has known active hepatitis B or C infection
• Known hypersensitivity to any study treatment(s) used in the specific study
part/cohort
• Participants who have been previously treated with IL-2 or IL-2 variants (all
participants), or TLR agonist (Part 3 only for Post Anti-PD-1 Melanoma, 2L+ Cervical
Cancer, and Neoadjuvant Melanoma)
• Systemic immunosuppressive treatment with the exception for patients on corticosteroid
taper (for example, for chronic obstructive pulmonary disease exacerbation).
• Vaccination with live, attenuated vaccines within 4 weeks of C1D1
• Treatment with any other anti-cancer systemic treatment (approved or investigational)
or radiation therapy within 4 weeks of C1D1
• Part 3: Other active malignancies within the last 2 years
• Women who are breastfeeding or have a positive serum pregnancy test during screening
Letrozole With or Without Paclitaxel and Carboplatin in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
This phase III trial studies how well letrozole with or without paclitaxel and carboplatin
works in treating patients with stage II-IV low-grade serous carcinoma of the ovary,
fallopian tube, or peritoneum. Letrozole is an enzyme inhibitor that lowers the amount of
estrogen made by the body which in turn may stop the growth of tumor cells that need estrogen
to grow. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different
ways to stop the growth of tumor cells, either by killing the cells, by stopping them from
dividing, or by stopping them from spreading. It is not yet known whether giving letrozole
alone or in combination with paclitaxel and carboplatin works better in treating patients
with low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum compared to
paclitaxel and carboplatin without letrozole.
• Patients must have newly diagnosed, stage II-IV low-grade serous ovarian cancer
(submission of pathology report[s] required). Ovarian cancer = ovarian, fallopian tube
and primary peritoneal cancers
• NOTE: Patients with a prior history of serous borderline tumors but a new
diagnosis of stage II-IV low-grade serous ovarian cancer are eligible
• p53 immunohistochemistry (IHC) is required and must show nonaberrant pattern
(nonaberrant p53 expression is consistent with normal/wildtype TP53)
• A copy of the pathology report that includes the diagnosis of low grade
serous ovarian cancer and nonaberrant p53 IHC result must be submitted in
RAVE. NOTE: If aberrant p53 expression is found on p53 IHC, the patient is
NOT eligible (aberrant p53 expression is consistent with mutant TP53 and
supports diagnosis of high grade serous ovarian cancer)
• Appropriate stage for study entry based on the following diagnostic workup:
• History/physical examination within 14 days prior to registration;
• Radiographic tumor assessment within 28 days prior to registration. (23-MAY-2023)
• Age >= 18
• Patients must have undergone an attempt at maximal upfront cytoreductive surgery, with
either optimal (=< 1 cm diameter residual disease/nodule) or suboptimal residual
disease (> 1 cm diameter residual disease/nodule) status allowed
• Patients must have undergone a bilateral salpingo-oophorectomy
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0, 1 or 2 within 14 days prior to registration
• Patients must be within =< 8 weeks of primary cytoreductive surgery at time of
randomization
• Patients must be able to take per oral (P.O.) medications
• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl (within 14 days
prior to registration)
• Platelets greater than or equal to 100,000 cells/mcl (within 14 days prior to
registration)
• Creatinine less than or equal to 1.5 x upper limit of normal (ULN) (within 14 days
prior to registration)
• Bilirubin less than or equal to 1.5 x ULN (within 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal
to 3 x ULN (within 14 days prior to registration)
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
Exclusion Criteria:
• Patients may not have received neoadjuvant or adjuvant chemotherapy or radiotherapy
for the treatment of this disease
• Patients may not have received previous hormonal therapy for the treatment of this
disease
• Patients with known hypersensitivity to letrozole or hypersensitivity/intolerance to
carboplatin/paclitaxel therapy
• Patients with severe cardiac disease:
• Myocardial infarction or unstable angina within 6 months prior to registration
• New York Heart Association (NYHA) class II or greater congestive heart failure
• Patients with known central nervous system metastases
• Patients with active (except for uncomplicated urinary tract infection) or
uncontrolled systemic infection
• Patients with >= grade 2 baseline neuropathy
• Known human immunodeficiency virus (HIV)-infected patients on effective
anti-retroviral therapy with undetectable viral load within 6 months are eligible for
this trial
Ovary, Low Grade Fallopian Tube Serous Adenocarcinoma, Primary Peritoneal Low Grade Serous Adenocarcinoma, Stage II Fallopian Tube Cancer AJCC v8, Stage II Ovarian Cancer AJCC v8, Stage II Primary Peritoneal Cancer AJCC v8, Stage III Fallopian Tube Cancer AJCC v8, Stage III Ovarian Cancer AJCC v8, Stage III Primary Peritoneal Cancer AJCC v8, Stage IV Fallopian Tube Cancer AJCC v8, Stage IV Ovarian Cancer AJCC v8, Stage IV Primary Peritoneal Cancer AJCC v8, Ovarian Low Grade Serous Adenocarcinoma
UT Southwestern; Parkland Health & Hospital System
Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
This phase III trial studies how well active surveillance help doctors to monitor subjects with low risk germ cell tumors for recurrence after their tumor is removed. When the germ cell tumor has spread outside of the organ in which it developed, it is considered metastatic. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The trial studies whether carboplatin or cisplatin is the preferred chemotherapy to use in treating metastatic standard risk germ cell tumors.
