Calderasib and Pembrolizumab for Non-small Cell Lung Cancer

The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: * Has histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) * Has newly diagnosed Stage IIIB/IIIC NSCLC, not eligible for curative resection or curative chemotherapy/radiation as determined by a multidisciplinary tumor board and/or by radiation oncologist, surgeon, and medical oncologist or Stage IV (M1a, M1b, or M1c) by American Joint Committee on Cancer (AJCC) Staging Manual, Version 8 * Provides an archival tumor sample (≤5 years) or newly obtained core, incisional, or excisional biopsy or fine needle aspirate (FNA) of a tumor lesion, not previously irradiated to enable central laboratory testing of kirsten rat sarcoma (KRAS) G12C mutation status, programmed cell death ligand 1 (PD-L1) status, and biomarker research * If have had adverse events (AEs) due to previous anticancer therapies, must have recovered to \< Grade 1 or baseline * If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART) * If Hepatitis B surface antigen (HBsAg) positive, have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load * If a participant has a history of Hepatitis C virus (HCV) infection, HCV viral load is undetectable Exclusion Criteria: * Has diagnosis of small cell lung cancer. For mixed tumors, if small cell elements are present, the participant is ineligible * Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease * Has known history of, or active, neurologic paraneoplastic syndrome * Has an active infection requiring systemic therapy, with exceptions * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease * Has received prior systemic anticancer therapy for their locally advanced or metastatic NSCLC * Has received radiation therapy to the lung that is \>30 Gray within 6 months of start of study intervention * Has received radiotherapy to non-central nervous system (CNS) disease within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not required corticosteroids, and not have had radiation pneumonitis * Has known active CNS metastases and/or carcinomatous meningitis * Known additional malignancy that is progressing or has required active treatment within the past 3 years * Has active autoimmune disease that has required systemic treatment in the past 2 years * Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease * Is HIV-infected and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has history of allogenic tissue/solid organ transplant * Has not fully recovered from any effects of major surgical procedure