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

Open to people ages 18-101

1. Age ≥ 18
2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
3. Weight ≥ 35 kg
4. 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.

1. Receipt of an EGFR TKI within 14 days of the first dose of study treatment
2. Receipt of any conventional or investigational anticancer therapy not otherwise specified within 21 days of the planned first dose
3. Prior receipt of any investigational immunotherapy. Participants may have received agents that have local health authority approval for the disease indication
4. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed.
5. Participants with a history of venous thrombosis within the past 3 months
6. Participants with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 6 months
7. Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment
8. Other invasive malignancy within 2 years
9. Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression
10. Current or prior use of immunosuppressive medication within 14 days prior to the first dose

Additional Exclusion Criteria for Arm A

1. Concurrent treatment (or inability to stop therapy) with medications or herbal supplements known to be potent inducers of cytochrome P (CYP) 3A4
2. 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
3. Participants requires continuous supplemental oxygen for any reason

Additional Exclusion Criteria for Arm B

1. Herbal preparations/medications are not allowed throughout the study
2. History of seizures excluding those that occurred due to previously untreated CNS metastasis