HRRm and/or HRD-positive cancer MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Interventions
Product Name: PEMBROLIZUMAB
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration uni
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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. 2. Has either centrally-confirmed known or suspected deleterious mutations in at least 1 of the specified 15 genes involved in HRR (ie, BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L) or centrally-confirmed HRD based on the Lynparza HRR-HRD assay. 3. Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology and confirmed in real time by BICR. BICR must confirm the presence of radiologically measurable disease per RECIST 1.1 for the participant to be eligible for the study. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 4. Has a life expectancy of at least 3 months. 5. Must have had CR or PR while on treatment with prior cisplatin or carboplatin, or had CR, PR, or SD while on treatment with prior oxaliplatin (either as monotherapy or in combination) for advanced (metastatic and/or unresectable) solid tumor. Participant must also not have been refractory to prior platinum-containing therapy. 6. Is male or female, who is at least 18 years of age at the time of providing the informed consent. 7. Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 3 days of treatment initiation. 8. A male participant must agree to use contraception as detailed in the protocol during the treatment period and for at least 90 days (3 months), after the last dose of olaparib, corresponding to time needed to eliminate any study intervention(s) and refrain from donating sperm during this period. 9. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: - Not a woman of childbearing potential (WOCBP) OR - A WOCBP who agrees to follow the contraceptive guidance in the Protocol during the treatment period and for at least 120 days (3 months) after the last dose of pembrolizumab and 180 days (6 months) after the last dose of olaparib, corresponding to time needed to eliminate any study intervention(s). 10. The participant (or legally acceptable representative if applicable) provides documented informed consent for the study. The participant may also provide consent for FBR. However, the participant may participate in the main study without participating in FBR. 11. Has adequate organ function; all screening laboratory tests should be performed within 10 days prior to the first dose of study intervention. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Has a known additional malignancy that is progressing or has required active treatment in the last 3 years 2. Has a history of non-infectious pneumonitis/interstitial lung disease that required treatment with steroids or currently has pneumonitis/interstitial lung disease 3. Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML 4. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis 5. Has an active infection requiring systemic therapy 6. Has active tuberculosis 7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing in the Protocol) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention 8. Has an active autoimmune disease that has required systemic treatment in the past 2 years 9. Has a history or current evidence of any condition (please refer to the Protocol), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s involvement for the full duration of the study, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator 10. Received colony-stimulating factors (eg, 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 intervention 11. Is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active, uncontrolled infection 12. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study 13. Has a known history of human immunodeficiency virus (HIV) infection. Testing for HIV at screening is only required if mandated by local health authority 14. Has known active hepatitis (ie, Hepatitis B or C) 15. Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption 16. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required 17. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137) 18. Has received prior therapy with olaparib or with any other PARP inhibitor 19. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to administration of study intervention 20. Must have recovered from all AEs due to previous therapies, excluding alopecia, to =Grade 1 or baseline 21. Has a known hypersensitivity to the study treatments and/or any of their excipients 22. Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks 23. Is currently receiving either strong or moderate inducers of CYP3A4 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 24. Has received previous allogenic bone-marrow transplant or double umbilical cord transplantation (dUCBT) 25. Has received a whole blood t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the 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;Secondary Objective: 1. To evaluate Duration of Response (DOR) as assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 2. To evaluate Progression-Free Survival (PFS) as assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 3. To evaluate Overall Survival (OS) 4. To evaluate the safety and tolerability of study treatment 5. To evaluate ORR, DOR and PFS as assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 and OS based on tumor biomarker status 6. To evaluate the time to earliest progression by cancer antigen-125 (CA-125) in participants with ovarian cancer 7. To evaluate the prostate-specific antigen (PSA) response rate in participants with prostate cancer ;Primary end point(s): 1. 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;Timepoint(s) of evaluation of this end point: 1. Up to ~3 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Duration of Response (DOR) as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Biomarker Subgroups 2. Progression-Free Survival (PFS) as Assessed by RECIST 1.1 or PCWG-modified RECIST 1.1 in Biomarker Subgroups 3. Overall Survival (OS) in Biomarker Subgroups 4. Number of Participants Who Experience an Adverse Event (AE) 5. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) 6. 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 7. 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 8. 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 9. Overall Survival (OS) in Additional Biomarker Subpopulations 10. Number of Participants with Cancer Antigen-125 (CA-125) Level of =2 × Upper Limit of Normal (ULN) Among Participants with Ovarian Cancer 11. 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 12. Number of Participants with a Change from Baseline in Prostate-Specific Antigen (PSA) Level of =50% Among Participants with Prostate Cancer ;Timepoint(s) of evaluation of this end point: 1. Up to ~3 years 2. Up to ~3 years 3. Up to ~3 years 4. Up to ~3 years 5. Up to ~3 years 6. Up to ~3 years 7. Up to ~3 years 8. Up to ~3 years 9. Up to ~3 years 10. Up to ~3 years 11. Up to ~3 years 12. Up to ~3 years | — |
Countries
Argentina, Australia, Canada, Colombia, France, Germany, Guatemala, Israel, Italy, Korea, Republic of, Latvia, Mexico, Peru, Poland, Puerto Rico, Romania, South Africa, Spain, Sweden, Turkey, Ukraine, United States
Outcome results
None listed