PRIMARY OBJECTIVES:~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]).~SECONDARY OBJECTIVES:~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)].~EXPLORATORY OBJECTIVES:~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.
This phase II trial tests whether pembrolizumab combined with bevacizumab with or without agonist anti-CD40 CDX-1140 works to shrink tumors in patients with ovarian cancer that has come back (recurrent). Anti-CD40 CDX-1140 works by stimulating certain immune cells within the tumor and, when combined with other immunotherapy treatments, may increase antitumor antibody production. Immunotherapy with monoclonal antibodies, such as pembrolizumab and bevacizumab, may help the body's immune system, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab and bevacizumab with anti-CD40 CDX-1140 may decrease symptoms, prolonged survival, and improve quality of life in patients with ovarian cancer.