A trial to learn how safe newer immunotherapy drugs are and how well they work with or without other anti-cancer drugs in adults with advanced, unresectable non-small cell lung cancer

Prior treatment

• History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years prior to treatment assigment and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease.
• Active or prior documented autoimmune or inflammatory disorders requiring chronic systemic treatment.
• Any prior or current systemic or radiation therapy received for NSCLC, or prior radiation therapy for any malignancy that included any lung tissue in the prior radiation fields.
• Prior exposure to an anti-PD-1, anti-PD-L1, or anti-TIGIT therapy, or any other anticancer therapy targeting immune regulatory receptors or mechanisms.

Other illness

• Malignant pleural or pericardial effusion. Effusions must be assessed via thoracentesis or pericardiocentesis.
• History of idiopathic pulmonary fibrosis, ILD, non-infectious/radiation ILD/pneumonitis that required steroids or any active signs of these conditions that cannot be ruled out by imaging at screening. Additional exclusions include organizing pneumonia or drug-induced pneumonitis/ILD.
• History of organ transplant or allogeneic stem cell transplant.

Other

• Presence of small cell and/or neuroendocrine histology components; sarcomatoid variant; and/or other rare subtypes.
• Tumor invasion of the great vessels (aorta, superior/inferior vena cava, and/or intrapericardial vessels).

• Histologically or cytologically documented squamous or non-squamous NSCLC.
• Unresectable stage III NSCLC eligible for concurrent chemoradiation. (Stage should be determined based on IASLC v9.0 Staging Guidelines; resectability should be determined by a multidisciplinary evaluation.)
• Documented absence of sensitizing EGFR (epidermal growth factor) mutations and ALK (anaplastic lymphoma kinase) rearrangements.
• No known ROS1 or RET rearrangements detected as per local standard practice.
• Eligible for definitive, platinum-based cCRT to a total radiation dose of 60 Gy in 30 fractions using photons.
• ECOG performance status of 0 or 1.
• and 10. Known tumor PD-L1 "XXX" expression using documented local results with confirmed availablity of tumor tissue sample to confirm PD-L1 expression results.
• At least one lesion that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT (preferred) or MRI, and is suitable for accurate repeated measurements.
• Adequate organ and bone marrow function.