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
3 other identifiers
interventional
60
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2023
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 27, 2021
CompletedFirst Posted
Study publicly available on registry
June 9, 2021
CompletedStudy Start
First participant enrolled
April 27, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2028
March 23, 2026
March 1, 2026
5 years
May 27, 2021
March 19, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events (Phase 2a)
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.
Up to 30 days after last dose
Accumulation of effusion (Phase 2b)
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.
Up to 3 years
Secondary Outcomes (6)
Overall survival
From treatment until death or last follow-up, assessed up to 3 years
Progression free survival (PFS)
From treatment initiation until disease progression, death, or last disease assessment (censored), assessed up to 3 years
Best response
Up to 3 years
Overall response rate
Up to 3 years
Disease control rate
Up to 3 years
- +1 more secondary outcomes
Other Outcomes (1)
APL-2 pharmacokinetics (PK)/pharmacodynamics (PD) and immunological
Baseline, day 1 of cycles 2, 3, and 7, and at end of treatment
Study Arms (5)
Cohort 2A-1 (pegcetacoplan, pembrolizumab)
EXPERIMENTALPatients 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.
Cohort 2A-2 (pegcetacoplan, pembrolizumab, bevacizumab)
EXPERIMENTALPatients 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.
Cohort 2B-1 (pegcetacoplan, pembrolizumab)
EXPERIMENTAL(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.
Cohort 2B-2 (pegcetacoplan, pembrolizumab, bevacizumab)
EXPERIMENTALPatients 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 (bevacizumab)
EXPERIMENTALPatients 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.
Interventions
Given IV
Undergo tumor biopsy
Undergo blood sample collection
Given IV and SC
Given IV
Ancillary studies
Eligibility Criteria
You may qualify if:
- Age \>= 18 years of age on day of signing informed consent
- Recurrent epithelial ovarian/fallopian tube or primary peritoneal cancer (serous, clear cell, endometrioid, mixed or poorly differentiated or carcinosarcoma) based on imaging or synchronous primary ovarian and uterine cancer patients with any of the histology subtypes mentioned above regardless of platinum sensitivity, prior stage or number of prior treatment lines
- Symptomatic ascites or pleural effusion or both requiring \>= 1 drainage within 4-weeks of study entry or has a peritoneal/pleural drainage catheter in place to control symptoms
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Patient has not received pembrolizumab or other immune checkpoint inhibitor treatment for 9 weeks prior to enrollment
- Life expectancy of \>= 3 months
- Absolute neutrophil count (ANC): \>= 1,500/µL
- Platelets: \>= 75,000/µL
- Hemoglobin: \>= 9 g/dL or 5.6 mmol/L (within 7 days of assessment)
- Creatinine: =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance \>= 60 mL/min (Cockcroft-Gault Equation) for participant with creatinine levels \> 1.5 X institutional ULN. GFR can also be used in place of creatinine or creatinine clearance (CrCl)
- Total bilirubin: =\< 1.5 X ULN OR direct bilirubin =\< ULN for participants with total bilirubin levels \> 1.5 ULN
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]): =\< 2.5 X ULN OR =\< 5 X ULN for participants with liver metastases
- Albumin: \> 2.5 gm/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT): =\< 1.5 unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants
- 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
- +6 more criteria
You may not qualify if:
- Is currently receiving any additional cancer therapy or participating or used an investigational drug or device within 3 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment or, is taking any other medication that might affect immune function
- Has active autoimmune disease that has required systemic treatment in the past 3 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
- Has an active infection requiring systemic therapy
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
- Participant has clinically significant cardiovascular disease including:
- Uncontrolled hypertension, defined as systolic \>150 mmHg or diastolic \>90 mmHg
- Myocardial infarction or unstable angina within 6 months prior to enrollment
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- Participant has a Grade II (NYHA) or greater peripheral vascular disease
- Participant has a clinically significant peripheral artery disease (e.g. those with claudication), within 6 months prior to study enrollment
- Pregnancy or lactation
- 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
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Roswell Park Cancer Institutelead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Emese Zsiros
Roswell Park Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 27, 2021
First Posted
June 9, 2021
Study Start
April 27, 2023
Primary Completion (Estimated)
April 30, 2028
Study Completion (Estimated)
April 30, 2028
Last Updated
March 23, 2026
Record last verified: 2026-03