Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05116189
Recruitment Status : Recruiting
First Posted : November 10, 2021
Last Update Posted : August 12, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Carcinoma, Ovarian Epithelial Fallopian Tube Neoplasms Biological: Pembrolizumab Drug: Paclitaxel Drug: Bevacizumab Other: Placebo for pembrolizumab Drug: Docetaxel Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 616 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Versus Placebo in Combination With Paclitaxel With or Without Bevacizumab for the Treatment of Platinum-resistant Recurrent Ovarian Cancer (KEYNOTE-B96/ENGOT-ov65)
Actual Study Start Date : December 13, 2021
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : August 31, 2027


Arm Intervention/treatment
Experimental: Pembrolizumab + paclitaxel ± bevacizumab
Participants receive pembrolizumab 400 mg via intravenous (IV) infusion for eighteen 6-week 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 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.
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475,
  • KEYTRUDA®

Drug: Paclitaxel
IV infusion
Other Name: TAXOL®

Drug: Bevacizumab
IV infusion
Other Name: AVASTIN®, Zirabev

Drug: Docetaxel
IV infusion
Other Name: TAXOTERE®

Placebo Comparator: Placebo + paclitaxel ± bevacizumab
Participants receive placebo via IV infusion for eighteen 6-week 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 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.
Drug: Paclitaxel
IV infusion
Other Name: TAXOL®

Drug: Bevacizumab
IV infusion
Other Name: AVASTIN®, Zirabev

Other: Placebo for pembrolizumab
IV infusion
Other Name: normal saline or dextrose

Drug: Docetaxel
IV infusion
Other Name: TAXOTERE®




Primary Outcome Measures :
  1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator [ Time Frame: Up to ~42 months ]
    PFS is 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 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. Note: 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 the Investigator will be presented.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to ~68 months ]
    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.

  2. PFS per RECIST 1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to ~42 months ]
    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. Note: 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 will be presented.

  3. Number of Participants who Experience an Adverse Event (AE) [ Time Frame: Up to ~68 months ]
    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.

  4. Number of Participants who Discontinue Study Treatment due to an AE [ Time Frame: Up to ~68 months ]
    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.

  5. 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 ~68 months ]
    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.

  6. Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ-C30 [ Time Frame: Up to ~68 months ]
    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.

  7. 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 ~68 months ]
    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.

  8. 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 ~68 months ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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-PD-1/anti-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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05116189


Contacts
Layout table for location contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Show Show 133 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme LLC
Additional Information:
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT05116189    
Other Study ID Numbers: 3475-B96
MK-3475-B96 ( Other Identifier: Merck )
KEYNOTE-B96 ( Other Identifier: Merck )
ENGOT-ov65 ( Other Identifier: European Network of Gynaecological Oncological Trial groups )
jRCT2051210184 ( Registry Identifier: Japan Registry of Clinical Trials (jRCT) )
2020-005027-37 ( EudraCT Number )
First Posted: November 10, 2021    Key Record Dates
Last Update Posted: August 12, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme LLC:
Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Additional relevant MeSH terms:
Layout table for MeSH terms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases
Paclitaxel
Docetaxel
Bevacizumab
Pembrolizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances