opnurasib (JDQ443) / Novartis - LARVOL DELTA

KontRASt-01: Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=344 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2026 ➔ Jan 2027 | Trial primary completion date: Aug 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

KontRASt-R: Rollover Study for Participants Who Have Been Treated With and Are Continuing to Benefit From Opnurasib as a Single Agent or in Combination With Other Study Treatments (clinicaltrials.gov) - P1/2 | N=40 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

KontRASt-03: Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=74 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: May 2026 ➔ Nov 2026 | Trial primary completion date: Apr 2026 ➔ Oct 2026

Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

KontRASt-01 update: Safety and efficacy of JDQ443 in KRAS G12C-mutated solid tumors including non-small cell lung cancer (NSCLC). (ASCO 2023) - P1/2 | "JDQ443 demonstrates an acceptable safety and tolerability profile at 200 mg BID, with clinical activity in pts with NSCLC. Enrollment is ongoing to the JDQ443 monotherapy DEx and the JDQ443 + TNO155 and JDQ443 + tislelizumab combination arms. Clinical trial information: NCT04699188."

Clinical • IO biomarker • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Lung Cancer • Musculoskeletal Pain • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • KRAS

KontRASt-01: Preliminary Safety and Efficacy of JDQ443 + TNO155 in Patients with Advanced, KRAS G12C-Mutated Solid Tumors (IASLC-WCLC 2023) - P1/2 | "JDQ443+TNO155 was tolerated with notable toxicities of edema, cytopenias, and fatigue. MTD was not reached; the RD for further evaluation was selected based on collective safety, pharmacokinetics, and efficacy. Preliminary anti-tumor activity was observed, including in KRASG12C inhibitor previously-treated NSCLC."

Clinical • Metastases • Anemia • Fatigue • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia • KRAS

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. (clinicaltrials.gov) - P2 | N=95 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Nov 2027 ➔ Dec 2026

IO biomarker • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1 • STK11

KontRASt-03: Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=74 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2025 ➔ May 2026 | Trial primary completion date: Nov 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Phase 1 Study to Evaluate the Pharmacokinetics of JDQ443 in Participants With Hepatic Impairment Compared to Matched Healthy Control Participants. (clinicaltrials.gov) - P1 | N=33 | Completed | Sponsor: Novartis Pharmaceuticals | Terminated ➔ Completed

Trial completion • Hepatology • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Profiling opnurasib (JDQ-443) for the treatment of non-small cell lung cancer (NSCLC). (PubMed, Expert Opin Pharmacother) - "Oral small molecule inhibitors, including sotorasib and adagrasib, have demonstrated moderate efficacy in targeting KRAS G12C in NSCLC. In the face of an expanding market, development of JDQ-443 has been halted despite promising safety and efficacy outcomes and ongoing innovative trials, highlighting critical challenges in the drug development process. The existing body of work characterizing JDQ-443 remains extremely informative."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Multicenter study of the impact of trial eligibility criteria on enrollment to KRAS G12C inhibitor trials in patients with non-small cell lung cancer. (ASCO 2025) - " We extracted EC for Phase I-III trials of six KRAS G12C inhibitors (sotorasib, adagrasib, olomorasib, divarasib, JDQ443 and RMC-6291) that were published or made available by sponsors. Our data indicate substantial differences between the real-world population of patients treated with KRAS G12C inhibitors and those who were trial eligible. Efforts should focus on improving clinical trial generalizability without compromising safety."

Clinical • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • KRAS

KontRASt-02: Study of JDQ443 in Comparison With Docetaxel in Participants With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=96 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2025 ➔ Mar 2026 | Trial primary completion date: Oct 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

KontRASt-01: Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=344 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Apr 2026 ➔ Aug 2026 | Trial primary completion date: Apr 2026 ➔ Aug 2026

Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Clinical spectrum and outcomes of KRAS mutated advanced stage NSCLC (ELCC 2025) - "KRAS inhibitors (sotorasib or opnurasib) were given in 18 (26%) G12C pts, with a median PFS of 7.6 mo. In real-world 98% of pts with stage IV KRAS mutant NSCLC received first-line therapy and 53% received further line therapy. In real-world 98% of pts with stage IV KRAS mutant NSCLC received first-line therapy and 53% received further line therapy. There was no influence of KRAS subtype (G12C vs non-G12C) on OS. At disease progression, a median PFS 5.2 mo for docetaxel-treated and 7.6mo for oral KRASi-treated was noted in KRAS G12C pts."

Clinical • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

KontRASt-02: Study of JDQ443 in Comparison With Docetaxel in Participants With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=96 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: May 2025 ➔ Oct 2025 | Trial primary completion date: May 2025 ➔ Oct 2025

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Neoadjuvant Platform Trial in Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=4 | Active, not recruiting | Sponsor: Canadian Cancer Trials Group | Recruiting ➔ Active, not recruiting | N=27 ➔ 4

Enrollment change • Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

KontRASt-03: Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=74 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Apr 2025 ➔ Nov 2025

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

KontRASt-01: Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=344 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2025 ➔ Apr 2026 | Trial primary completion date: Aug 2025 ➔ Apr 2026

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

KontRASt-01: Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=344 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Mar 2026 ➔ Aug 2025 | Trial primary completion date: Mar 2026 ➔ Aug 2025

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

KontRASt-02: Study of JDQ443 in Comparison With Docetaxel in Participants With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=95 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Sep 2024 ➔ May 2025

Metastases • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

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. (clinicaltrials.gov) - P2 | N=96 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Nov 2026 ➔ Nov 2024

IO biomarker • Metastases • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1 • STK11

KontRASt-01: Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=344 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2027 ➔ Mar 2026 | Trial primary completion date: Jan 2027 ➔ Mar 2026

Enrollment closed • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Phase II Study of Neoadjuvant Opnurasib KRAS G12C Inhibitor in Patients With Surgically Resectable Non-Small Cell Lung Cancer (CCTG IND.242A): A Substudy of the IND.242 Platform Master Protocol. (PubMed, Clin Lung Cancer) - "Secondary objectives include safety and tolerability of the treatment regimen, objective response rate (ORR) by RECIST 1.1 for the neoadjuvant treatment period, pathological complete response (pCR) rate, event-free survival (EFS) at 2 years, and surgical outcomes. Exploratory objectives are to explore patient related outcomes (PROs) and identify potential predictive biomarkers of response and mechanisms of resistance on tissue and peripheral blood samples."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • KRAS

A Phase 1 Study to Evaluate the Pharmacokinetics of JDQ443 in Participants With Hepatic Impairment Compared to Matched Healthy Control Participants. (clinicaltrials.gov) - P1 | N=33 | Terminated | Sponsor: Novartis Pharmaceuticals | N=48 ➔ 33 | Trial completion date: Aug 2024 ➔ Apr 2024 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2024 ➔ Apr 2024; Sponsor Decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hepatology • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

KontRASt-03: Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=74 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | N=346 ➔ 74

Enrollment change • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

KontRASt-03: Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov) - P1/2 | N=346 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2027 ➔ May 2025 | Trial primary completion date: May 2027 ➔ Mar 2025

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS