Olaparib in combination with pembrolizumab in HRRm and HRD positive cancer

Phase 1

Conditions: HRRm and/or HRD-positive cancer
MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2019-001745-40-IT

Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 300

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. Is male or female, who is at least 18 years of age at the time of signing the informed consent.
6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 3 days of treatment initiation.
7. A male participant must agree to use contraception as detailed in the protocol during the treatment period and for at least 120 days (4 months), corresponding to time needed to eliminate any study intervention(s) and refrain from donating sperm during this period.
8. 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 180 days (6 months) after the last dose of study intervention, corresponding to time needed to eliminate any study intervention(s).
9. The participant (or legally acceptable representative if applicable) provides written 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.
10. 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

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 that required treatment with steroids or currently has pneumonitis
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. Were refractory to prior platinum therapy for advanced (metastatic and/or unresectable) solid tumor
20. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to administration of study intervention
21. Must have recovered from all AEs due to previous therapies, excluding alopecia, to =Grade 1 or baseline
22. Has a known hypersensitivity to the study treatments and/or any of their excipients
23. 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
24. 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
25. Has received previous allogenic bone-marrow transplant or double umbilical cord tran

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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