Javelin BRCA/ATM: Avelumab Plus Talazoparib in Patients With BRCA or ATM Mutant Solid Tumors
Condition: Locally Advanced or Metastatic Solid Tumors; Genes, BRCA 1
Intervention: Avelumab; Talazoparib
Intervention description: IV treatment; Oral treatment
Intervention MeSH terms: Avelumab; Talazoparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Single arm study with two cohorts enrolled in parallel.
Cohort 1 will enroll patients with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes
Cohort 2 will enroll patients with locally advanced or metastatic solid tumors with one or more defects in the ATM gene
Masking: None (Open Label)
Masking description: Open label
Enrollment: 202.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: BRCA, ATM

Summary:

      Avelumab in combination with talazoparib will be investigated in patients with locally
      advanced or metastatic solid tumors with a BRCA or ATM defect.
    

Eligibility criteria:

        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.