opnurasib (JDQ443) / Novartis - LARVOL DELTA

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

Impact of trial eligibility criteria on enrollment to KRAS G12C inhibitor trials in patients with non-small cell lung cancer. (ASCO 2024) - " We extracted EC for Phase I-III trials among six KRAS G12C inhibitors: sotorasib, adagrasib, LY3537982 , divarasib, JDQ443 and RMC-6291. Our findings suggest that most patients with KRAS G12C mutations would not have been eligible for relevant trials, including > 75% of patients who received KRAS G12C inhibitors off-trial after accelerated FDA approval. EC did not expand after early phase trials demonstrated evidence of safety. These data should guide sponsor and FDA considerations in the development of trial protocols for targeted therapies, as fewer barriers to trial participation would enable trials to be completed more quickly and would improve the generalizability of trial results."

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=95 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2025 ➔ May 2025 | Trial primary completion date: Apr 2025 ➔ Sep 2024

Metastases • Trial completion date • Trial primary completion date • 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 | Recruiting ➔ Active, not recruiting | N=360 ➔ 95

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