Pembrolizumab Combined With Bevacizumab With or Without Agonist Anti-CD40 CDX-1140 for the Treatment of Patients With Recurrent Ovarian Cancer
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|ClinicalTrials.gov Identifier: NCT05231122|
Recruitment Status : Not yet recruiting
First Posted : February 9, 2022
Last Update Posted : February 6, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Ovarian Clear Cell Adenocarcinoma Platinum-Sensitive Ovarian Carcinoma Recurrent Endometrial Serous Adenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Fallopian Tube Endometrioid Adenocarcinoma Recurrent Fallopian Tube Serous Adenocarcinoma Recurrent Ovarian Carcinoma Recurrent Ovarian Clear Cell Adenocarcinoma Recurrent Ovarian Endometrioid Adenocarcinoma Recurrent Ovarian Serous Adenocarcinoma Recurrent Platinum-Resistant Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Recurrent Primary Peritoneal Clear Cell Adenocarcinoma Recurrent Primary Peritoneal Endometrioid Adenocarcinoma Recurrent Primary Peritoneal Serous Adenocarcinoma||Biological: Anti-CD40 Agonist Monoclonal Antibody CDX-1140 Biological: Bevacizumab Biological: Pembrolizumab Other: Quality-of-Life Assessment Other: Questionnaire Administration||Phase 2|
I. Determine the safety of anti-CD40 agonist monoclonal antibody CDX-1140 (CDX-1140) combined with pembrolizumab and bevacizumab in patients with recurrent ovarian cancer (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0).
II. Determine the objective response rate (ORR) per immune related response criteria (immune-modified Response Evaluation Criteria in Solid Tumors [iRECIST]).
I. Determine progression free survival (PFS), disease control rate (DCR) and overall survival (OS).
II. Changes in quality of life measures during the clinical trial (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30], EORTC QLQ-Ovarian Cancer Module [OV28] and Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF)].
I. Pharmacokinetic (PK)/anti-drug antibody (ADA) analysis for CDX-1140. II. Evaluate the immunologic and phenotypic changes in blood samples. III. To obtain data on changes in tumor microenvironment prior to and subsequent to therapy and, to screen for potential biomarkers to predict clinical benefit.
IV. Microbiome analysis from stool, tumor tissue.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive pembrolizumab intravenously (IV) over 30 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 3 weeks until disease progression or development of unacceptable toxicity.
ARM II: Patients receive pembrolizumab IV over 30 minutes, bevacizumab IV over 30-90 minutes, and CDX-1140 IV over 90 minutes on day 1. Cycles repeat every 3 weeks until disease progression or development of unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 6 months for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Randomized Phase 2 Clinical Trial of Pembrolizumab Combined With Bevacizumab With or Without Agonist Anti-CD40 CDX-1140 in Patients With Recurrent Ovarian Cancer|
|Estimated Study Start Date :||March 15, 2023|
|Estimated Primary Completion Date :||January 15, 2026|
|Estimated Study Completion Date :||January 15, 2026|
Active Comparator: Arm I (pembrolizumab, bevacizumab)
Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 3 weeks until disease progression or development of unacceptable toxicity.
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Experimental: Arm II (pembrolizumab, bevacizumab, CDX-1140)
Patients receive pembrolizumab IV over 30 minutes, bevacizumab IV over 30-90 minutes, and CDX-1140 IV over 90 minutes on day 1. Cycles repeat every 3 weeks until disease progression or development of unacceptable toxicity.
Biological: Anti-CD40 Agonist Monoclonal Antibody CDX-1140
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
- Incidence of adverse events [ Time Frame: Up to 2 years ]Evaluated according to National Cancer Institute Common Terminology Criteria for adverse events (NCI CTCAE) version (v)5.0. Will be summarized by cohort and grade using frequencies and relative frequencies.
- Objective response rate (ORR) [ Time Frame: Up to 2 years ]Will be summarized by cohort (with or without CDX 1140) using frequencies and relative frequencies, with the ORR estimated using 90% confidence intervals obtained by Jeffrey's prior method. The final analysis will be performed on all n=80 (40 in each cohort) evaluable patients; and if the p-value is less than or equal to 0.10, then the triplet regimen will be considered superior with respect to response.
- Progression free survival (PFS) [ Time Frame: From first day of treatment until disease progression or date of death from any cause, assessed up to 2 years ]Will be summarized by cohort using standard Kaplan-Meier methods, with estimates of the median obtained with 90% confidence intervals. PFS will be compared between cohorts using a one-sided log-rank test.
- Overall survival (OS) [ Time Frame: From first day of treatment until disease progression or date of death from any cause, assessed up to 2 years ]Will be summarized by cohort using standard Kaplan-Meier methods, with estimates of the median obtained with 90% confidence intervals. OS will be compared between cohorts using a one-sided log-rank test.
- Disease control rate (DCR) [ Time Frame: Up to 2 years ]Will be summarized by cohort using frequencies and relative frequencies, with the DCR estimated by cohort using 90% confidence intervals obtained by Jeffrey's prior method. The DCR will be compared between cohorts using a one-sided Cohran-Mantel-Haenszel test.
- Quality of Life (QoL)EORTC QLQ-C30 [ Time Frame: Up to 2 years ]European Organization for Research and Treatment of Cancer (EORTC) QLQ-30 consists of 28 questions with answers that range from 1 (Not At All) to 4 (Very Much) and 2 questions that range from 1 (Very Poor) to 7 (Excellent)
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Accepts Healthy Volunteers:||No|
- 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.
- 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 and 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, if available).
- Participants 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.
- Participants 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.
- 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.
- Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment. Topical, inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if the patient is on a stable dose.
Non-absorbed intraarticular corticosteroid and replacement steroids (=< 10 mg/day prednisone or equivalent) will be permitted.
- 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.
- Other prior malignancy, except for adequately treated 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.
- Active or prior autoimmune disease except for autoimmune thyroiditis or vitiligo.
- Known active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months.
- Active or history of inflammatory bowel disease (colitis, Crohn's), diverticulitis, irritable bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions associated with diarrhea. Active or history of systemic lupus erythematosus or Wegener's granulomatosis.
- Subject has any acute infection that requires specific therapy. Acute therapy must have been completed within seven days prior to study enrollment.
- Known immunodeficiency or active human immunodeficiency virus (HIV).
- 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 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05231122
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Contact: Emese Zsiros 716-845-8337 Emese.Zsiros@roswellpark.org|
|Principal Investigator: Emese Zsiros|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Contact: Amir A. Jazaeri AAJazaeri@mdanderson.org|
|Principal Investigator: Amir A. Jazaeri|
|Principal Investigator:||Emese Zsiros||Roswell Park Cancer Institute|
|Responsible Party:||Roswell Park Cancer Institute|
|Other Study ID Numbers:||
NCI-2021-13609 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 1277721 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
|First Posted:||February 9, 2022 Key Record Dates|
|Last Update Posted:||February 6, 2023|
|Last Verified:||February 2023|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||Yes|
Carcinoma, Ovarian Epithelial
Adenocarcinoma, Clear Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Female
Endocrine System Diseases
Neoplasms, Cystic, Mucinous, and Serous
Antineoplastic Agents, Immunological
Endothelial Growth Factors