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: May 15, 2023
• Sponsor: Merck Sharp & Dohme LLC
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: November 14, 2018
• First Posted Date: November 15, 2018
• Last Update Posted Date: May 15, 2023
• Actual Study Start Date: December 12, 2018
• Estimated Primary Completion Date: December 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2020)

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, modified to follow a maximum of 10 target lesions in total and a maximum of 5 target lesions per organ (modified 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 (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.

Current Secondary Outcome Measures (submitted: October 5, 2020)

• 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 modified 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 modified 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.
• Objective Response Rate (ORR) in Participants with HRRm or HRD Positive Cancer [ Time Frame: Up to 53 months ]
  For participants with homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD) positive cancer, the ORR will be assessed. 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, modified to follow a maximum of 10 target lesions in total and a maximum of 5 target lesions per organ (modified 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.
• 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.
• Prostate-specific Antigen (PSA) Response Rate in Participants with Prostate Cancer [ Time Frame: Up to 53 months ]
  For participants with prostate cancer, the PSA response rate will be presented. PSA response rate is defined as the percentage of participants in the analysis population with PSA reduction of ≥50% from baseline measured twice at least 3 weeks apart.
• Progression-Free Survival After Next-Line Treatment in Participants with sBRCAm Breast Cancer [ Time Frame: Up to 53 months ]
  For participants with somatic BRCA mutated (sBRCAm) breast cancer, the PFS after next-line treatment will be presented. PFS is defined as the time from the date of the first dose to either: 1) the first documented disease progression on the next-line of treatment, as assessed by BICR according to modified RECIST 1.1; or 2) death due to any cause, whichever occurs first.

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: Allocation: N/A; 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: October 5, 2020): 390
• Original Estimated Enrollment (submitted: November 14, 2018): 370
• Estimated Study Completion Date: December 1, 2025
• Estimated Primary Completion Date: December 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• For all participants:
• 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 7 days of treatment initiation.
• Male participants must agree to use contraception during the treatment period and for at least 95 days (3 months and 5 days) after the last dose of study treatment and refrain from donating sperm during this period.

• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

  1. Is not a woman of childbearing potential (WOCBP).
  2. Is a WOCBP and using a contraceptive method that is highly effective 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 180 days 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. Abstains from breastfeeding during the study intervention period and for at least 30 days after the last dose of study intervention.
• Has adequate organ function.
• For participants who have non-breast or -ovarian cancers that are breast cancer susceptibility gene 1/2 (BRCA1/2) mutated (BRCAm), or who have cancers that are BRCA1/2 non-mutated and homologous recombination repair nonmutated:
• Has a histologically- or cytologically-confirmed advanced (metastatic and/or unresectable) solid tumor (except ovarian cancer whose tumor has a germline or somatic BRCA mutation and breast cancer whose tumor has a germline 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 or ≤4 weeks of completing the platinum-containing regimen.
• For participants who have somatic BRCAm breast cancer:
• Has histologically- or cytologically-confirmed breast cancer with evidence of metastatic disease.
• Has a known or suspected deleterious mutation in breast cancer susceptibility gene (BRCA) 1 or BRCA2 and does not harbor a germline BRCA1 or BRCA2 mutation - testing can be done centrally or locally. Blood and tissue samples must be provided by all participants.
• Has received treatment with an anthracycline unless contraindicated and a taxane in either the neoadjuvant/adjuvant or metastatic setting.
• Participants with estrogen and/or progesterone receptor-positive disease must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy.

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.
• Has received any anti-neoplastic systemic chemotherapy or biological therapy, targeted therapy, or an anticancer hormonal therapy within 3 weeks prior to the first dose of study intervention.
• Has a primary cancer of unknown origin.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.

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: Argentina, Australia, Canada, Colombia, Denmark, France, Guatemala, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, 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 ); LYNK-002 ( Other Identifier: Merck ); 194694 ( Registry Identifier: JAPIC-CTI ); 2018-003007-19 ( EudraCT Number )
• 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

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: AstraZeneca

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: May 2023