Overview
This study aims to assess 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 a PD-L1 expression < 1% regardless of STK11 mutation status (cohort A), or a PD-L1 expression ≥ 1% and an STK11 co-mutation (cohort B).
Description
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 (Cohort A and B) that will recruit participants in parallel.
The study treatment begins on Cycle 1 Day 1 (C1D1) with the first administration of JDQ443. Each cycle is 21 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
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).
- Know active (unstable/symptomatic) 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
