Javelin Parp Medley: Avelumab Plus Talazoparib In Locally Advanced Or Metastatic Solid Tumors

Inclusion Criteria:

   - Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid
   tumors that are not amenable for treatment with curative intent in adult patients
   with: NSCLC, TNBC, HR+ breast cancer, recurrent platinum sensitive ovarian cancer, UC,
   CRPC, and other advanced solid tumors with a BRCA or ATM gene defect

   - Mandatory primary or metastatic tumor biopsy. If archival tumor tissue is available
   from a biopsy/surgery the tumor tissue may be submitted without repeating a tumor
   biopsy during the screening period.

   - Minimum age in Japan is 20 years.

   - ECOG performance status 0 or 1.

   - Resolved acute effects of prior therapy

   - Adequate bone marrow, renal, and liver function.

   - Negative serum pregnancy test at screening.

   - Pregnant, breastfeeding females or female patients able to have children must agree to
   use highly effective method of contraception throughout the study and for at least 30
   days after the last dose of avelumab and for at least 7 months after the last dose of
   talazoparib; fertile male patients must use a condom during treatment and for at least
   4 months after the last dose of talazoparib.

   - Signed and dated informed consent.

Exclusion Criteria:

   - Prior treatment with a PARP inhibitor.

   - Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2,
   anti-CD137, OX 40, GITR, LAG 3, IDO, TDO,TIM 3, CTLA-4 antibody, or any other antibody
   or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
   Prior treatment with Sipuleucel-T for patients with mCRPC is allowed. For cohort A2
   NSCLC patients prior treatment with anti-PD-1/L1 is allowed

   - Prior anti-cancer therapy within 2 weeks prior to study enrollment. Prior radiation
   therapy within 2 weeks prior to enrollment. Prior palliative radiotherapy to
   metastatic lesion(s) is permitted, provided it has been completed 2 days prior to
   study enrollment and no clinically significant toxicities are expected (eg, mucositis,
   esophagitis).

   - Major surgery within 4 weeks prior to study enrollment.

   - Current use of immunosuppressive medication at the time of study enrollment.

   - Known prior or suspected hypersensitivity to investigational products.

   - 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.

   - Vaccination within 4 weeks of study enrollment and while on trial is prohibited except
   for administration of inactivated vaccines.

   - Diagnosis of Myelodysplastic Syndrome.

   - Patients with known brain metastases requiring steroids.

   - Participation in other studies involving investigational drug(s) within 4 weeks prior
   to study participation and/or during study participation.

   - Persisting toxicity related to prior therapy >Grade 1

   - Known HIV or AIDs-related illness.

   - Positive HBV or HCV test indicating acute or chronic infection.

   - Active infection requiring systemic therapy.

   - Clinically significant cardiovascular disease: cerebral vascular accident/stroke or
   myocardial infarction within 6 months prior to study entry; unstable angina,
   congestive heart failure or a serious cardiac arrhythmia requiring medication.

   - Current or anticipated use within 7 days prior to first dose of study drug, or
   anticipated use during the study of a strong P-gp inhibitor.

   - Other acute or chronic medical or psychiatric conditions.