* There is no age limit for the low risk stratum (stage I ovarian immature teratoma and stage I non-seminoma or seminoma malignant GCT \[all sites\])
* Standard risk 1: Patients must be \< 11 years of age at enrollment
* Standard risk 2: Patients must be \>= 11 and \< 25 years of age at enrollment
* Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I germ cell tumor; for the standard risk arms, patients must be newly diagnosed with metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary extracranial germ cell tumor in any of the categories outlined below is required of all patients at enrollment except for those who were initially diagnosed with stage I non-seminoma malignant GCT and later recur during observation post surgery off study; for these patients, if elevated tumor markers rise to \> 5 x upper limit of normal (ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is not required for enrollment
* Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB; grade: 2 or 3; histology: pure immature teratoma (may contain microscopic foci of yolk sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT); tumor markers: alpha-FP =\< 1,000 ng/mL, beta-HCG institutional normal; all ages
* Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage: COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA, IB and IS; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
* Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular stage IA IB, and IS; histology: may contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
* Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus Classification \[IGCCC\] criteria DO NOT apply); histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \< 11
* Standard risk 2 (SR2)
* Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \>= 11 and \< 25
* Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; tumor markers: must be IGCCC good risk; post op: alpha-FP \< 1,000 ng/mL, beta-HCG \< 5,000 IU/mL and lactate dehydrogenase (LDH) \< 3.0 x normal; age (years) \>= 11 and \< 25
* Site: extragonadal; stage: COG stage II; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) \>= 11 and \< 25
* Notes:
* IGCCC criteria only apply to SR2 patients with a testicular primary tumor
* Use post-op tumor marker levels to determine IGCCC risk group
* Stage 1 seminoma patients are not eligible for the standard risk arms of the study
* For the low risk stage I non-seminoma MGCT and the standard risk arms, components of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the only malignant component present, then it must be deemed by the pathologist to be greater than a "microscopic component" of yolk sac tumor
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients)
* Adequate renal function defined as:
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR
* A serum creatinine based on age/gender as follows (within 7 days prior to enrollment): (mg/dL)
* 1 month to \< 6 months male: 0.4 female: 0.4
* 6 months to \< 1 year male: 0.5 female: 0.5
* 1 to \< 2 years male: 0.6 female: 0.6
* 2 to \< 6 years male: 0.8 female: 0.8
* 6 to \< 10 years male: 1 female: 1
* 10 to \< 13 years male: 1.2 female: 1.2
* 13 to \< 16 years: male: 1.5 female: 1.4
* \>= 16 years male: 1.7 female: 1.4
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT is 45 U/L) (within 7 days prior to enrollment)
* Peripheral absolute neutrophil count (ANC) \>= 1,000/mm\^3 (within 7 days prior to enrollment) AND
* Platelet count \>= 100,000/mm\^3 (within 7 days prior to enrollment)
* Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
* Eligibility criteria to participate in the pilot study of the AYA-Hears instrument (patient reported outcomes \[PROs\] of ototoxicity) Note: participants in group 1 will not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be enrolled on the AGCT1531 SR2 arm in order to participate
* \>= 11 and \< 25 years old at enrollment
* Able to fluently speak and read English
* Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy including diagnoses other than germ cell tumor
* Followed for cancer or survivorship care at one of the following institutions:
* Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
* Dana Farber/Harvard Cancer Center
* Hospital for Sick Children
* Children's Hospital of Eastern Ontario
* Oregon Health and Science University
* Seattle Children's Hospital
* Yale University
Exclusion Criteria:
* Patients with any diagnoses not listed including:
* Stage I testicular cancer patients who have undergone primary RPLND (retroperitoneal lymph node dissection)
* Pure dysgerminoma
* Pure mature teratoma
* Pure immature teratoma COG stage I, grade I
* Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) \>= 1000 ng/mL
* Pure immature teratoma COG stage II - IV or FIGO stage IC to IV
