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Study of Olaparib (MK-7339) in Combination With Pembrolizumab (MK-3475) in the Treatment of Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-Positive Advanced Cancer (MK-7339-007/KEYLYNK-007)

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ClinicalTrials.gov Identifier: NCT04123366
Recruitment Status : Recruiting
First Posted : October 10, 2019
Last Update Posted : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE October 9, 2019
First Posted Date  ICMJE October 10, 2019
Last Update Posted Date January 21, 2020
Actual Study Start Date  ICMJE November 18, 2019
Estimated Primary Completion Date November 27, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2019)
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Prostate Cancer Working Group (PCWG)-modified RECIST 1.1 in Biomarker Subgroups [ Time Frame: Up to ~3 years ]
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The ORR for all participants will be presented by biomarker subgroup.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04123366 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 9, 2019)
  • Duration of Response (DOR) as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Biomarker Subgroups [ Time Frame: Up to ~3 years ]
    For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR for all participants who experience a CR or PR will be presented by biomarker subgroup.
  • Progression-Free Survival (PFS) as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Biomarker Subgroups [ Time Frame: Up to ~3 years ]
    PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 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 is also considered PD. The PFS for all participants will be presented by biomarker subgroup.
  • Overall Survival (OS) in Biomarker Subgroups [ Time Frame: Up to ~3 years ]
    OS is the time from randomization to death due to any cause. The OS for all participants will be presented by biomarker subgroup.
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to ~3 years ]
    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 at least one AE will be presented.
  • Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to ~3 years ]
    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 will be presented.
  • Objective Response Rate (ORR) Based on Tumor Biomarker Status as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Additional Biomarker Subpopulations [ Time Frame: Up to ~3 years ]
    ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR will be presented by biomarker subpopulation.
  • Duration of Response (DOR) Based on Tumor Biomarker Status as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Additional Biomarker Subpopulations [ Time Frame: Up to ~3 years ]
    For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR for all participants who experience a CR or PR will be presented by biomarker subpopulation.
  • Progression-Free Survival (PFS) Based on Tumor Biomarker Status as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Additional Biomarker Subpopulations [ Time Frame: Up to ~3 years ]
    PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 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 is also considered PD. PFS will be presented by biomarker subpopulation.
  • Overall Survival (OS) in Additional Biomarker Subpopulations [ Time Frame: Up to ~3 years ]
    OS is the time from randomization to death due to any cause. OS will be presented by biomarker subpopulation.
  • Number of Participants with Cancer Antigen-125 (CA-125) Level of ≥2 × Upper Limit of Normal (ULN) Among Participants with Ovarian Cancer [ Time Frame: Up to ~3 years ]
    The number of participants who have ovarian cancer and have a CA-125 level ≥2 × upper limit of normal (ULN) at 2 different assessments that are measured at least 1 week apart will be presented.
  • Number of Participants with Cancer Antigen-125 (CA-125) Level ≥2 × Nadir (Lowest) Value Among Participants with Ovarian Cancer Who Had Elevated CA-125 Levels ≥ULN at Baseline [ Time Frame: Up to ~3 years ]
    The number of participants who have ovarian cancer with an elevated CA-125 level ≥ ULN at Baseline and have a CA-125 level ≥2 × the nadir (lowest) value at 2 different assessments that are measured at least 1 week apart will be presented.
  • Number of Participants with a Change from Baseline in Prostate-Specific Antigen (PSA) Level of ≥50% Among Participants with Prostate Cancer [ Time Frame: Up to ~3 years ]
    A PSA response is defined as a reduction in the PSA level of ≥50% from Baseline measured at 2 different times at least 3 weeks apart. The number of participants who have prostate cancer and have a change from Baseline in PSA level ≥50% will be presented.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Olaparib (MK-7339) in Combination With Pembrolizumab (MK-3475) in the Treatment of Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-Positive Advanced Cancer (MK-7339-007/KEYLYNK-007)
Official Title  ICMJE A Phase 2 Study of Olaparib in Combination With Pembrolizumab in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-Positive Advanced Cancer
Brief Summary The purpose of this study is to assess the efficacy and safety of treatment with olaparib (MK-7339) in combination with pembrolizumab (MK-3475) in adults with previously treated, advanced (metastatic and/or unresectable) Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-positive solid tumors.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors
Intervention  ICMJE
  • Drug: Olaparib
    Oral tablet
    Other Names:
    • MK-7339
    • LYNPARZA®
  • Biological: Pembrolizumab
    Intravenous infusion
    Other Names:
    • MK-3475
    • KEYTRUDA®
Study Arms  ICMJE Experimental: Olaparib+Pembrolizumab
Participants receive olaparib 300 mg via oral tablet 2 times each day PLUS pembrolizumab 200 mg via intravenous infusion on Day 1 of each 21-day cycle. Participants may receive olaparib+pembrolizumab for up to approximately 2 years.
Interventions:
  • Drug: Olaparib
  • Biological: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 9, 2019)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 27, 2024
Estimated Primary Completion Date November 27, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has a histologically- or cytologically-confirmed advanced (metastatic and/or unresectable) solid tumor (except breast or ovarian cancers whose tumor has a germline or somatic BRCA mutation) that is not eligible for curative treatment and for which standard of care therapy has failed. Participants must have progressed on or be intolerant to standard of care therapies that are known to provide clinical benefit. There is no limit on the number of prior treatment regimens.
  • Has either centrally-confirmed known or suspected deleterious mutations in ≥1 of the specified 15 genes involved in HRR or centrally-confirmed HRD based on the Lynparza HRR-HRD assay.
  • Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology and confirmed in real time by blinded independent central review (BICR). BICR must confirm the presence of radiologically measurable disease per RECIST 1.1 for the participant to be eligible for the study.
  • Has a life expectancy of ≥3 months.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 3 days of study treatment initiation.
  • Male participants must agree to use contraception during the treatment period and for ≥120 days (4 months) after last dose of study treatment and refrain from donating sperm during this period.
  • Female participants must not be pregnant or breastfeeding, and ≥1 of the following conditions applies:
  • Is not a woman of childbearing potential (WOCBP) OR
  • Is a WOCBP who agrees to use contraception during the treatment period and for ≥180 days (6 months) after the last dose of study treatment.
  • Has adequate organ function

