Javelin BRCA/ATM: Avelumab Plus Talazoparib in Patients With BRCA or ATM Mutant Solid Tumors

Inclusion Criteria

• BRCA1, BRCA2 and/or ATM gene defect.
• Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent
• Availability a tumor tissue sample from a diagnostic biopsy/surgery or a metastatic tumor biopsy.
• Progressive disease at study enrollment.
• Minimum age 18 years (in Japan, minimum age 20 years).
• ECOG performance status 0 or 1.
• Adequate bone marrow, renal and liver function.
• For childbearing female patients, negative serum or urine pregnancy test at screening
• Signed and dated informed consent document.

Exclusion Criteria

• Prior anti-cancer therapy or radiation therapy within 2 weeks prior to enrolment. Palliative radiotherapy to metastatic lesion(s) permitted providing that it has been completed at least 2 days prior to enrolment and no significant toxicity are expected.
• Major surgery within 4 weeks prior to study enrollment.
• Current use of immunosuppressive medication at the time of study enrollment.
• Known prior severe hypersensitivity to investigational products or any component in their formulations
• Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis.
• Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
• Prior organ transplantation including allogenic stem-cell transplantation.
• Administration of live attenuated vaccines within 4 weeks of study enrollment.
• Diagnosis of myelodysplastic syndrome.
• Known symptomatic brain metastases requiring steroids.
• Persisting toxicity related to prior therapy Grade >1.
• Known history of HIV or AIDS.
• Positive HBV or HCV test indicating acute or chronic infection.
• Active infection requiring systemic therapy.
• Clinically significant (active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months prior to study enrollment; unstable angina, congestive heart failure or a serious cardiac arrhythmia requiring medication.
• Diagnosis of any other malignancy within 2 years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast, bladder, or cervix, or low-grade prostate cancer or other early-stage low-risk cancers.
• Pregnant or breastfeeding female patients; female or male patients who are able to have children who are unable or unwilling to use contraception as outlined in the protocol.