NCT05445843: KontRASt-06

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.

Active, enrolled Phase 2 Results posted Last updated 13 February 2026

What this trial tests

Phase 2 trial testing JDQ443 in 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 in 95 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

6 December 2022

Primary endpoint
4 November 2024

31 December 2026

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	95
Start date	6 December 2022
Primary completion	4 November 2024
Estimated completion	31 December 2026
Sites	45 locations across Belgium, Greece, United States, Hungary, Germany, Spain, United Kingdom, France

Drugs / interventions tested

• JDQ443 — full drug profile →

Conditions studied

• 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 — all drugs for 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 →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 100, any sex, with 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. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials.
   Xie X, Yu T, Li X, Zhang N, et al · · 2023 · cited 246× · PMID 37669923 · DOI 10.1038/s41392-023-01589-z
2. Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.
   Yin G, Huang J, Petela J, Jiang H, et al · · 2023 · cited 50× · PMID 37221195 · DOI 10.1038/s41392-023-01441-4
3. MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer.
   Casacuberta-Serra S, González-Larreategui Í, Capitán-Leo D, Soucek L. · · 2024 · cited 43× · PMID 39164274 · DOI 10.1038/s41392-024-01907-z
4. The Therapeutic Landscape for <i>KRAS</i>-Mutated Colorectal Cancers.
   Tria SM, Burge ME, Whitehall VLJ. · · 2023 · cited 33× · PMID 37190303 · DOI 10.3390/cancers15082375
5. New Generations of Tyrosine Kinase Inhibitors in Treating NSCLC with Oncogene Addiction: Strengths and Limitations.
   Attili I, Corvaja C, Spitaleri G, Del Signore E, et al · · 2023 · cited 32× · PMID 37894445 · DOI 10.3390/cancers15205079
6. Emerging Pharmacotherapeutic Strategies to Overcome Undruggable Proteins in Cancer.
   Lu Y, Yang Y, Zhu G, Zeng H, et al · · 2023 · cited 24× · PMID 37496997 · DOI 10.7150/ijbs.83026
7. Direct GDP-KRAS^G12C inhibitors and mechanisms of resistance: the tip of the iceberg.
   Rosen JC, Sacher A, Tsao MS. · · 2023 · cited 15× · PMID 36950276 · DOI 10.1177/17588359231160141
8. Current status of KRAS G12C inhibitors in NSCLC and the potential for combination with anti-PD-(L)1 therapy: a systematic review.
   Zhang F, Wang B, Wu M, Zhang L, et al · · 2025 · cited 9× · PMID 40303413 · DOI 10.3389/fimmu.2025.1509173