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Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)

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ClinicalTrials.gov Identifier: NCT03742895
Recruitment Status : Recruiting
First Posted : November 15, 2018
Last Update Posted : October 17, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This study will evaluate the efficacy and safety of olaparib (MK-7339) monotherapy in participants with multiple types of advanced cancer (unresectable and/or metastatic) that: 1) have progressed or been intolerant to standard of care therapy; and 2) are positive for homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD).

Condition or disease Intervention/treatment Phase
Advanced Solid Neoplasms Drug: Olaparib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 370 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Olaparib Monotherapy in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer
Actual Study Start Date : December 12, 2018
Estimated Primary Completion Date : April 30, 2023
Estimated Study Completion Date : April 30, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Olaparib

Arm Intervention/treatment
Experimental: Olaparib
Participants with HRRm or HRD-positive advanced cancer will receive oral olaparib, 300 mg twice daily (BID).
Drug: Olaparib
Olaparib 300 mg administered BID as two, 150 mg oral tablets.
Other Names:
  • MK-7339
  • AZD2281
  • KU-0059436
  • LYNPARZA®




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to 53 months ]
    ORR is defined as the percentage of participants who achieve a confirmed complete response ([CR]; disappearance of all target lesions) or partial response ([PR]: ≥30% decrease in the sum of diameters of target lesions) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). For participants with prostate cancer, ORR will be based on Prostate Cancer Working Group (PCWG)-modified RECIST 1.1 as assessed by BICR.


Secondary Outcome Measures :
  1. Duration of Response (DOR) [ Time Frame: Up to 53 months ]
    DOR is defined as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death due to any cause, whichever occurs first. DOR will be assessed by BICR according to either RECIST 1.1 or PCWG-modified RECIST 1.1 for participants with prostate cancer.

  2. Overall Survival (OS) [ Time Frame: Up to 53 months ]
    OS is defined as the time from the date of the first dose to the date of death due to any cause.

  3. Progression Free Survival (PFS) [ Time Frame: Up to 53 months ]
    PFS is defined as the time from the date of the first dose to either: 1) the first documented disease progression as assessed either by BICR according to RECIST 1.1 or PCWG-modified RECIST 1.1 for participants with prostate cancer; or 2) death due to any cause, whichever occurs first.

  4. Number of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to 53 months ]
    An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing an AE will be assessed.

  5. Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE) [ Time Frame: Up to 52 months ]
    The number of participants discontinuing study treatment due to an AE will be assessed.

  6. Time to Earliest Progression by Cancer Antigen-125 (CA-125) [ Time Frame: Up to 53 months ]
    For participants with BRCA1/2 non-mutated ovarian cancer only, the time to earliest progression by CA-125 will be assessed. Progression by CA-125 is defined as an increase in CA-125 level ≥2x upper limit normal (ULN) on 2 occasions, 1 week apart. For participants with elevated CA-125 (≥ULN) at baseline, progression by CA-125 is defined as an increase in CA-125 level ≥2x the nadir value on 2 occasions, 1 week apart.



Information from the National Library of Medicine

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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 at least 1 of the genes involved in HRR or centrally-confirmed HRD.
  • For participants receiving prior platinum (cisplatin, carboplatin, or oxaliplatin either as monotherapy or in combination) for advanced (metastatic and/or unresectable) solid tumor, have no evidence of disease progression during the platinum chemotherapy.
  • Has measurable disease per RECIST 1.1 or PCWG-modified RECIST 1.1 as assessed by the local site Investigator/radiology and confirmed by BICR.
  • Is able to provide a newly obtained core or excisional biopsy of a tumor lesion or either an archival formalin-fixed paraffin embedded (FFPE) tumor tissue block or slides.
  • Has a life expectancy of at least 3 months.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 3 days of treatment initiation.
  • Male participants must agree to use contraception during the treatment period and for at least 90 days (3 months) after the last dose of study treatment and refrain from donating sperm during this period.
  • Female participants must not be pregnant or breastfeeding. Additionally, female participants must either not be a woman of childbearing potential (WOCBP) or, if a WOCBP, agree to use contraception during the treatment period and for at least 30 days (1 month) 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 5 years. Note: 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 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. Note: Participants with previously treated brain metastases may participate if radiologically stable, clinically stable, and without requirement for steroid treatment for at least 14 days prior to the first dose of study treatment.
  • 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 infection (i.e., Hepatitis B or C).
  • Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
  • Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (poly[ADP ribose]) polymerization (PARP) inhibitor.
  • Has a known hypersensitivity to the components or excipients in olaparib.
  • 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. Packed red blood cells and platelet transfusions are acceptable if not performed within 28 days of 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): NCT03742895


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

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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
AstraZeneca
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: NCT03742895     History of Changes
Other Study ID Numbers: 7339-002
MK-7339-002 ( Other Identifier: Merck Protocol Number )
2018-003007-19 ( EudraCT Number )
LYNK-002 ( Other Identifier: Merck )
194694 ( Registry Identifier: JAPIC-CTI )
First Posted: November 15, 2018    Key Record Dates
Last Update Posted: October 17, 2019
Last Verified: October 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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Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents