- Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid
tumors that are not amenable for treatment with curative intent as follows:
1. Stage IIIb/IV NSCLC with documented positive KRAS or NRAS mutation status as
determined using a validated test performed in a College of American Pathologists
(CAP)/Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (or
other comparable local or regional certification); or
2. Metastatic pancreatic ductal adenocarcinoma; or
3. Phase 2 only: 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.
- 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.