Clinical Trials /

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)

NCT03742895

Description:

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).

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 7339-002
  • SECONDARY ID: MK-7339-002
  • SECONDARY ID: 2018-003007-19
  • NCT ID: NCT03742895

Conditions

  • Advanced Solid Neoplasms

Interventions

DrugSynonymsArms
OlaparibMK-7339, AZD2281, KU-0059436, LYNPARZA®Olaparib

Purpose

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 ben intolerant to standard of care therapy; and 2) are positive for homologous recombination repair mutation (HRRm) or homologous recombination deficiency (HRD).

Trial Arms

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

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 53 months
Safety Issue:
Description: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

Measure:Duration of Response (DOR)
Time Frame:Up to 53 months
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Up to 53 months
Safety Issue:
Description:OS is defined as the time from the date of allocation to the date of death due to any cause.
Measure:Progression Free Survival (PFS)
Time Frame:Up to 53 months
Safety Issue:
Description: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.
Measure:Number of Participants Experiencing an Adverse Event (AE)
Time Frame:Up to 53 months
Safety Issue:
Description: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.
Measure:Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE)
Time Frame:Up to 52 months
Safety Issue:
Description:The number of participants discontinuing study treatment due to an AE will be assessed.
Measure:Time to Earliest Progression by Cancer Antigen-125 (CA-125)
Time Frame:Up to 53 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

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