Active, not recruiting
Phase 3
Pembrolizumab/Placebo Plus Paclitaxel With or Without Bevacizumab for Platinum-resistant Recurrent Ovarian Cancer (MK-3475-B96/KEYNOTE-B96/ENGOT-ov65).
Condition(s) studied
Ovarian CancerCarcinoma, Ovarian EpithelialFallopian Tube Neoplasms
Investigational drug(s) / intervention(s)
PembrolizumabPaclitaxelBevacizumabPlacebo for pembrolizumabDocetaxel
Pembrolizumab: IV infusion
Paclitaxel: IV infusion
Bevacizumab: IV infusion
Placebo for pembrolizumab: IV infusion
Docetaxel: IV infusion
Study summary
The primary objective is to compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the investigator. The hypotheses are that pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 as assessed by the investigator for participants with programmed cell death ligand 1 (PD-L1) positive tumors (Combined Positive Score \[CPS\] ≥1) and that pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 as assessed by the investigator for all participants.
Eligibility
Inclusion Criteria:
* Has histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
* Has received 1 or 2 prior lines of systemic therapy for ovarian cancer (OC), including at least 1 prior platinum-based therapy. Participants may have received a prior poly (ADP-ribose) polymerase inhibitor (PARPi), anti-programmed cell death 1 protein (PD-1)/anti-programmed cell death ligand 1 (PD-L1) therapy, bevacizumab, or hormonal therapy; these will not be considered a separate line of therapy. Any chemotherapy regimen change due to toxicity in the absence of disease progression will be considered part of the same line of therapy.
* Has provided documented informed consent for the study.
* Has radiographic evidence of disease progression within 6 months (180 days) after the last dose of platinum-based chemotherapy for OC (i.e., platinum-resistant disease).
* Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 3 days before randomization.
* For a female participant, she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and uses a contraceptive method that is highly effective (with a failure rate of \<1% per year).
* Has radiographically evaluable disease, either measurable or nonmeasurable per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, as assessed by the local site investigator.
* Archival tumor tissue sample or newly obtained core or incisional/excisional biopsy of a tumor lesion not previously irradiated has been provided.
* Have adequate organ function.
Exclusion Criteria:
* Has nonepithelial cancers, borderline tumors, mucinous, seromucinous that is predominantly mucinous, malignant Brenner's tumor and undifferentiated carcinoma.
* Has primary platinum-refractory disease, defined as disease that has progressed per radiographic imaging while receiving or within 28 days of the last dose of first-line platinum-based therapy.
* Has prior disease progression on weekly paclitaxel alone.
* Has received \>2 prior lines of systemic therapy for OC.
* Has received prior systemic anticancer therapy including investigational agents or maintenance therapy (including bevacizumab maintenance therapy), within 4 weeks before randomization.
* Has received prior radiation therapy within 2 weeks of start of study intervention.
* Has not recovered adequately from surgery and/or any complications from the surgery.
* Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor,\[GM-CSF\] or recombinant erythropoietin) within 4 weeks before randomization.
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Has received investigational agent or has used an investigational device within 4 weeks prior to study intervention.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab, paclitaxel, or bevacizumab (if using) and/or any of their excipients.
* Has an active autoimmune disease that has required systemic treatment in the past 2 years.
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* Has an active infection requiring systemic therapy.
* Has a known history of human immunodeficiency virus (HIV) infection.
* Has a known history of Hepatitis B or known active Hepatitis C virus infection.
* Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study.
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
* Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
* Has had an allogenic tissue/solid organ transplant.
For bevacizumab treatment
* Has uncontrolled hypertension.
* Has current, clinically relevant bowel obstruction including related to underlying epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam.
* Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal bleeding within 6 months before randomization.
Primary outcome measure(s)
- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Positive Tumors (Combined Positive Score [CPS] ≥1) — Up to ~38 months
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on Investigator assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). The appearance of one or more lesions and the unequivocal progression of non-target lesions was also considered PD. Per protocol, PFS per RECIST 1.1 as assessed by the Investigator in participants with PD-L1 CPS ≥1 is reported here. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data.
- PFS Per RECIST 1.1 as Assessed by the Investigator in All Participants — Up to ~38 months
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on Investigator assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). The appearance of one or more lesions and the unequivocal progression of non-target lesions was also considered PD. PFS per RECIST 1.1 as assessed by the Investigator will be reported for all participants. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data.
Trial sites (187)
| Facility | City | Region | Status |
| HonorHealth ( Site 0041) |
Phoenix |
Arizona |
|
| Marin Cancer Care ( Site 0055) |
Greenbrae |
California |
|
| Pacific Cancer Care ( Site 0028) |
Monterey |
California |
|
| Eisenhower Medical Center ( Site 0067) |
Rancho Mirage |
California |
|
| Yale-New Haven Hospital-Smilow Cancer Hospital at Yale-New Haven ( Site 0004) |
New Haven |
Connecticut |
|
| University of Florida College of Medicine-UF Health Cancer Center/Clinical Trials Office ( Site 0054 |
Gainesville |
Florida |
|
| Sarasota Memorial Hospital ( Site 0018) |
Sarasota |
Florida |
|
| Moffitt Cancer Center ( Site 0033) |
Tampa |
Florida |
|
| Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 0005) |
Marietta |
Georgia |
|
| Advocate Medical Group-Oncology ( Site 0049) |
Park Ridge |
Illinois |
|
| Parkview Research Center at Parkview Regional Medical Center ( Site 0027) |
Fort Wayne |
Indiana |
|
| St. Vincent Hospital and Health Care Center, Inc ( Site 0032) |
Indianapolis |
Indiana |
|
| Saint Elizabeth Medical Center Edgewood-Cancer Care Center ( Site 0040) |
Edgewood |
Kentucky |
|
| WK Physicians Network / Hematology Oncology Associates ( Site 0034) |
Shreveport |
Louisiana |
|
| Mercy Medical Center - Baltimore-Medical Oncology and Hematology ( Site 0015) |
Baltimore |
Maryland |
|
| University of Massachusetts Chan Medical School-Division of Gynecologic Oncology ( Site 0003) |
Worcester |
Massachusetts |
|
| John Theurer Cancer Center at Hackensack University Medical Center ( Site 0007) |
Hackensack |
New Jersey |
|
| Roswell Park Cancer Institute ( Site 0039) |
Buffalo |
New York |
|
| Columbia University Medical Center ( Site 0010) |
New York |
New York |
|
| Novant Health Presbyterian Medical Center ( Site 0029) |
Charlotte |
North Carolina |
|
| Duke Cancer Institute ( Site 0038) |
Durham |
North Carolina |
|
| Novant Health Forsyth Medical Center ( Site 0057) |
Winston-Salem |
North Carolina |
|
| Aultman Hospital-Oncology Clinical Trials ( Site 0009) |
Canton |
Ohio |
|
| MetroHealth Medical Center-Cancer Care Center ( Site 0047) |
Cleveland |
Ohio |
|
| Providence Portland Medical Center ( Site 0048) |
Portland |
Oregon |
|
| University of Pittsburgh Medical Center Magee-Womens Hospital ( Site 0024) |
Pittsburgh |
Pennsylvania |
|
| Sanford Cancer Center ( Site 0064) |
Sioux Falls |
South Dakota |
|
| The West Clinic, PLLC dba West Cancer Center ( Site 0058) |
Germantown |
Tennessee |
|
| Texas Oncology - Dallas (Presbyterian) ( Site 0065) |
Dallas |
Texas |
|
| Texas Oncology - The Woodlands_Lee ( Site 0043) |
The Woodlands |
Texas |
|
| Inova Schar Cancer Institute ( Site 0019) |
Fairfax |
Virginia |
|
| Westmead Hospital-Department of Gynaecological Oncology ( Site 0201) |
Westmead |
New South Wales |
|
| Gallipoli Medical Research Foundation-GMRF CTU ( Site 0202) |
Brisbane |
Queensland |
|
| Epworth Freemasons ( Site 0204) |
Melbourne |
Victoria |
|
| St. John of God Subiaco Hospital ( Site 0203) |
Subiaco |
Western Australia |
|
| Institut Jules Bordet-Medicine Oncology ( Site 0302) |
Brussels |
Bruxelles-Capitale, Region de |
|
| UZ Gent-Medical oncology ( Site 0301) |
Ghent |
Oost-Vlaanderen |
|
| UZ Leuven ( Site 0303) |
Leuven |
Vlaams-Brabant |
|
| AZ Groeninge Campus Kennedylaan-Oncology ( Site 0305) |
Kortrijk |
West-Vlaanderen |
|
| Hospital Araújo Jorge ( Site 0401) |
Goiânia |
Goiás |
|
+ 147 more sites — see the full list on the official registry below.