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Active, Not Recruiting

NCT Number: NCT03742895

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)

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).

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Advanced Solid Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 2703), Berazategui, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • For all participants:
  • Has measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or Prostate Cancer Working Group (PCWG)-modified RECIST 1.1 as assessed by the local site Investigator/radiology and confirmed by Blinded independent central review (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:
  • Is not a woman of childbearing potential (WOCBP).
  • 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 non-mutated:
  • 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 BRCA1 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.

Treatment and study plan

Olaparib

Drug

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

Other names: MK-7339, AZD2281, KU-0059436, LYNPARZA®

Primary outcomes

  1. All Cohorts: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Prostate Cancer Working Group (PCWG)-modified RECIST 1.1

    Time frame: Up to approximately 78 months

    ORR was defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by the BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria (CR: no evidence of disease [NED] on bone scan; PR: non-progressive disease, non-evaluable [NE], NED, or CR on bone scan). Per protocol, RECIST 1.1 was modified to allow ≤ 10 target lesions in total (up to 5 per organ). The percentage of participants who experienced a CR or PR as assessed by BICR is presented.

Secondary outcomes

  1. All Cohorts: Duration of Response (DOR) as Assessed by BICR According to Modified RECIST 1.1 or PCWG-Modified RECIST 1.1

    Time frame: Up to approximately 78 months

    DOR was defined as the time from first documented CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) to progressive disease (PD) or death among participants with confirmed CR or PR as assessed by BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria (CR: NED on bone scan; PR: non progressive disease, NE, NED, or CR on bone scan). Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions in total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm or the appearance of ≥1 new lesions; PD confirmation (>4 weeks after initial PD) was required for participants remaining on treatment. Per PCWG, PD was >2 new bone lesions (not tumor flare) persisting >6 weeks. DOR as assessed by BICR is presented.

  2. All Cohorts: Overall Survival (OS)

    Time frame: Up to approximately 78 months

    OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. OS will be reported for all participants.

  3. All Cohorts: Progression Free Survival (PFS) as Assessed by BICR per Modified RECIST 1.1 or PCWG-Modified RECIST 1.1

    Time frame: Up to approximately 78 months

    PFS was defined as the time from first dose of study treatment to the first documented PD or death due to any cause whichever occurred first among participants as assessed by BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions in total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm or the appearance of ≥1 new lesion; PD confirmation (>4 weeks after initial PD) was required for participants remaining on treatment. Per PCWG, PD was >2 new bone lesions (not tumor flare) persisting >6 weeks. PFS as assessed by BICR is presented.

  4. All Cohorts: Number of Participants Experiencing an Adverse Event (AE)

    Time frame: Up to approximately 78 months

    An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) 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 an AE will be reported.

  5. All Cohorts: Number of Participants Discontinuing Study Treatment due to an AE

    Time frame: Up to approximately 78 months

    An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) 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 due to an AE will be reported.

  6. Combined Cohort 1+2: ORR as Assessed by BICR per Modified RECIST 1.1 or PCWG-Modified RECIST 1.1 in Participants who are HRRm Positive

    Time frame: Up to approximately 78 months

    ORR was defined as the percentage of participants who have a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) as assessed by the BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria (CR: NED on bone scan; PR: non-progressive disease, NE, NED, or CR on bone scan). Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions in total (up to 5 per organ). Per protocol, Cohort 1 and Cohort 2 were combined as a pre-specified secondary efficacy analysis population. Per protocol, the secondary ORR outcome measure analysis for HRRm positive participants in Cohort 1 (BRCA 1/2) and Cohort 2 [(HRRm, BRCA Non-mutated); (HRD+, HRR Non-mutated)] combined is presented.

  7. Progression-Free Survival After Next-Line Treatment in Participants with somatic BRCA1/2 mutations (sBRCAm) Breast Cancer

    Time frame: Up to approximately 78 months

    For participants with 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.

