PRIMARY OBJECTIVES:
I. Determine the safety of pegcetacoplan (APL-2) alone and in combination with pembrolizumab, and APL-2 in combination with both bevacizumab and pembrolizumab in patients with recurrent ovarian cancer with symptomatic malignant effusion (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0).
II. Effect of therapy on of malignant effusion measured by total volume of effusion drained every 3 weeks (patient diary and/or drained volume).
SECONDARY OBJECTIVES:
I. Determine progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and overall survival (OS) per immune related response criteria (irRECIST).
II. Changes in quality of life measures during the clinical trial (European Organisation for the Research and Treatment of Cancer \[EORTC\] Quality of Life Questionnaire \[QLQ\]-Core 30 \[C30\], EORTC QLQ-Ovarian version 28 \[OV28\] and Multidimensional Fatigue Symptom Inventory-Short Form \[MFSI-SF\]).
EXPLORATORY OBJECTIVES:
I. Evaluate the immunologic and phenotypic changes in malignant effusions and blood samples in all cohorts, which can include the following:
Ia. To understand the signaling mechanisms in ascites primed neutrophils and their effects on tumor cell growth.
Ib. To understand the changes in complement activation pathways. Ic. Functional assays of neutrophil, macrophage and T cells. Id. Flow cytometry for immune cell composition. Ie. Luminex assay for circulation inflammatory cytokines/chemokines, angiogenesis markers.
II. In patients with solid tumor lesions accessible by image-guided core biopsies the effects of therapy will be determined on the immune composition of tumor microenvironment. Studies on tumor may include immune cell infiltration, ribonucleic acid (RNA)-sequencing (Seq) and T cell receptor (TCR)-Seq for immune cell activation and exhaustion markers, complement deposits, genomic and transcriptomic profile.
III. Microbiome analysis from stool, tumor tissue and malignant effusions. IV. Determine the concentration (pharmacokinetics \[PK\]/pharmacodynamics \[PD\]) of APL-2 in serum and malignant effusion.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP 2A: Patients are assigned to 1 of 2 cohorts.
COHORT 2A-1: Patients receive pegcetacoplan intravenously (IV) over 20-40 minutes on day 1 of cycle 1 and then subcutaneously (SC) twice weekly (BIW) of each cycle. Patients also receive pembrolizumab IV on day 1 of each cycle. Treatment repeats every 3 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive pembrolizumab for up to 35 21-day cycles in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy and blood sample collection throughout the study.
COHORT 2A-2: Patients receive pegcetacoplan IV over 20-40 minutes on day 1 of cycle 1 and then SC BIW of each cycle. Patients also receive pembrolizumab IV and bevacizumab IV on day 1of each cycle. Treatment repeats every 3 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive pembrolizumab for up to 35 21-day cycles in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy and blood sample collection throughout the study.
GROUP 2B: Patients are assigned to 1 of 3 cohorts.
COHORT 2B-1: Patients receive pegcetacoplan IV over 20-40 minutes on day 1 of cycle 1 and then SC BIW of each cycle. Treatment repeats every 3 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles, followed by every 42 days for up to 35 total cycles in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy and blood sample collection throughout the study.
COHORT 2B-2: Patients receive pegcetacoplan IV over 20-40 minutes on day 1 of cycle 1 and then SC BIW of each cycle. Patients also receive pembrolizumab IV and bevacizumab IV on day 1 of each cycle. Treatment repeats every 3 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive pembrolizumab for up to 35 21-day cycles in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy and blood sample collection throughout the study.
COHORT 2B-3: Patients receive bevacizumab IV on day 1 of each cycle. Treatment repeats every 3 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter.
