Pembrolizumab Combined With Bevacizumab With or Without Agonist Anti-CD40 CDX-1140 for the Treatment of Patients With Recurrent Ovarian Cancer

Launched by ROSWELL PARK CANCER INSTITUTE · Jan 28, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for women with recurrent ovarian cancer, specifically looking at how well pembrolizumab and bevacizumab work together, with or without an additional drug called anti-CD40 CDX-1140. These medications aim to help the body's immune system fight the cancer by shrinking tumors and potentially improving quality of life and survival. The trial is currently recruiting participants who are 18 years or older and have specific types of recurrent ovarian or related cancers, have had no more than three prior treatments, and are expected to live for at least six months.

Participants in this trial can expect to receive the study medications and may need to undergo some tests and procedures, such as biopsies, to monitor their response to treatment. It's important for participants to be in relatively good health, meaning they should have manageable side effects from previous treatments and meet certain medical criteria. Women who are pregnant or breastfeeding cannot participate, and those with certain health conditions may also be excluded. Overall, this trial aims to explore new ways to combat recurrent ovarian cancer and improve outcomes for patients.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • Age \>= 18 years of age.
• • Recurrent serous, endometrioid, or clear cell recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
• • Participant can be either platinum-sensitive or platinum-resistant, no more than 3 prior lines of treatment, and BRCA status must be known.
• • Anticipated lifespan greater than 6 months.
• • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• • Patient has measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present.
• • All residual toxicity related to prior anti-cancer therapies (excluding alopecia, grade 2 fatigue, vitiligo, endocrinopathies on stable replacement therapy, grade 2 neuropathy from taxanes or platinum and grade 2 hearing loss from platinum) must be resolved to grade 1 severity or less (or returned to baseline) prior to receipt of study treatment.
• • Absolute neutrophil count (ANC): \>= 1,500 /mcL.
• • Platelets: \>= 100,000 / mcL.
• • Hemoglobin: \>= 9 g/dL or 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment).
• • Creatinine clearance \>= 50 mL/min.
• • Urine protein creatinine ratio (UPCR) \< 1 prior to enrollment.
• • Total bilirubin: =\< 2 X upper limit of normal (ULN) except patients with Gilbert's syndrome or liver involvement, who must have a total bilirubin =\< 3 mg/dL.
• • Aspartate aminotransferase (AST) ( serum glutamic-oxaloacetic transaminase \[SGOT\] ) and alanine aminotransferase (ALT) ( serum glutamate pyruvate transaminase \[SGPT\]): =\< 2.5 X ULN OR =\< 5 X ULN for participants with liver metastases.
• • Albumin: \> 2.5 mg/dL.
• • International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (APTT) =\< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
• • Participant must be willing to undergo core or excisional biopsy of a tumor lesion within 7 days prior to the first dose of investigational product and after 3 cycles of treatment(prior to cycle 4-day 1: mandatory only if available) and, at the end of treatment (optional). Participants for whom newly obtained samples cannot be provided at baseline (e.g., inaccessible or subject safety concern), may submit an archived specimen, only upon agreement from the Prinicipal Investigator, if available).
• • A woman of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• • A woman of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication (participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year). Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
• • Participant (or legal representative) must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
• Exclusion Criteria:
• • Receipt of any antibody targeting T cell checkpoint or co-stimulation pathways within 4 weeks, use of any other monoclonal based therapies within 4 weeks, and all other immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks prior to the planned start of study treatment.
• • Chemotherapy within 21 days prior to the planned start of study treatment.
• • Any kinase inhibitors within 2 weeks prior to the first dose of study treatment.
• • Any PARP inhibitors within 2 weeks or 5 half-lives (whichever is longer) prior to first dose of study treatment.
• • Progression on prior immune checkpoint blockade therapy.
• • Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks prior to the first dose of study treatment.
• • Use of other investigational drugs within 2 weeks or 5 half-lives (whichever is longer) prior to study treatment administration.
• • 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
• • Major surgery within 4 weeks prior to the first dose of study treatment. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and patients should be recovered.
• • Known or prior malignancy requiring active treatment in the past 2 years. Exception: basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.
• • Active, untreated central nervous system metastases. Patients with brain metastases identified at screening may be rescreened after the lesion(s) have been appropriately treated; patients with treated brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study enrollment, and off corticosteroids for at least 2 weeks before administration of study drugs, and treated lesions should demonstrate no new growth on the re-screening scan.
• • History of (non-infectious) pneumonitis or has current pneumonitis, including grade 1 (asymptomatic; clinical or diagnostic observations only; intervention not indicated) pneumonitis.
• • History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
• • Prior therapy with any anti-CD40 antibody.
• • Hypersensitivity to bevacizumab, pembrolizumab, or any of its excipients.
• • Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid)
• • Known active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months.
• • Has an acute infection requiring systemic therapy
• • Known immunodeficiency or active human immunodeficiency virus (HIV)
• • Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Note: Hepatitis B and C screening tests are not required unless known history of HBV and HCV infection
• • Has received any investigational vaccines (i.e., those not licensed or approved for emergency use). Note: Any licensed COVID-19 vaccine (including for Emergency Use) is allowed in the study as long as they are mRNA vaccines, adenoviral vaccines, or inactivated vaccines. These vaccines will be treated just as any other concomitant therapy.
• • Investigational vaccines (i.e., those not licensed or approved for Emergency Use) are not allowed.
• • Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
• • Subject requires or is likely to require more than a two-week course of corticosteroids for intercurrent illness. Subject must complete the course of corticosteroids 2 weeks before screening to meet eligibility.
• • Subject has a serious, non-healing wound, ulcer, or bone fracture.
• * Subject has a clinically significant cardiovascular disease including:
• • Uncontrolled hypertension
• • Myocardial infarction or unstable angina within 6 months prior to enrollment
• • New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• • Subject has organ allografts.
• • Subject has clinical symptoms or signs of partial or complete gastrointestinal obstruction or require parenteral hydration and/or nutrition.
• • Pregnant or nursing female participants.
• • Known active alcohol or drug abuse.
• • Unwilling or unable to follow protocol requirements.
• • Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug.