A Study of Avelumab, Binimetinib and Talazoparib in Patients With Locally Advanced or Metastatic RAS-mutant 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 as follows:

  1. Metastatic pancreatic ductal adenocarcinoma; or
  2. Phase 2 only: Stage IIIb/IV NSCLC or other advanced solid tumors with documented positive KRAS or NRAS mutation as determined using a validated test performed in a CAP/CLIA-certified laboratory (or other comparable local or regional certification).
* Have had disease progression during or following at least 1 and not more than 2 prior lines of treatment for advanced or metastatic disease.
* Patients with NSCLC must have previously received treatment with an anti-PD-1 or anti-PD-L1 agent for advanced disease.
* Measurable disease as per RECIST v1.1 criteria.
* Provision of a baseline tumor sample.
* Age ≥18 years (Japanese patients must be ≥20 years old)
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
* Adequate bone marrow, renal and liver functions.
* Adequate cardiac function.
* Informed consent provided.

Exclusion Criteria:

* Prior treatment with avelumab, a PARP inhibitor or MEK inhibitor.
* Prior systemic anti-cancer therapy within 2 weeks prior to study enrollment.
* Persisting toxicity related to prior therapy.
* Current use of immunosuppressive medication.
* Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, uveitis or iritis.
* Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
* Diagnosis of myelodysplastic syndrome (MDS).
* Known symptomatic brain metastases requiring steroids.
* Known history of testing positive for HIV or hepatitis.
* Clinically significant (ie, active) cardiovascular disease.
* History of thromboembolic or cerebrovascular events.
* Current or anticipated use of a P-gp inhibitor, inducer, or inhibitor of breast cancer resistance protein (BCRP)
* Uncontrolled hypertension.
* Concurrent neuromuscular disorder that is associated with the potential of elevated creatinine kinase.
* Known history of Gilbert's syndrome.
* History or current evidence of retinal degenerative disease, retinal vein occlusion (RVO) or current risk factors for RVO.
* Other acute or chronic medical or psychiatric condition.