A Study of Cemiplimab Plus Chemotherapy Versus Cemiplimab Plus Chemotherapy Plus Other Cancer Treatments for Adult Patients With Operable Non-Small Cell Lung Cancer (NSCLC)

For people ages 18 years and up

Neoadjuvant Resectable NSCLC General Key Inclusion Criteria:

1. Histologically confirmed stage II through IIIB (N2) NSCLC, that is considered resectable with curative intent, as described in the protocol
2. Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1
3. Available formalin-fixed paraffin-embedded (FFPE) tumor sample blocks for submission, as described in the protocol
4. Eastern Cooperative Oncology Group Performance Status scale (ECOG PS) of 0 to 1
5. Adequate organ and bone marrow function, as described in the protocol

Arm Specific Inclusion Criteria:

Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2:

1. Non-squamous or squamous histology NSCLC with stage IIIB or stage IIIC disease who are not candidates for surgical resection or definitive chemoradiation per investigator assessment or stage IV (metastatic disease), who received no prior systemic treatment for recurrent or metastatic NSCLC
2. Availability of an archival or on-trial FFPE tumor tissue sample
3. ECOG performance status of 0 or 1
4. Per investigator judgment, life expectancy of at least 3 months

Neoadjuvant Resectable NSCLC General Key Exclusion Criteria:

1. Any systemic anti-cancer therapy or radiotherapy for the current tumor, as described in the protocol
2. Presence of actionable oncogenic alterations in the tumor for which an approved targeted therapy is available or for which perioperative chemoimmunotherapy is not considered an appropriate standard of care treatment, as described in the protocol
3. Presence of grade≥ 2 peripheral neuropathy
4. Another malignancy that is progressing or requires active treatment, as described in the protocol

Arm Specific Exclusion Criteria:

Neoadjuvant Resectable NSCLC - Arm 1:

1. Grade ≥3 hypercalcemia, as defined in the protocol
2. Any central nervous system (CNS) pathology that could increase the risk of immune effector cell-associated neurotoxicity syndrome (ICANS), as described in the protocol
3. Has marked baseline prolongation of the time from the start of the Q wave to the end of the T wave in electrocardiogram (QT)/corrected QT interval (QTc) interval or risk factors for prolonged QTc, as described in the protocol

Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2:

1. Untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression, as described in the protocol
2. Presence of actionable oncogenic alterations in the tumor for which a chemotherapy plus programmed cell death protein 1 (PD1) inhibitor backbone is not the appropriate initial therapy as standard of care
3. Known allergy or hypersensitivity to any components of trial interventions
4. Any condition requiring ongoing/continuous corticosteroid therapy, as described in the protocol

Neoadjuvant Resectable NSCLC - Arm 2:

1. History of encephalitis, meningitis, organic brain disease, or uncontrolled seizures within 1 year prior to the first dose of trial interventions.

Note: Other protocol-defined Inclusion/Exclusion criteria apply.