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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 : December 5, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: Olaparib Biological: Pembrolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 18, 2019
Estimated Primary Completion Date : November 27, 2024
Estimated Study Completion Date : November 27, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Olaparib
Oral tablet
Other Names:
  • MK-7339
  • LYNPARZA®

Biological: Pembrolizumab
Intravenous infusion
Other Names:
  • MK-3475
  • KEYTRUDA®




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.



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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT04123366


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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United States, Utah
Utah Cancer Specialists ( Site 0038) Recruiting
Salt Lake City, Utah, United States, 84106
Contact: Study Coordinator    801-281-6864      
United States, Washington
Northwest Medical Specialties, PLLC ( Site 0007) Recruiting
Tacoma, Washington, United States, 98405
Contact: Study Coordinator    253-396-5329      
Israel
Hadassah Ein Kerem Medical Center ( Site 0802) Recruiting
Jerusalem, Israel, 9112001
Contact: Study Coordinator    +97226777825      
Rabin Medical Center ( Site 0806) Recruiting
Petah Tikva, Israel, 4941492
Contact: Study Coordinator    +97239378076      
Korea, Republic of
Seoul National University Hospital ( Site 2402) Recruiting
Seoul, Korea, Republic of, 03080
Contact: Study Coordinator    +821090794697      
Severance Hospital Yonsei University Health System ( Site 2400) Recruiting
Seoul, Korea, Republic of, 03722
Contact: Study Coordinator    +82222288132      
Puerto Rico
Ad-Vance Medical Research LLC ( Site 0505) Recruiting
Ponce, Puerto Rico, 00717
Contact: Study Coordinator    7876516697      
Pan American Center for Oncology Trials LLC ( Site 0501) Recruiting
Rio Piedras, Puerto Rico, 00935
Contact: Study Coordinator    7873629625      
Fundacion de Investigacion de Diego ( Site 0500) Recruiting
San Juan, Puerto Rico, 00927
Contact: Study Coordinator    7877520003545      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04123366     History of Changes
Other Study ID Numbers: 7339-007
2019-001745-40 ( EudraCT Number )
MK-7339-007 ( Other Identifier: Merck )
KEYLYNK-007 ( Other Identifier: Merck )
First Posted: October 10, 2019    Key Record Dates
Last Update Posted: December 5, 2019
Last Verified: December 2019
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pembrolizumab
Olaparib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action