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. (KontRASt-06)

Novartis

Status and phase: Active, not recruiting; Phase 2

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

Treatments: Drug: JDQ443

Study type: Interventional

Funder types: Industry

Identifiers

NCT05445843

2024-511708-18-00 (Registry Identifier)

CJDQ443B12201

Details and patient eligibility

About

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).

Full 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 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.
• Cohort B: participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation.

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.

Enrollment: 95 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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95 participants in 2 patient groups

Cohort A- PD-L1<1%

Experimental group

Description:

Participants whose tumors harbor a KRAS G12C mutation and a PD-L1 expression \< 1%, regardless of STK11 mutation status.

Treatment:

Drug: JDQ443

Cohort B- PD-L1≥ 1% and STK11 mutation

Experimental group

Description:

Participants whose tumors harbor a KRAS G12C mutation, a PD-L1 expression ≥ 1% and an STK11 co-mutation.

Treatment:

Drug: JDQ443