  8. Combined Cohort 1+2: ORR as Assessed by BICR per Modified RECIST 1.1 or PCWG-Modified RECIST 1.1 In Participants who are HRD Positive (HRD+)

    Time frame: Up to approximately 78 months

    ORR was defined as the percentage of participants who have a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) as assessed by the BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria (CR: NED on bone scan; PR: non-progressive disease, NE, NED, or CR on bone scan). Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions in total (up to 5 per organ). Per protocol, Cohort 1 and Cohort 2 were combined as a pre-specified secondary efficacy analysis population. Per protocol, the secondary ORR outcome measure analysis for HRD+ participants in Cohort 1 (BRCA 1/2) and Cohort 2 [(HRRm, BRCA Non-mutated); (HRD+, HRR Non-mutated)] combined is presented.

  9. Combined Cohort 1+2: ORR as Assessed by BICR per Modified RECIST 1.1 or PCWG-Modified RECIST 1.1 in All Combined Cohort 1+2 Participants Regardless of Biomarker Status

    Time frame: Up to approximately 78 months

    ORR was defined as the percentage of participants who have a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) as assessed by the BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria (CR: NED on bone scan; PR: non-progressive disease, NE, NED, or CR on bone scan). Per protocol, RECIST 1.1 was modified to allow ≤ 10 target lesions in total (up to 5 per organ). Per protocol, the secondary ORR outcome measure analysis for all participants regardless of biomarker status in Cohort 1 (BRCA 1/2) and Cohort 2 ([HRRm, BRCA Non-mutated]; [HRD+, HRR Non-mutated]) combined is presented.

  10. Combined Cohort 1+2: DOR as Assessed by BICR Per Modified RECIST 1.1 or PCWG-Modified RECIST 1.1 in Participants who are HRRm Positive

    Time frame: Up to approximately 78 months

    DOR was defined as the time from first documented CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) to PD or death among participants with confirmed CR or PR as assessed by BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria (CR: NED on bone scan; PR: non-progressive disease, NE, NED, or CR on bone scan). Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions in total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions with an absolute increase of ≥5 mm or the appearance of ≥1 new lesions; PD confirmation (>4 weeks after initial PD) was required for participants remaining on treatment. Per PCWG, PD was >2 new bone lesions (not tumor flare) persisting >6 weeks. Cohort 1 & 2 were combined as secondary efficacy population and DOR for HRRm-positive participants is presented.

  11. Combined Cohort 1+2: DOR as Assessed by BICR per Modified RECIST 1.1 or PCWG-Modified RECIST 1.1 In Participants Who Are HRD Positive (HRD+)

    Time frame: Up to approximately 78 months

    DOR was defined as the time from first documented CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) to PD or death among participants with confirmed CR or PR as assessed by BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria (CR: NED on bone scan; PR: non-progressive disease, NE, NED, or CR on bone scan). Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions in total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions with an absolute increase of ≥5 mm or the appearance of ≥1 new lesions; PD confirmation (>4 weeks after initial PD) was required for participants remaining on treatment. Per PCWG, PD was >2 new bone lesions (not tumor flare) persisting >6 weeks. Cohort 1 & 2 were combined as secondary efficacy population and DOR for HRD+ participants is presented.

  12. Combined Cohort 1+2: DOR as Assessed by BICR per modified RECIST 1.1 or PCWG-modified RECIST 1.1 in All Combined Cohort 1+2 Participants Regardless of Biomarker Status

    Time frame: Up to approximately 78 months

    DOR was defined as the time from first documented CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) to PD or death among participants with confirmed CR or PR as assessed by BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria (CR: NED on bone scan; PR: non progressive disease, NE, NED, or CR on bone scan). Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions in total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions with an absolute increase of ≥5 mm or the appearance of ≥1 new lesions; PD confirmation (>4 weeks after initial PD) was required for participants remaining on treatment. Per PCWG, PD was >2 new bone lesions (not tumor flare) persisting >6 weeks. DOR for all participants regardless of biomarker status is presented.

  13. Combined Cohort 1+2: OS in Participants who are HRRm Positive

    Time frame: Up to approximately 78 months

    OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. OS will be reported for all participants.

  14. Combined Cohort 1+2: OS in Participants who are HRD Positive (HRD+)

    Time frame: Up to approximately 78 months

    OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. OS will be reported for all participants.

  15. Combined Cohort 1+2: OS in All Combined Cohort 1+2 Participants Regardless of Biomarker Status

    Time frame: Up to approximately 78 months

    OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. OS will be reported for all participants.

