Neoplasms

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Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Ovarian Diseases

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Genital Diseases, Female

Genital Diseases

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Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

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Endometrial Neoplasms

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Ovarian Cancer

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All Drugs and Chemicals

Antineoplastic Agents

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Antibodies, Monoclonal

Bevacizumab

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Immunoglobulin G

Endothelial Growth Factors

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Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Immune Checkpoint Inhibitors

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 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.

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.

(Expansion) 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.

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.

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.

Biopsy

Biospecimen Collection

Pegcetacoplan

Questionnaire Administration

Emese Zsiros

This phase II trial studies the effect of APL-2 when given in combination with either pembrolizumab or pembrolizumab and bevacizumab compared with bevacizumab alone in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent) and a buildup of fluid and cancer cells (malignant effusion). APL-2 may limit tumor progression, decrease malignant effusion production, and improve the immune system's response against cancer cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving APL-2 together with either pembrolizumab or pembrolizumab and bevacizumab may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer and malignant effusion compared to bevacizumab alone.

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.

APL-2 and Pembrolizumab Versus APL-2, Pembrolizumab and Bevacizumab Versus Bevacizumab Alone for the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer and Malignant Effusion

Randomized Phase 2 Trial of APL-2 With Pembrolizumab vs. APL-2 With Pembrolizumab and Bevacizumab vs. Bevacizumab Alone in Patients With Recurrent Ovarian Cancer and Persistent Malignant Effusion

APL-2 measures and immune markers will be summarized by cohort and time-point using the appropriate descriptive statistics. Each measure will be model as a function of cohort, time, their two-way interaction, and a random subject effect using a linear mixed model. Comparisons between cohorts within timepoint or between timepoints within cohort will be made using tests about the appropriate contrasts of model estimates. All model assumptions will be evaluated graphically, and transformations will be applied as appropriate.

Toxicities and adverse events (as per Common Terminology Criteria for Adverse Events version 5.0) will be summarized by cohort and grade using frequencies and relative frequencies.

Will determine the effect of therapy on accumulation of effusion measured by total volume removed every 3 weeks. The change in accumulation of effusion (relative to pre-treatment) will be modeled as a function of cohort, time-point, their two-way interaction, baseline levels, and a random subject effect using a linear mixed model. The change will be compared: a) over-time within each cohort, and b) between the control cohort (cohort C) and each dosing cohort (cohorts A and B) using two-sided Bonferroni or Dunnet adjusted tests about the appropriate contrasts of model estimates. The model assumptions will be evaluated graphically, and transformations will be applied as appropriate.

Will be summarized by cohort using standard Kaplan-Meier methods. As an exploratory analysis, the two dosing cohorts (cohorts A and B) may be compared to the control cohort (cohort C) compared using one-sided log-rank tests.

Will be summarized by cohort using standard Kaplan-Meier methods, where estimates of median PFS are obtained with 90% confidence intervals. As an exploratory analysis, the two dosing cohorts (cohorts A and B) may be compared to the control cohort (cohort C) compared using one-sided log-rank tests.

Will be summarized by cohort using frequencies and relative frequencies.

Defined as the proportion of patients who have a partial or complete response to therapy. Will be estimated by cohort using 95% confidence intervals obtained by Jeffrey's prior method.

Defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease. Will be estimated by cohort using 95% confidence intervals obtained by Jeffrey's prior method.

The QoL scores will be summarized by cohort and time-point using the appropriate descriptive statistics. Each QoL score will be model as a function of cohort, time, their two-way interaction, and a random subject effect using a linear mixed model. Comparisons between cohorts within timepoint or between timepoints within cohort will be made using tests about the appropriate contrasts of model estimates. All model assumptions will be evaluated graphically, and transformations will be applied as appropriate.

National Cancer Institute (NCI)

Roswell Park Cancer Institute

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
APL-2 and Pembrolizumab Versus APL-2, Pembrolizumab and Bevacizumab Versus Bevacizumab Alone for the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer and Malignant Effusion	NCT04919629	Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Ovarian Carcino... Ovarian Clear C... Ovarian Endomet... Ovarian Serous ... Primary Periton... Primary Periton... Primary Periton... Primary Periton... Recurrent Fallo... Recurrent Ovari... Recurrent Prima...	Bevacizumab Biopsy Biospecimen Col... Pegcetacoplan Pembrolizumab Questionnaire A...	18 Years -	Roswell Park Cancer Institute
APL-2 and Pembrolizumab Versus APL-2, Pembrolizumab and Bevacizumab Versus Bevacizumab Alone for the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer and Malignant Effusion	NCT04919629	Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Ovarian Carcino... Ovarian Clear C... Ovarian Endomet... Ovarian Serous ... Primary Periton... Primary Periton... Primary Periton... Primary Periton... Recurrent Fallo... Recurrent Ovari... Recurrent Prima...	Bevacizumab Biopsy Biospecimen Col... Pegcetacoplan Pembrolizumab Questionnaire A...	18 Years -	Roswell Park Cancer Institute

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