A Phase 2 Study of Olaparib in Combination With Pembrolizumab in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-Positive Advanced Cancer

Study of Olaparib (MK-7339) in Combination With Pembrolizumab (MK-3475) in the Treatment of Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-Positive Advanced Cancer (MK-7339-007/KEYLYNK-007)

Sponsors

Lead sponsor: Merck Sharp & Dohme Corp.

Source Merck Sharp & Dohme Corp.
Brief Summary

The purpose of this study is to assess the efficacy and safety of treatment with olaparib (MK-7339) in combination with pembrolizumab (MK-3475) in adults with previously treated, advanced (metastatic and/or unresectable) Homologous Recombination Repair Mutation (HRRm) and/or Homologous Recombination Deficiency (HRD)-positive solid tumors.

Overall Status Recruiting
Start Date November 18, 2019
Completion Date December 11, 2023
Primary Completion Date December 11, 2023
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Prostate Cancer Working Group (PCWG)-modified RECIST 1.1 in Biomarker Subgroups Up to ~3 years
Secondary Outcome
Measure Time Frame
Duration of Response (DOR) as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Biomarker Subgroups Up to ~3 years
Progression-Free Survival (PFS) as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Biomarker Subgroups Up to ~3 years
Overall Survival (OS) in Biomarker Subgroups Up to ~3 years
Number of Participants Who Experience an Adverse Event (AE) Up to ~3 years
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) Up to ~3 years
Objective Response Rate (ORR) Based on Tumor Biomarker Status as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Additional Biomarker Subpopulations Up to ~3 years
Duration of Response (DOR) Based on Tumor Biomarker Status as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Additional Biomarker Subpopulations Up to ~3 years
Progression-Free Survival (PFS) Based on Tumor Biomarker Status as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Additional Biomarker Subpopulations Up to ~3 years
Overall Survival (OS) in Additional Biomarker Subpopulations Up to ~3 years
Number of Participants with Cancer Antigen-125 (CA-125) Level of ≥2 × Upper Limit of Normal (ULN) Among Participants with Ovarian Cancer Up to ~3 years
Number of Participants with Cancer Antigen-125 (CA-125) Level ≥2 × Nadir (Lowest) Value Among Participants with Ovarian Cancer Who Had Elevated CA-125 Levels ≥ULN at Baseline Up to ~3 years
Number of Participants with a Change from Baseline in Prostate-Specific Antigen (PSA) Level of ≥50% Among Participants with Prostate Cancer Up to ~3 years
Enrollment 300
Condition
Intervention

Intervention type: Drug

Intervention name: Olaparib

Description: Oral tablet

Arm group label: Olaparib+Pembrolizumab

Intervention type: Biological

Intervention name: Pembrolizumab

Description: Intravenous infusion

Arm group label: Olaparib+Pembrolizumab

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 ≥1 of the specified 15 genes involved in HRR or centrally-confirmed HRD based on the Lynparza HRR-HRD assay.

- Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology and confirmed in real time by blinded independent central review (BICR). BICR must confirm the presence of radiologically measurable disease per RECIST 1.1 for the participant to be eligible for the study.

- Has a life expectancy of ≥3 months.

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 3 days of study treatment initiation.

- Male participants must agree to use contraception during the treatment period and for ≥120 days (4 months) after last dose of study treatment and refrain from donating sperm during this period.

- Female participants must not be pregnant or breastfeeding, and ≥1 of the following conditions applies:

- Is not a woman of childbearing potential (WOCBP) OR

- Is a WOCBP who agrees to use contraception during the treatment period and for ≥180 days (6 months) 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 3 years. 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 a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis.

- 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.

- Has an active infection requiring systemic therapy.

- Has active tuberculosis (Bacillus tuberculosis [TB]).

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing >10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.

- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).

- 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 B or hepatitis C.

- Is unable to swallow orally administered medication or has a gastrointestinal (GI) disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction, malabsorption).

- Has received prior therapy with an anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), or anti-programmed death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40 [Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]).

- Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (poly[ADP ribose]) polymerization (PARP) inhibitor.

- Was refractory to prior platinum therapy (cisplatin, carboplatin, or oxaliplatin either as monotherapy or in combination) for advanced (metastatic and/or unresectable) solid tumor.

- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to administration of study treatment.

- Must have recovered from all adverse events (AEs) due to previous therapies, excluding alopecia, to ≤Grade 1 or Baseline.

- Has a known hypersensitivity to the study treatments and/or any of their excipients.

- Is currently receiving either strong inhibitors of cytochrome P450 (CYP)3A4 (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate inhibitors of CYP3A4 (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks.

