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    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2020-005027-37
    Sponsor's Protocol Code Number:MK3475-B96/ENGOT-ov65
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2021-12-14
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2020-005027-37
    A.3Full title of the trial
    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)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Pembrolizumab/placebo plus paclitaxel with or without bevacizumab for platinum-resistant recurrent ovarian cancer.
    A.4.1Sponsor's protocol code numberMK3475-B96/ENGOT-ov65
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
    B.5.2Functional name of contact pointGlobal Clinical Trials Operations
    B.5.3 Address:
    B.5.3.1Street AddressOne Merck Drive P.O. Box 100
    B.5.3.2Town/ cityWhitehouse Station, New Jersey
    B.5.3.3Post code08889-0100
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1732594-1882
    B.5.6E-mailkarin.yamada@merck.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name KEYTRUDA® (Pembrolizumab, MK-3475)
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code MK-3475
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPembrolizumab
    D.3.9.1CAS number 1374853-91-4
    D.3.9.2Current sponsor codeMK-3475
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Platinum-resistant Recurrent Ovarian Cancer
    E.1.1.1Medical condition in easily understood language
    Ovarian cancer which had progressed under previous platinum-based chemotherapy regimen.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10066697
    E.1.2Term Ovarian cancer recurrent
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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 RECIST 1.1 as assessed by the investigator
    E.2.2Secondary objectives of the trial
    1. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab with respect to overall survival (OS)
    2. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab with respect to PFS per RECIST 1.1 by blinded independent central review (BICR) for PD-L1+ (CPS ≥1) and all participants
    3. To evaluate safety and tolerability of pembrolizumab plus paclitaxel with or without bevacizumab
    4. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to Global Health Status/Quality of Life (GHS/QoL) score using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and abdominal/gastrointestinal (GI) symptoms using EORTC Ovarian Cancer-Specific Quality of Life Questionnaire (QLQ-OV28) for PD-L1+ (CPS ≥1) and all participants
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    A participant will be eligible for inclusion in the study if the participant meets the following criteria:
    1. Has histologically confirmed epithelial (including high-grade serous or predominantly serous, low-grade serous, any-grade endometrioid, malignant mixed Müllerian tumors [carcinosarcoma], or clear cell) ovarian, fallopian tube, or primary peritoneal carcinoma.
    2. Has received 1 or 2 prior lines of systemic therapy for OC, including at least 1 prior platinum-based therapy.
    – Participants must have received at least 4 cycles of platinum-based therapy in first line.
    – Adjuvant ± neoadjuvant therapy is considered 1 line
    – Participants may have received a prior PARPi; this will not be considered a separate line of therapy if received in maintenance
    – Participants may have received a prior anti-PD-1/anti-PD-L1 therapy or bevacizumab; 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
    3. Has radiographic evidence of disease progression within 6 months (180 days) after the last dose of platinum-based chemotherapy for OC (ie, platinum-resistant disease).
    4. Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
    5. Is female, and at least 18 years of age, at the time of signing the informed consent.
    6. Has an ECOG performance status of 0 to 1 assessed within 3 days before randomization.
    7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
    • Is not a WOCBP
    OR
    • Is a WOCBP and:
    - Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows:
    -- Pembrolizumab: 120 days
    -- Paclitaxel (or docetaxel, if applicable): 180 days
    -- Bevacizumab (if administered): 180 days
    The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
    Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
    - Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
    - Has had her medical history, menstrual history, and recent sexual activity reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy.
    8. The participant (or legally acceptable representative) has provided documented informed consent for the study. The participant may also provide consent for FBR. However, the participant may participate in the study without participating in FBR.
    9. Has radiographically evaluable disease, either measurable or nonmeasurable per RECIST 1.1, as assessed by the local site investigator/ radiology.
    10. Archival tumor tissue sample or newly obtained core or incisional/ excisional biopsy of a tumor lesion not previously irradiated has been provided. Prospective determination of PD-L1 status by a central laboratory is required for all participants.
    11. Have adequate organ function. Specimens must be collected within 7 days before randomization.
    E.4Principal exclusion criteria
    The participant must be excluded from the study if the participant meets the following criteria:
    1. Has nonepithelial cancers (germ cell tumors and sex cord-stromal tumors), borderline tumors (low malignant potential), mucinous, seromucinous that is predominantly mucinous, malignant Brenner’s tumor and undifferentiated carcinoma.
    2. Has primary platinum-refractory disease, defined as disease that has progressed per RECIST 1.1 while receiving first-line platinum-based therapy.
    3. Has prior disease progression on weekly paclitaxel alone.
    4. Has uncontrolled hypertension.
    5. Has current, clinically relevant bowel obstruction (including subocclusive disease) including related to underlying epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam.
    6. Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal bleeding within 6 months before randomization.
    7. Has received >2 prior lines of systemic therapy for OC.
    8. Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
    9. Has received prior radiation therapy within 2 weeks of start of study intervention.
    10. Has not recovered adequately from surgery and/or any complications from the surgery.
    11. Has received colony-stimulating factors (eg, G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks before randomization.
    12. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
    13. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
    14. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study medication.
    15. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
    16. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days before the first dose of study intervention.
    17. Has severe hypersensitivity (≥Grade 3) to pembrolizumab, paclitaxel, or bevacizumab (if using) and/or any of their excipients.
    18. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
    19. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
    20. Has an active infection requiring systemic therapy.
    21. Has a known history of HIV infection.
    22. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
    23. Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
    24. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
    25. Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
    26. Has had an allogenic tissue/solid organ transplant.
    E.5 End points
    E.5.1Primary end point(s)
    1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Up to ~38 months
    E.5.2Secondary end point(s)
    1. Overall Survival (OS)
    2. PFS per RECIST 1.1 by Blinded Independent Central Review (BICR)
    3. Number of Participants who Experience an Adverse Event (AE)
    4. Number of Participants who Discontinue Study Treatment due to an AE
    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)
    6. Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ-C30
    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
    8. TTD in the Abdominal and GI Symptoms Score (Items 31 to 36) Using the EORTC QLQ-OV28 Abdominal/GI Symptom Scale
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Up to ~64 months
    2. Up to ~38 months
    3. Up to ~64 months
    4. Up to ~64 months
    5. Baseline and up to ~64 months
    6. Up to ~64 months
    7. Baseline and up to ~64 months
    8. Up to ~64 months
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA77
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Chile
    Colombia
    Korea, Democratic People's Republic of
    Mexico
    Turkey
    Belgium
    Brazil
    Canada
    China
    Denmark
    Finland
    Germany
    Ireland
    Israel
    Italy
    Japan
    Netherlands
    New Zealand
    Norway
    Poland
    Russian Federation
    United Kingdom
    United States
    France
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 384
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 232
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 308
    F.4.2.2In the whole clinical trial 616
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation European Network of Gynaecological Oncological Trial groups (ENGOT) Lead Group (MaNGO)
    G.4.3.4Network Country Italy
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-02-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-01-11
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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