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.