Active, not recruiting
Phase 2
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)
Condition(s) studied
Advanced Solid Neoplasms
Investigational drug(s) / intervention(s)
Olaparib: Olaparib 300 mg administered BID as two, 150 mg oral tablets.
Study 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).
Eligibility
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:
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 homologous recombination repair mutated (HRRm) but BRCA1/2 non-mutated, or homologous recombination repair non-mutated but homologous recombination deficiency (HRD) positive as centrally-confirmed by the Lynparza HRR-HRD Assay:
* 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.
* 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.
Primary outcome measure(s)
- Cohorts 1, 2, 3: 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 — 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 was assessed based on PCWG-modified RECIST 1.1 criteria (CR: soft tissue CR with no evidence of disease \[NED\] on bone scan; PR: soft tissue PR with non-progressive disease, non-evaluable \[NE\], or NED on bone scan, or soft tissue CR with non-progressive disease, or NE bone scan). Per protocol, RECIST 1.1 was modified to follow a maximum of 10 target lesions in total and a maximum of 5 target lesions per organ. The percentage of participants who experienced a CR or PR as assessed by BICR is presented.
Trial sites (130)
| Facility | City | Region | Status |
| The University of Arizona Cancer Center - North Campus ( Site 0011) |
Tucson |
Arizona |
|
| St Joseph Heritage Healthcare-Oncology ( Site 0056) |
Fullerton |
California |
|
| Cedars Sinai Medical Center ( Site 0002) |
Los Angeles |
California |
|
| UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0007) |
San Francisco |
California |
|
| Rocky Mountain Regional Veterans Affairs Medical Center ( Site 0092) |
Aurora |
Colorado |
|
| Winship Cancer Institute of Emory University ( Site 0025) |
Atlanta |
Georgia |
|
| Augusta University ( Site 0028) |
Augusta |
Georgia |
|
| Markey Cancer Center ( Site 0018) |
Lexington |
Kentucky |
|
| University of Maryland ( Site 0050) |
Baltimore |
Maryland |
|
| Weinberg Cancer Institute at Franklin Square ( Site 0054) |
Baltimore |
Maryland |
|
| University of Massachusetts ( Site 0017) |
Worcester |
Massachusetts |
|
| Henry Ford Health System ( Site 0060) |
Detroit |
Michigan |
|
| Cancer Partners of Nebraska ( Site 0051) |
Lincoln |
Nebraska |
|
| Memorial Sloan Kettering Cancer Center- Monmouth ( Site 0116) |
Middletown |
New Jersey |
|
| Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 0126) |
Harrison |
New York |
|
| VA New York Harbor Healthcare System Manhattan ( Site 0094) |
New York |
New York |
|
| Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0057) |
New York |
New York |
|
| Memorial Sloan Kettering Cancer Center ( Site 0026) |
New York |
New York |
|
| Southwestern Regional Medical Center, Inc. ( Site 0079) |
Tulsa |
Oklahoma |
|
| Eastern Regional Medical Center, Inc. ( Site 0077) |
Philadelphia |
Pennsylvania |
|
| Sanford Hematology Oncology-Sioux Falls SD ( Site 0012) |
Sioux Falls |
South Dakota |
|
| Intermountain Healthcare ( Site 0043) |
St. George |
Utah |
|
| Virginia Mason Medical Center ( Site 0052) |
Seattle |
Washington |
|
| Veterans Affairs Puget Sound Health Care System [Seattle, WA] ( Site 0093) |
Seattle |
Washington |
|
| Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 2703) |
Berazategui |
Buenos Aires |
|
| Hospital Britanico de Buenos Aires ( Site 2704) |
Ciudad de Buenos Aires |
Buenos Aires F.D. |
|
| Instituto de Investigaciones Metabolicas ( Site 2700) |
Buenos Aires |
Argentina |
|
| Hospital Aleman ( Site 2702) |
Buenos Aires |
Argentina |
|
| Kinghorn Cancer Centre ( Site 2200) |
Darlinghurst |
New South Wales |
|
| MNCCI Port Macquarie Base Hospital ( Site 2201) |
Port Macquarie |
New South Wales |
|
| Linear Clinical Research Ltd ( Site 2202) |
Nedlands |
Western Australia |
|
| Sunnybrook Research Institute ( Site 0210) |
Toronto |
Ontario |
|
| Hopital Maisonneuve-Rosemont CIUSSS de l Est de L Ile de Montreal ( Site 0203) |
Montreal |
Quebec |
|
| Jewish General Hospital ( Site 0209) |
Montreal |
Quebec |
|
| Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0 |
Québec |
Quebec |
|
| Fundacion Centro de Investigacion Clinica CIC ( Site 2812) |
Medellín |
Antioquia |
|
| Rodrigo Botero SAS ( Site 2801) |
Medellín |
Antioquia |
|
| Biomelab S A S ( Site 2800) |
Barranquilla |
Atlántico |
|
| Administradora Country SA - Clinica del Country ( Site 2802) |
Bogotá |
Bogota D.C. |
|
| Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 2807) |
Bogotá |
Bogota D.C. |
|
+ 90 more sites — see the full list on the official registry below.
More Merck Sharp & Dohme LLC trials in South Korea