Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation.

This study aims to evaluate the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor a KRAS G12C mutation and have a PD-L1 expression \< 1% (cohort A) or a PD-L1 expression ≥ 1% and an STK11 co-mutation (cohort B).

This is a non-randomized, open-label, single-arm, multicenter, phase II study evaluating the antitumor activity and safety of JDQ443 single-agent as first-line treatment for participants with locally advanced or metastatic KRAS G12C-mutated NSCLC. The study will have 2 non-comparative cohorts that will recruit participants in parallel according to the following characteristics: * Cohort A: participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status (N=90). * Cohort B: participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation (N=30). The study treatment begins on Cycle 1 Day 1 (C1D1) with the first administration of JDQ443. One treatment cycle consists of 21 (±3) days. Study completion is defined as the earliest occurrence of one of the following: * The last participant completes last study visit (and the assessments associated with this visit have been documented and followed-up appropriately by the Investigator), dies, withdraws consent, or is lost to follow-up, whichever comes first.\] * In the event of an early study termination decision, the date of that decision. * Another clinical study becomes available that can continue to provide JDQ443 to study participants and all participants with ongoing treatment are transferred to that clinical study.

Key Inclusion criteria * Histologically confirmed locally advanced (stage IIIb/IIIc not eligible for definitive chemoradiation or surgical resection with curative intent) or metastatic (stage IV) NSCLC without previous systemic treatment for metastatic disease. Prior (neo)adjuvant treatment with chemotherapy and/or immunotherapy, or prior radiotherapy administered sequentially or concomitantly with chemotherapy and/or immunotherapy for localized or locally advanced disease are accepted if the time between therapy completion and enrollment is \> 12 months. * Presence of a KRAS G12C mutation (all participants) and: * Cohort A: PD-L1 expression \< 1%, regardless of STK11 mutation status * Cohort B: PD-L1 expression ≥ 1% and an STK11 co-mutation * At least one measurable lesion per RECIST 1.1. * ECOG performance status ≤ 1. * Participants capable of swallowing study medication. Key Exclusion criteria * Participants whose tumors harbor an EGFR-sensitizing mutation and/or ALK rearrangement by local laboratory testing. Participants with other known druggable alterations will be excluded, if required by local guidelines * Previous use of a KRAS G12C inhibitor or previous systemic treatment for metastatic NSCLC. * A medical condition that results in increased photosensitivity (i.e., solar urticaria, lupus erythematosus, etc.). * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Participants who are taking a prohibited medication (strong CYP3A inducers) that cannot be discontinued at least seven days prior to the first dose of study treatment and for the duration of the study. Other inclusion/exclusion criteria may apply