Exclusion Criteria:

  • Has a known additional malignancy that is progressing or has required active treatment in the last 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal carcinoma in situ, or cervical carcinoma in situ that has undergone potentially curative therapy are not excluded.
  • Has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis.
  • Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
  • Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has an active infection requiring systemic therapy.
  • Has active tuberculosis (Bacillus tuberculosis [TB]).
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing >10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
  • Has received colony-stimulating factors (e.g. granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 28 days prior to the first dose of study treatment.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has known active hepatitis B or hepatitis C.
  • Is unable to swallow orally administered medication or has a gastrointestinal (GI) disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction, malabsorption).
  • Has received prior therapy with an anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), or anti-programmed death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40 [Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]).
  • Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (poly[ADP ribose]) polymerization (PARP) inhibitor.
  • Was refractory to prior platinum therapy (cisplatin, carboplatin, or oxaliplatin either as monotherapy or in combination) for advanced (metastatic and/or unresectable) solid tumor.
  • Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to administration of study treatment.
  • Must have recovered from all adverse events (AEs) due to previous therapies, excluding alopecia, to ≤Grade 1 or Baseline.
  • Has a known hypersensitivity to the study treatments and/or any of their excipients.
  • Is currently receiving either strong inhibitors of cytochrome P450 (CYP)3A4 (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate inhibitors of CYP3A4 (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks.
  • Is currently receiving either strong inducers of CYP3A4 (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate inducers of CYP3A4 (e.g. bosentan, efavirenz, modafinil) that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
  • Has received previous allogenic bone-marrow transplant or double umbilical cord transplantation (dUCBT).
  • Has received a whole blood transfusion in the last 120 days prior to entry to the study.
  • Has received prior radiotherapy within 2 weeks of start of study treatment.
  • Is currently enrolled in and receiving study therapy, was enrolled in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks (28 days) of the first dose of study treatment.
  • Has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fredericia [QTcF] prolongation >500 msec, electrolyte disturbances), or participant has congenital long QT syndrome.
  • Has either had major surgery within 2 weeks of starting study treatment or has not recovered from any effects of any major surgery.
  • Has received a live vaccine within 30 days prior to the first dose of study treatment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Australia,   Canada,   Israel,   Italy,   Korea, Republic of,   Poland,   Puerto Rico,   Turkey,   United States
Removed Location Countries Latvia
 
Administrative Information
NCT Number  ICMJE NCT04123366
Other Study ID Numbers  ICMJE 7339-007
2019-001745-40 ( EudraCT Number )
MK-7339-007 ( Other Identifier: Merck )
KEYLYNK-007 ( Other Identifier: Merck )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP