Olaparib in combination with pembrolizumab in HRRm and HRD positive cancer

Phase 1

Conditions: The treatment of participants with HRRm and/or HRD-positive cancer
MedDRA version: 21.1Level: LLTClassification code: 10065252Term: Solid tumor Class: 10029104
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2023-503831-17-00

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 425

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., Must have had CR or PR while on the last treatment with prior cisplatin or carboplatin, or if received only oxaliplatin had CR, PR, or stable disease (SD) while on the last 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., 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 =90 days (3 months) after the last dose of olaparib 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 =120 days (3 months) after the last dose of pembrolizumab and 180 days (6 months) after the last dose of olaparib, has a highly sensitive pregnancy test within 24 hours for urine or within 72 hours for serum before the first dose of study intervention, and abstains from breastfeeding during the study intervention period and for at least 120 days after the last dose of the study intervention., 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 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., 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 a history of non-infectious pneumonitis/interstitial lung disease that required treatment with steroids or currently has pneumonitis/interstitial lung disease., 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., The presence of 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