  16. Combined Cohort 1+2: PFS as Assessed by BICR per Modified RECIST 1.1 or PCWG-Modified RECIST 1.1 in Participants who are HRRm Positive

    Time frame: Up to approximately 78 months

    PFS was defined as the time from first dose of study treatment to the first documented PD or death due to any cause whichever occurred first among participants as assessed by BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG modified RECIST 1.1 criteria. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions in total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm or the appearance of ≥1 new lesion; PD confirmation (>4 weeks after initial PD) was required for participants remaining on treatment. Per PCWG, PD was >2 new bone lesions (not tumor flare) persisting >6 weeks. Per protocol, the secondary PFS outcome measure analysis for HRRm positive participants in Cohort 1 (BRCA 1/2) and Cohort 2 [(HRRm, BRCA Non-mutated); (HRD+, HRR Non-mutated)] combined is presented.

  17. Combined Cohort 1+2: PFS as Assessed by BICR per Modified RECIST 1.1 or PCWG-Modified RECIST 1.1 in Participants who are HRD Positive (HRD+)

    Time frame: Up to approximately 78 months

    PFS was defined as the time from first dose of study treatment to the first documented PD or death due to any cause whichever occurred first among participants as assessed by BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions in total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm or the appearance of ≥1 new lesion; PD confirmation (>4 weeks after initial PD) was required for participants remaining on treatment. Per PCWG, PD was >2 new bone lesions (not tumor flare) persisting >6 weeks. Per protocol, the secondary PFS outcome measure analysis for HRD+ participants in Cohort 1 (BRCA 1/2) and Cohort 2 [(HRRm, BRCA Non-mutated); (HRD+, HRR Non-mutated)] combined is presented.

  18. Combined Cohort 1+2: PFS as Assessed by BICR per Modified RECIST 1.1 or PCWG-Modified RECIST 1.1 in All Combined Cohort 1+2 Participants Regardless of Biomarker Status

    Time frame: Up to approximately 78 months

    PFS was defined as the time from first dose of study treatment to the first documented PD or death due to any cause whichever occurred first among participants as assessed by BICR per modified RECIST 1.1. For participants with prostate cancer, response will be assessed based on PCWG-modified RECIST 1.1 criteria. Per protocol, RECIST 1.1 was modified to allow ≤10 target lesions in total (up to 5 per organ). Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm or the appearance of ≥1 new lesion; PD confirmation (>4 weeks after initial PD) was required for participants remaining on treatment. Per PCWG, PD was >2 new bone lesions (not tumor flare) persisting >6 weeks. Per protocol, the secondary ORR outcome measure analysis for all participants regardless of biomarker status in Cohort 1 (BRCA 1/2) and Cohort 2 ([HRRm, BRCA Non-mutated]; [HRD+, HRR Non-mutated]) combined is presented.

  19. Cohort 2: Time to Earliest Progression by Cancer Antigen-125 (CA-125)

    Time frame: Up to approximately 78 months

    Time to earliest progression by CA-125 was defined as the time from first dose to progression by CA-125. For participants with BRCA1/2 non-mutated ovarian cancer only, progression by CA-125 was defined as either CA-125 ≥2× upper limit normal (ULN) on 2 occasions 1 week apart or, for participants with elevated CA-125 (≥ULN) at baseline, ≥2× the nadir value on 2 occasions 1 week apart. Time to earliest progression by CA-125 as assessed is presented.

  20. Cohort 1 & 2: Prostate-specific Antigen (PSA) Response Rate in Participants with Prostate Cancer

    Time frame: Up to approximately 78 months

    PSA response was defined as a reduction in PSA level ≥50% from baseline measured twice at least 3 weeks apart. For participants with prostate cancer with baseline PSA measurements available, the PSA response rate as assessed is presented.

  21. Cohort 3: PFS2 as Assessed by the Investigator in Participants with sBRCAm Breast Cancer

    Time frame: Up to approximately 78 months

    PFS2 was defined as the time from the first dose of study medication to subsequent disease progression on next-line treatment or death due to any cause, whichever occurred first, as assessed by the investigator. PFS2 for participants with sBRCAm breast cancer in Cohort 3 is presented.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Collaborators

  • AstraZeneca

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2025
Study completion
2027
First posted
Nov 15, 2018
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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