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.

Conditions: Locally Advanced or Metastatic KRAS G12C-mutated NSCLC With a PD-L1 Expression <1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation

Summary: 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.

Eligibility criteria:
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

Keywords: lung cancer nsclc kras g12c stk11 pd-l1 jdq443