* "Poor risk" GCT (age \>= 11 years old and COG stage IV ovarian, COG stage III or IV EG, or IGCCC intermediate or poor risk testicular), or
* Primary central nervous system (CNS) germ cell tumor
* Germ cell tumor with somatic malignant transformation
* Spermatocytic seminoma
* Patients must have had no prior systemic therapy for the current cancer diagnosis
* Patients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain \[stage IV disease\] would be considered poor risk and therefore not eligible for this trial)
* Patients with significant, pre-existing co-morbid respiratory disease that contraindicate the use of bleomycin are ineligible for the standard risk arms of the trial
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
* Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation; (this criteria applies ONLY to patients who will receive chemotherapy \[SR1 and SR2 patients\])
Childhood Extracranial Germ Cell Tumor, Malignant Germ Cell Tumor, Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Stage I Ovarian Choriocarcinoma, Stage II Ovarian Choriocarcinoma, Stage III Ovarian Choriocarcinoma, Stage IV Ovarian Choriocarcinoma, Testicular Mixed Choriocarcinoma and Embryonal Carcinoma, Testicular Mixed Choriocarcinoma and Teratoma, Testicular Mixed Choriocarcinoma and Yolk Sac Tumor, Stage I Testicular Choriocarcinoma AJCC v6 and v7, Stage I Testicular Embryonal Carcinoma AJCC v6 and v7, Stage I Testicular Yolk Sac Tumor AJCC v6 and v7, Stage II Testicular Choriocarcinoma AJCC v6 and v7, Stage II Testicular Embryonal Carcinoma AJCC v6 and v7, Stage II Testicular Yolk Sac Tumor AJCC v6 and v7, Stage III Testicular Choriocarcinoma AJCC v6 and v7, Stage III Testicular Embryonal Carcinoma AJCC v6 and v7, Stage III Testicular Yolk Sac Tumor AJCC v6 and v7, Malignant Ovarian Teratoma, Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage I Ovarian Teratoma AJCC v6 and v7, Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Other Female Genital, Other Male Genital, Ovary, Unknown Sites, Stage I Testicular Seminoma AJCC v6 and v7
UT Southwestern; Children’s Health; Parkland Health & Hospital System
Use of the CA 125 Algorithm for the Early Detection of Ovarian Cancer in Low Risk Women
The goal of this clinical research study is to evaluate a method involving 4 blood tests called CA-125, HE4, HE4 antigen autoantibody complexes, and osteopontin that may be helpful in the early detection of ovarian cancer in women who are at low risk.
• Female, \>/= 50 years old or less than 75 years old.
• Postmenopausal (\>/= 12 months amenorrhea).
• Have at least one ovary.
• Cancer-free and have not received any chemotherapy or radiation therapy for \>/=12 months prior to enrolling on this study.
• Willingness to return for CA 125 blood tests annually or earlier if indicated.
• Willingness to return to undergo transvaginal ultrasound if indicated.
• Women need to provide the name of a gynecologist or qualified healthcare professional willing to provide appropriate follow-up care if indicated
Exclusion Criteria:
• Female: Less than 50 years old or older than 75 years at the time of enrollment.
• Psychiatric or psychological or other conditions which prevent a fully informed consent.
• Prior removal of both ovaries.
• Active non-ovarian malignancy.
• Women who have a history of non-ovarian malignancy will be eligible if they have no persistent or recurrent disease and have not received treatment for \>12 months. If they are on SERMS (i.e. tamoxifen or aromatase inhibitors) they will not be excluded. Women maybe undergoing or have had treatment \<12 months prior to study entry for basal cell carcinoma only.
• High risk for ovarian cancer due to familial predisposition as defined by the following: a. Known mutation in BRCA1 of BRCA2. b. Two 1st or 2nd degree relatives of same lineage who have: two ovarian cancers; one ovarian cancer \& one pre-menopausal breast cancer; two pre-menopausal breast cancers; one pre-menopausal \& one post-menopausal breast cancer. (These conditions can also be met using the patient and one 1st or 2nd degree female relative.) c. Ashkenazi Jewish descent with one 1st degree or two 2nd degree relatives with pre-menopausal breast or ovarian cancer or participant has had pre-menopausal breast cancer. d. 1st or 2nd degree male relative with breast cancer diagnosed at any age. (First degree relative defined as children, siblings and parents. Second degree relative defined as half-siblings, aunts, uncles, nieces, nephews, grandparents, and grandchildren.)
• Hereditary Nonpolyposis Colorectal Cancer (HNPCC)/Lynch Syndrome: known genetic mutation, presumed HNPCC carrier, Amsterdam criteria.
BEHAVIORAL: Questionnaire
Ovarian Cancer
Ovarian Cancer, CA 125 Algorithm, Cancer Detection, Questionnaire, Survey
UT Southwestern; Parkland Health & Hospital System