A Study of Subcutaneous Nivolumab plus Intravenous Ipilimumab and Chemotherapy in Participants with Previously Untreated Metastatic or Recurrent NSCLC

Prior treatment

• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.
• Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) within 14 days or other immunosuppressive medications within 30 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Other illness

• Participants with active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Participants with previous malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to randomization and no additional therapy is required or anticipated to be required during the study period.
• Participants who have history of interstitial lung disease or pneumonitis that required oral or IV glucocorticoids to assist with management.

Lab values

• Any known driver mutations with available targeted therapy (including but not limited to EGFR mutations, ALK translocations, ROS-1 translocations and known BRAFV600E, that are sensitive to available targeted inhibitor therapy; participants with a known activating RET mutations and NTRK fusion gene alterations). - Positive, unknown, or indeterminate EGFR mutation status in participants of non-squamous histology are excluded.

Other

• Participants with untreated CNS metastases are excluded. - Participants are eligible if CNS metastases are asymptomatic and do not require immediate treatment or have been treated and participants have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment).
• Participants with leptomeningeal metastases (carcinomatous meningitis).

• Females and males ≥18 years of age or the legal age of consent in the jurisdiction in which the study is taking place at time of ICF signature.
• Histologically confirmed stage IV or recurrent NSCLC (as defined by the 9th edition of the IASLC Lung Cancer Staging Guidelines) of squamous or non-squamous histology.
• No prior systemic anti-cancer treatment (including EGFR, ALK, ROS-1, BRAF, RET, and NTRK inhibitors) given as primary therapy for advanced or metastatic disease.
• Prior definitive chemoradiation for locally advanced disease is permitted as long as the last administration of chemotherapy or radiotherapy (whichever was given last) occurred at least 6 months prior to randomization. Participants with locally advanced disease with recurrence after chemoradiation therapy (stage III disease, specifically refers to patients with no curative options) are eligible to enroll.
• Prior adjuvant or neoadjuvant chemotherapy for early-stage lung cancer is permitted if completed at least 6 months prior to randomization.
• ECOG Performance Status ≤ 1 at screening and confirmed prior to randomization.
• Measurable disease by CT or MRI per RECIST 1.1 criteria with radiographic tumor assessment performed within 28 days of randomization.