Oleclumab (MEDI9447) Epidermal Growth Factor Receptor Mutant (EGFRm) Non-small Cell Lung Cancer (NSCLC) Novel Combination Study

Inclusion Criteria

• Age ≥ 18
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Weight ≥ 35 kg
• Diagnosed with histologically or cytologically confirmed locally advanced/metastatic NSCLC with EGFRm
• For Arm A (Oleclumab + Osimertinib arms): must have received 1 prior line of therapy with an EGFR tyrosine kinase inhibitor (TKI) and confirmed T790M negative
• For Arm B (Oleclumab + AZD4635 arms): must have received at least 2 but not more than 4 prior lines of therapy.

Exclusion Criteria

• Receipt of an EGFR TKI within 14 days of the first dose of study treatment
• Receipt of any conventional or investigational anticancer therapy not otherwise specified within 21 days of the planned first dose
• Prior receipt of any investigational immunotherapy. Participants may have received agents that have local health authority approval for the disease indication
• Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed.
• Participants with a history of venous thrombosis within the past 3 months
• Participants with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 6 months
• Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment
• Other invasive malignancy within 2 years
• Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose Additional Exclusion Criteria for Arm A
• Concurrent treatment (or inability to stop therapy) with medications or herbal supplements known to be potent inducers of cytochrome P (CYP) 3A4
• Participants has a history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD
• Participants requires continuous supplemental oxygen for any reason Additional Exclusion Criteria for Arm B
• Herbal preparations/medications are not allowed throughout the study
• History of seizures excluding those that occurred due to previously untreated CNS metastasis