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)

• ClinicalTrials.gov Identifier: NCT03742895
• Recruitment Status: Recruiting
• First Posted: November 15, 2018
• Last Update Posted: December 5, 2019
• Sponsor: Merck Sharp & Dohme Corp.
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Tracking Information

• First Submitted Date: November 14, 2018
• First Posted Date: November 15, 2018
• Last Update Posted Date: December 5, 2019
• Actual Study Start Date: December 12, 2018
• Estimated Primary Completion Date: April 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 14, 2018)

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.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03742895 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: February 8, 2019)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: November 14, 2018)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Solid Neoplasms

Intervention

Drug: Olaparib

Olaparib 300 mg administered BID as two, 150 mg oral tablets.

Other Names:

• MK-7339
• AZD2281
• KU-0059436
• LYNPARZA®

Study Arms

Experimental: Olaparib

Participants with HRRm or HRD-positive advanced cancer will receive oral olaparib, 300 mg twice daily (BID).

Intervention: Drug: Olaparib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 14, 2018): 370
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2023
• Estimated Primary Completion Date: April 30, 2023 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Mexico, Argentina, Australia, Canada, Colombia, Denmark, France, Guatemala, Ireland, Israel, Italy, Japan, Korea, Republic of, Peru, Romania, Russian Federation, Spain, Switzerland, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT03742895
• 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 )
• 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

• 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: Merck Sharp & Dohme Corp.
• Collaborators: AstraZeneca

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

• PRS Account: Merck Sharp & Dohme Corp.
• Verification Date: December 2019