NCT05116189 · CITED IN SOURCE DOCUMENTS

Pembrolizumab/Placebo Plus Paclitaxel With or Without Bevacizumab for Platinum-resistant Recurrent Ovarian Cancer (MK-3475-B96/KEYNOTE-B96/ENGOT-ov65).

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-03-09

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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)

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outcome · POSTED

PFS Per RECIST 1.1 as Assessed by the Investigator in All Participants

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outcome · POSTED

PFS Per RECIST 1.1 by Blinded Independent Central Review (BICR) in Participants With PD-L1 CPS ≥1

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outcome · POSTED

PFS Per RECIST 1.1 by Blinded Independent Central Review (BICR) in All Participants

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outcome · NOT POSTED

Overall Survival (OS)

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outcome · NOT POSTED

Number of Participants Who Experience an Adverse Event (AE)

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outcome · NOT POSTED

Number of Participants Who Discontinue Study Treatment Due to an AE

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outcome · NOT POSTED

Change From Baseline in Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)

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outcome · NOT POSTED

Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ-C30

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outcome · NOT POSTED

Change From Baseline in the Abdominal and Gastrointestinal (GI) Symptoms Score (Items 31 to 36) Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale

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outcome · NOT POSTED

TTD in the Abdominal and GI Symptoms Score (Items 31 to 36) Using the EORTC QLQ-OV28 Abdominal/GI Symptom Scale

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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.
gender Based: true
healthy Volunteers: false
minimum Age: 18 Years
sex: FEMALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants receive pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) PLUS paclitaxel 80 mg/m\^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 every 3 weeks \[Q3W\]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.
intervention Names
Biological: Pembrolizumab
Drug: Paclitaxel
Drug: Bevacizumab
Drug: Docetaxel
label
Pembrolizumab + paclitaxel ± bevacizumab
type
EXPERIMENTAL
description
Participants receive placebo via IV infusion on Day 1 of each 6-week cycle for up to 18 cycles (approximately 2 years) PLUS paclitaxel 80 mg/m\^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an adverse event (AE) requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 every 3 weeks \[Q3W\]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.
intervention Names
Drug: Paclitaxel
Drug: Bevacizumab
Other: Placebo for pembrolizumab
Drug: Docetaxel
label
Placebo + paclitaxel ± bevacizumab
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Pembrolizumab + paclitaxel ± bevacizumab
description
IV infusion
name
Pembrolizumab
other Names
MK-3475,
KEYTRUDA®
type
BIOLOGICAL
arm Group Labels
Pembrolizumab + paclitaxel ± bevacizumab
Placebo + paclitaxel ± bevacizumab
description
IV infusion
name
Paclitaxel
type
DRUG
arm Group Labels
Pembrolizumab + paclitaxel ± bevacizumab
Placebo + paclitaxel ± bevacizumab
description
IV infusion
name
Bevacizumab
other Names
AVASTIN®, Zirabev
type
DRUG
arm Group Labels
Placebo + paclitaxel ± bevacizumab
description
IV infusion
name
Placebo for pembrolizumab
other Names
normal saline or dextrose
type
OTHER
arm Group Labels
Pembrolizumab + paclitaxel ± bevacizumab
Placebo + paclitaxel ± bevacizumab
description
IV infusion
name
Docetaxel
other Names
TAXOTERE®
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: TRIPLE
who Masked: PARTICIPANT
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 643
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
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)
time Frame
Up to ~38 months
description
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.
measure
PFS Per RECIST 1.1 as Assessed by the Investigator in All Participants
time Frame
Up to ~38 months

secondary Outcomes

description
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is 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. The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by blinded independent central review (BICR) in participants with PD-L1 CPS ≥1 is reported here. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data.
measure
PFS Per RECIST 1.1 by Blinded Independent Central Review (BICR) in Participants With PD-L1 CPS ≥1
time Frame
Up to ~38 months
description
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is 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 is also considered PD. The PFS per RECIST 1.1 as assessed by blinded independent central review (BICR) in all participants is reported here. PFS was calculated using the product-limit (Kaplan-Meier) method for censored data.
measure
PFS Per RECIST 1.1 by Blinded Independent Central Review (BICR) in All Participants
time Frame
Up to ~38 months
description
OS is defined as the time from the date of randomization to death due to any cause. The OS will be reported for all participants.
measure
Overall Survival (OS)
time Frame
Up to ~64 months
description
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be reported.
measure
Number of Participants Who Experience an Adverse Event (AE)
time Frame
Up to ~64 months
description
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be reported.
measure
Number of Participants Who Discontinue Study Treatment Due to an AE
time Frame
Up to ~64 months
description
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented.
measure
Change From Baseline in Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
time Frame
Baseline and up to ~64 months
description
TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in GHS (EORTC QLQ-C30 Items 29 and 30) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from Baseline in GHS score, will be presented. A longer TTD indicates a better outcome.
measure
Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ-C30
time Frame
Up to ~64 months
description
The EORTC QLQ-OV28 is an abdominal and gastrointestinal questionnaire (items 31-36). Participant responses to the question "Did you have abdominal pain ?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in abdominal and gastrointestinal symptoms (EORTC QLQ-LC28 Items 31-36) score will be presented. A lower score indicates a better outcome.
measure
Change From Baseline in the Abdominal and Gastrointestinal (GI) Symptoms Score (Items 31 to 36) Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale
time Frame
Baseline and up to ~64 months
description
TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in GHS (EORTC QLQ-C28 Items 31-36) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from Baseline in GHS score, will be presented. A longer TTD indicates a better outcome.
measure
TTD in the Abdominal and GI Symptoms Score (Items 31 to 36) Using the EORTC QLQ-OV28 Abdominal/GI Symptom Scale
time Frame
Up to ~64 months

Full study description

brief 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.

Source references

references

citation
Colombo N, Zsiros E, Parma G, Rulli E, Sebastianelli A, Bidzinski M, Gallardo C, Matanes E, Hasegawa K, Kose F, Magallanes-Maciel M, Herbertson RA, Ananda S, Kroep JR, de Melo AC, Debruyne PR, Kim JW, Sehouli J, Pierre ME, Hietanen S, Zamagni C, Lu X, Monk BJ, Coleman RL, Peng X, Yamada K, Bogusz AM, De La Motte Rouge T, Wu X; ENGOT-ov65/KEYNOTE-B96 investigators. Pembrolizumab plus weekly paclitaxel in platinum-resistant recurrent ovarian cancer (ENGOT-ov65/KEYNOTE-B96): a multicentre, randomised, double-blind, phase 3 study. Lancet. 2026 Apr 18;407(10538):1525-1537. doi: 10.1016/S0140-6736(26)00602-1. Epub 2026 Apr 10.
pmid
41974150
type
DERIVED
citation
Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.
pmid
37185961
type
DERIVED