- Is currently receiving either strong inducers of CYP3A4 (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate inducers of CYP3A4 (e.g. bosentan, efavirenz, modafinil) that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.

- 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.

- Has received prior radiotherapy within 2 weeks of start of study treatment.

- Is currently enrolled in and receiving study therapy, was enrolled in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks (28 days) of the first dose of study treatment.

- Has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fredericia [QTcF] prolongation >500 msec, electrolyte disturbances), or participant has congenital long QT syndrome.

- Has either had major surgery within 2 weeks of starting study treatment or has not recovered from any effects of any major surgery.

- Has received a live vaccine within 30 days prior to the first dose of study treatment.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Medical Director Study Director Merck Sharp & Dohme Corp.
Overall Contact

Last name: Toll Free Number

Phone: 1-888-577-8839

Email: [email protected]

Location
facility status contact
San Francisco Oncology Associates ( Site 0085) | San Francisco, California, 94115, United States Recruiting Study Coordinator 415-600-1544
University of Florida ( Site 0078) | Gainesville, Florida, 32608, United States Recruiting Study Coordinator 352-294-5152
Winship Cancer Institute of Emory University ( Site 0057) | Atlanta, Georgia, 30322, United States Recruiting Study Coordinator 404-778-4383
Northwest Georgia Oncology Centers PC ( Site 0047) | Marietta, Georgia, 30060, United States Recruiting Study Coordinator 770-333-2161
Norton Cancer Institute - St. Matthews ( Site 0024) | Louisville, Kentucky, 40207, United States Recruiting Study Coordinator 502-899-3366
New York Cancer and Blood Specialists ( Site 0080) | Port Jefferson Station, New York, 11776, United States Recruiting Study Coordinator 631-675-5075
University Hospitals Cleveland Medical Center ( Site 0016) | Cleveland, Ohio, 44106, United States Recruiting Study Coordinator 216-844-1706
University of Texas-MD Anderson Cancer Center ( Site 0087) | Houston, Texas, 77030, United States Recruiting Study Coordinator 713-563-1784
Utah Cancer Specialists ( Site 0038) | Salt Lake City, Utah, 84106, United States Recruiting Study Coordinator 801-281-6864
Inova Schar Cancer Institute ( Site 0008) | Fairfax, Virginia, 22031, United States Recruiting Study Coordinator 571-472-0633
Northwest Medical Specialties, PLLC ( Site 0007) | Tacoma, Washington, 98405, United States Recruiting Study Coordinator 253-396-5329
Hospital Britanico de Buenos Aires ( Site 2705) | Ciudad de Buenos Aires, Ciudad Autonoma De Buenos Aires, C1280AEB, Argentina Recruiting Study Coordinator +541143096897
Centro Oncologico Riojano Integral ( Site 2703) | La Rioja, F5300COE, Argentina Recruiting Study Coordinator +543804468748
Blacktown Hospital ( Site 2202) | Blacktown, New South Wales, 2148, Australia Recruiting Study Coordinator +61298818421
Tasman Oncology Research Pty Ltd ( Site 2203) | Southport, Queensland, 4215, Australia Recruiting Study Coordinator +61400142592
Monash Health-Monash Medical Centre ( Site 2205) | Clayton, Victoria, 3168, Australia Recruiting Study Coordinator +61395956666
Linear Clinical Research Ltd ( Site 2206) | Nedlands, Western Australia, 6009, Australia Recruiting Study Coordinator +61893463841
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0201) | Montreal, Quebec, H2X 1R9, Canada Recruiting Study Coordinator 514890800024672
Clinica de la Costa Ltda. ( Site 2900) | Barranquilla, Atlantico, 080020, Colombia Recruiting Study Coordinator +57353369940
Fundacion Cardiovascular de Colombia ( Site 2907) | Bucaramanga, Santander, 681002, Colombia Recruiting Study Coordinator +573215433439
CHU Jean Minjoz ( Site 0606) | Besancon, Doubs, 25030, France Recruiting Study Coordinator +33370632256
Centre Henri Becquerel ( Site 0607) | Rouen, Seine-Maritime, 76038, France Recruiting Study Coordinator +33232082230
Centro Medico Integral de Cancerologia CEMIC ( Site 3002) | Salcaja, Quetzaltenango, 09002, Guatemala Recruiting Study Coordinator +50259458053
Oncologika S.A. ( Site 3003) | Guatemala, 01010, Guatemala Recruiting Study Coordinator +50231666045
Grupo Angeles SA ( Site 3004) | Guatemala, 01015, Guatemala Recruiting Study Coordinator +50240492110
Medi-K Cayala ( Site 3005) | Guatemala, 01016, Guatemala Recruiting Study Coordinator +50255505555
Meir Medical Center ( Site 0804) | Kfar Saba, HaMerkaz, 4428164, Israel Recruiting Study Coordinator +97297472713
Rabin Medical Center ( Site 0806) | Petah Tikva, HaMerkaz, 4941492, Israel Recruiting Study Coordinator +97239378076
Rambam MC ( Site 0801) | Haifa, Heifa, 3109601, Israel Recruiting Study Coordinator +97247773003
Chaim Sheba Medical Center ( Site 0800) | Ramat Gan, Tell Abib, 5262000, Israel Recruiting Study Coordinator +97235302243
Sourasky Medical Center ( Site 0805) | Tel Aviv, Tell Abib, 6423906, Israel Recruiting Study Coordinator +97236973082
Hadassah Ein Kerem Medical Center ( Site 0802) | Jerusalem, Yerushalayim, 9101002, Israel Recruiting Study Coordinator +97226777825
ASST Grande Ospedale Metropolitano Niguarda ( Site 0700) | Milano, 20162, Italy Recruiting Study Coordinator +390264442291
Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0703) | Modena, 41124, Italy Recruiting Study Coordinator +390594224334
Istituto Nazionale Tumori Fondazione Pascale ( Site 0705) | Napoli, 80131, Italy Recruiting Study Coordinator +390815903431
Azienda Ospedaliera Universitaria Senese ( Site 0704) | Siena, 53100, Italy Recruiting Study Coordinator +390432552751
Seoul National University Bundang Hospital ( Site 2403) | Seongnam-si, Kyonggi-do, 13605, Korea, Republic of Recruiting Study Coordinator +82317877022
Seoul National University Hospital ( Site 2402) | Seoul, Seoul-teukbyeolsi [Seoul], 03080, Korea, Republic of Recruiting Study Coordinator +821090794697
Severance Hospital Yonsei University Health System ( Site 2400) | Seoul, Seoul-teukbyeolsi [Seoul], 03722, Korea, Republic of Recruiting Study Coordinator +82222288132
Samsung Medical Center ( Site 2401) | Seoul, Seoul-teukbyeolsi [Seoul], 06351, Korea, Republic of Recruiting Study Coordinator +82234103438
Daugavpils Regional Hospital ( Site 2104) | Daugavpils, 5417, Latvia Recruiting Study Coordinator +37126896160
Liepaja Regional Hospital ( Site 2101) | Liepaja, 3414, Latvia Recruiting Study Coordinator +37126351999
P. Stradina Clinical University Hospital ( Site 2102) | Riga, 1002, Latvia Recruiting Study Coordinator +37129474117
Riga East Clinical University Hospital ( Site 2103) | Riga, 1079, Latvia Recruiting Study Coordinator +37126594570
Oncosalud ( Site 3200) | Lima, 15036, Peru Recruiting Study Coordinator +51959617508
Instituto Nacional de Enfermedades Neoplasicas ( Site 3201) | Lima, 15038, Peru Recruiting Study Coordinator +5112016500
Clinica San Gabriel ( Site 3202) | Lima, 15088, Peru Recruiting Study Coordinator +51945334003
Hospital Nacional Cayetano Heredia ( Site 3203) | Lima, 15102, Peru Recruiting Study Coordinator +51953838268
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 1800) | Warszawa, Mazowieckie, 02-781, Poland Recruiting Study Coordinator +48225463382
Uniwersyteckie Centrum Kliniczne ( Site 1809) | Gdansk, Pomorskie, 80-214, Poland Recruiting Study Coordinator +48585844565
Hematology and Oncology Institute ( Site 0504) | Manati, 00674, Puerto Rico Recruiting Study Coordinator 7878847202
Ad-Vance Medical Research LLC ( Site 0505) | Ponce, 00717, Puerto Rico Recruiting Study Coordinator 7876516697
Pan American Center for Oncology Trials LLC ( Site 0501) | Rio Piedras, 00935, Puerto Rico Recruiting Study Coordinator 7873629625
Fundacion de Investigacion de Diego ( Site 0500) | San Juan, 00927, Puerto Rico Recruiting Study Coordinator 7877520003545
Cancercare Rondebosch Oncology ( Site 1901) | Cape Town, Western Cape, 7700, South Africa Recruiting Study Coordinator +27216852578
Hospital Clinic i Provincial ( Site 1302) | Barcelona, Barcelona [Barcelona], 08036, Spain Recruiting Study Coordinator +34932279214
