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Metastatic, recurrent, or unresectable solid tumor with a pathogenic, or presumed pathogenic, somatic mutation of one of the following homologous recombination deficiency (HRD) gene mutations: BRCA1, BRCA2, ATM, RAD51B, RAD51C, RAD54L, RAD51D, FANC/BRIP1, FANCI, FANCL, FANCN(PALB2), BARD1, CHEK1, CHEK2, CDK12, or PPP2R2A.
- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
- Participant must be ≥ 18 years of age
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Participant must have adequate organ function, defined as follows:
- Absolute neutrophil count ≥ 1,500/µL
- Platelets ≥ 100,000/µL
- Hemoglobin ≥ 9 g/dL
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60mL/min using the Cockcroft-Gault equation
- Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
- Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
- International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) ≤1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Female participant has a negative serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to use a highly effective method of contraception from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential. Non-childbearing potential is defined as follows (by other than medical reasons):
- ≥45 years of age and has not had menses for >1 year
- Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
- Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use an adequate barrier method throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. See Section 5.4 for a list of acceptable birth control methods. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
h. Male participant agrees to use a highly effective method of contraception (see Section 5.4 for a list of acceptable birth control methods) starting with the first dose of study treatment through 180 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
j. If an appropriate archival tumor tissue sample is not available, patient is willing to undergo a pre-treatment tumor biopsy.
Exclusion Criteria:
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Patients with the following malignancies will be excluded:
- Prostate cancer
- Ovarian, breast, and pancreatic patients with known germline BRCA1 or BRCA2 mutation
- Platinum sensitive ovarian cancer (defined as recurrence > 6 months from last platinum agent), unless platinum intolerant.