Hospital Quiron de Madrid ( Site 1301) | Pozuelo de Alarcon, Madrid, 28223, Spain Recruiting Study Coordinator +34902151016
Hospital General Universitario Gregorio Maranon ( Site 1300) | Madrid, 28007, Spain Recruiting Study Coordinator +34914269519
Skaenes Universitetssjukhus Lund ( Site 2001) | Lund, Skane Lan [se-12], 221 85, Sweden Recruiting Study Coordinator +4646177520.
Karolinska Universitetssjukhuset Solna ( Site 2000) | Solna, Stockholms Lan [se-01], 171 76, Sweden Recruiting Study Coordinator +46700856706
Akademiska Sjukhuset ( Site 2002) | Uppsala, Uppsala Lan [se-03], 751 85, Sweden Recruiting Study Coordinator +46186115275
Baskent University Adana Training Hospital ( Site 1509) | Adana, 01250, Turkey Recruiting Study Coordinator +905353067506
Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1502) | Ankara, 06100, Turkey Recruiting Study Coordinator +905334318506
Gazi Universitesi Tip Fakultesi ( Site 1507) | Ankara, 06500, Turkey Recruiting Study Coordinator 00905055873568
Ankara Sehir Hastanesi ( Site 1508) | Ankara, 06800, Turkey Recruiting Study Coordinator +905555306271
Akdeniz Universitesi Tıp Fakultesi ( Site 1503) | Antalya, 07070, Turkey Recruiting Study Coordinator +905052312377
Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1500) | Edirne, 22030, Turkey Recruiting Study Coordinator +905322480988
Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1504) | Istanbul, 34098, Turkey Recruiting Study Coordinator +905324167355
Istanbul Medeniyet Universitesi Goztepe EAH ( Site 1505) | Istanbul, 34722, Turkey Recruiting Study Coordinator +905063509061
Ege Universitesi Tıp Fakultesi Tulay Aktas Onkoloji Hastanesi ( Site 1501) | Izmir, 35040, Turkey Recruiting Study Coordinator 00905324510608
Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 1510) | Konya, 42080, Turkey Recruiting Study Coordinator +905322679838
Inonu Universitesi Medical Fakultesi ( Site 1506) | Malatya, 44280, Turkey Recruiting Study Coordinator +905385003562
Cherkasy Regional Oncology Dispensary ( Site 1702) | Cherkasy, Cherkaska Oblast, 18009, Ukraine Recruiting Study Coordinator +380963078884
City Clinical Hosp.4 of DCC ( Site 1700) | Dnipro, Dnipropetrovska Oblast, 49102, Ukraine Recruiting Study Coordinator +380675625054
MI Precarpathian Clinical Oncology Center ( Site 1706) | Ivano-Frankivsk, Ivano-Frankivska Oblast, 76018, Ukraine Recruiting Study Coordinator +380502094000
Communal non profit enterprise Regional Clinical Oncology Center ( Site 1704) | Kharkiv, Kharkivska Oblast, 61070, Ukraine Recruiting Study Coordinator +38050655616
Khmelnitskiy Regional Onkology Dispensary ( Site 1705) | Khmelnitskiy, Khmelnytska Oblast, 29009, Ukraine Recruiting Study Coordinator +380979242755
Kirovograd Regional oncology Dispensary ( Site 1716) | Kropyvnytsky, Kirovohradska Oblast, 25011, Ukraine Recruiting Study Coordinator +380660815334
Podillya Regional Center of Oncology ( Site 1708) | Vinnytsia, Vinnytska Oblast, 21029, Ukraine Recruiting Study Coordinator +380975791841
Medical center of the Limited Liability Company Yulis ( Site 1714) | Zaporizhzhia, Zaporizka Oblast, 69035, Ukraine Recruiting Study Coordinator +380952866303
Zhytomyr Regional Oncology Center ( Site 1710) | Zhytomyr, Zhytomyrska Oblast, 10002, Ukraine Recruiting Study Coordinator +380675885098
Location Countries

Argentina

Australia

Canada

Colombia

France

Guatemala

Israel

Italy

Korea, Republic of

Latvia

Peru

Poland

Puerto Rico

South Africa

Spain

Sweden

Turkey

Ukraine

United States

Verification Date

May 2020

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Number Of Arms 1
Arm Group

Arm group label: Olaparib+Pembrolizumab

Arm group type: Experimental

Description: Participants receive olaparib 300 mg via oral tablet 2 times each day PLUS pembrolizumab 200 mg via intravenous infusion on Day 1 of each 21-day cycle. Participants may receive olaparib+pembrolizumab for up to approximately 2 years.

Patient Data Yes
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov