vociprotafib (RMC-4630) / Revolution Medicines - LARVOL DELTA

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1 | N=610 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting | N=1200 ➔ 610 | Trial primary completion date: Jun 2026 ➔ Dec 2026

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

SHP2 inhibition with RMC4630 demonstrates antitumor efficacy and potentiates nanoparticle-paclitaxel response in pancreatic cancer (AACR 2025) - "The combination of nab-paclitaxel and gemcitabine (NPT-GEM) remains the standard treatment for advanced and metastatic PDAC, achieving a median survival of approximately 8.5 months. These findings underscore the therapeutic potential of RMC4630, especially in combination with standard chemotherapy, as a promising approach for managing KRAS-mutant PDAC."

Clinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CASP3 • KRAS

RMC-4630-03: Combination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies (clinicaltrials.gov) - P2 | N=47 | Completed | Sponsor: Revolution Medicines, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ Aug 2024 | Trial primary completion date: Sep 2023 ➔ Jul 2024

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

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1 | N=1200 | Recruiting | Sponsor: Amgen | Trial completion date: Mar 2028 ➔ Dec 2027

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

SHERPA: Combination Therapy of RMC-4630 and LY3214996 in Metastatic KRAS Mutant Cancers (clinicaltrials.gov) - P1 | N=24 | Terminated | Sponsor: The Netherlands Cancer Institute | N=55 ➔ 24 | Recruiting ➔ Terminated | Trial primary completion date: Jan 2024 ➔ Jul 2024; Due to a lack of safety and efficacy.

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

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1 | N=1200 | Recruiting | Sponsor: Amgen | Trial completion date: Jun 2029 ➔ Mar 2028 | Trial primary completion date: Jan 2027 ➔ Apr 2026

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Brain Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1 | N=1200 | Recruiting | Sponsor: Amgen | Trial completion date: Mar 2028 ➔ Jun 2029 | Trial primary completion date: Sep 2025 ➔ Jan 2027

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Brain Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1 | N=1200 | Recruiting | Sponsor: Amgen | Trial primary completion date: Dec 2026 ➔ Sep 2025

Combination therapy • Metastases • Monotherapy • Trial primary completion date • Brain Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1 | N=1200 | Recruiting | Sponsor: Amgen | Phase classification: P1/2 ➔ P1

Combination therapy • Metastases • Monotherapy • Phase classification • Brain Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1/2 | N=1126 | Recruiting | Sponsor: Amgen | Trial primary completion date: Sep 2026 ➔ Dec 2026

Combination therapy • Metastases • Monotherapy • Trial primary completion date • Brain Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies (clinicaltrials.gov) - P1/2 | N=65 | Terminated | Sponsor: Sanofi | Active, not recruiting ➔ Terminated; Sponsor's decision not related to any safety concern

Combination therapy • Metastases • Trial termination • Non Small Cell Lung Cancer • Oncology • BRAF • KRAS • NF1

Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies (clinicaltrials.gov) - P1/2 | N=65 | Active, not recruiting | Sponsor: Sanofi | Trial completion date: Jul 2024 ➔ Mar 2024 | Trial primary completion date: Jul 2024 ➔ Mar 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Non Small Cell Lung Cancer • Oncology • BRAF • KRAS • NF1

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1/2 | N=1143 | Recruiting | Sponsor: Amgen | Phase classification: P1b/2 ➔ P1/2

Phase classification • Brain Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • KRAS

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1/2 | N=1143 | Recruiting | Sponsor: Amgen | Trial primary completion date: Jun 2026 ➔ Sep 2026

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

Phase I/Ib study of SHP2-ERK inhibition in KRASm pancreatic cancer (SHERPA trial) and preclinical identification of potential resistance markers (ESMO 2023) - P1 | "The aim of this phase I/Ib trial is to assess safety and efficacy of treatment with SHP2 inhibitor RMC-4630 and ERK inhibitor LY3214996 in KRASm PDAC, non-small cell lung carcinoma (NSCLC) and colorectal carcinoma (CRC) patients. The RP2D has not been determined yet. Alterations in the PI3K/AKT/mTOR and the c-JUN pathways could be markers for drug resistance, which data are pending."

P1 data • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • JUN • KRAS • PTEN

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1b/2 | N=1143 | Recruiting | Sponsor: Amgen | Trial completion date: Jul 2027 ➔ Oct 2027

Combination therapy • Metastases • Monotherapy • Trial completion date • Brain Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • KRAS

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1b/2 | N=1143 | Recruiting | Sponsor: Amgen | Trial primary completion date: Jan 2025 ➔ May 2026

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

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1b/2 | N=1143 | Recruiting | Sponsor: Amgen | Trial completion date: Jan 2029 ➔ Jul 2027 | Trial primary completion date: Jul 2026 ➔ Jan 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Brain Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • KRAS

Revolution Medicines Reports Second Quarter 2023 Financial Results and Update on Corporate Progress (GlobeNewswire) - "The RMC-4630-03 study is fully enrolled, and the company plans to review a complete data set from the study when available. Decisions about future development of RMC-4630 will take into account this analysis and other considerations, including the potential of RMC-6236 as a RAS Companion Inhibitor. The company no longer plans to share topline data from the RMC-4630-03 study prior to disclosing decisions about future development of the compound."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Dose-Esc/Exp RMC4630 & Cobi in Relapsed/Refractory Solid Tumors & RMC4630& Osi in EGFR+ Locally Adv/Meta NSCLC (clinicaltrials.gov) - P1/2 | N=113 | Completed | Sponsor: Revolution Medicines, Inc. | Phase classification: P1b/2 ➔ P1/2

Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • EGFR • KRAS • NF1

Sotorasib in Combination with RMC-4630, a SHP2 Inhibitor, in KRAS p.G12C-Mutated NSCLC and Other Solid Tumors (IASLC-WCLC 2022) - " As of January 17, 2022, 21 patients (11-NSCLC, 6-CRC, and 4-other solid tumors) who had received a median of 2 prior lines of therapy (range, 1-6) were enrolled; 10 patients (48%) had received prior KRASG12C inhibitor therapy (8-sotorasib, 2-adagrasib). The combination of sotorasib with RMC-4630 was safe and tolerable in patients with KRAS p.G12C-mutated solid tumors. Promising clinical activity was observed in KRAS p.G12C-mutated NSCLC patients, most notably in those KRASG12C inhibitor-naïve. Dose expansion is underway to further define efficacy and safety in both KRASG12C inhibitor-naïve and KRASG12C inhibitor-exposed NSCLC patients."

Combination therapy • Cardiovascular • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hypertension • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pulmonary Disease • Respiratory Diseases • Solid Tumor • KRAS

A next-generation KRASG12C inhibitor ABSK071 demonstrated broad synergy with other therapeutic agents in KRASG12C mutated cancer models (AACR 2023) - "A set of immuno-oncology reagents, including anti-PD-1/L1, CSF-1R inhibitor (ABSK021) and CD73 inhibitor (ABSK051) were also tested in combination with ABSK071 in vivo using mouse syngeneic models. ABSK071 demonstrated much stronger inhibitory activity than sotorasib and adagrasib against a variety of cell lines harboring KRASG12C, as well as significantly better in vivo anti-tumor efficacy in xenograft models that were less sensitive to sotorasib. Synergistic effects on cell growth inhibition were observed in vitro with ABSK071 in combination with several agents including cetuximab, afatinib, AZD4547, TNO-155, RMC-4630 and BI3406... ABSK071 is a next-generation KRASG12C inhibitor with greater activity and anti-tumor efficacy in vitro and in vivo. It also demonstrated broad synergistic effects with a large set of targeted agents and immuno-oncology agents, indicating its strong potential in combinatory therapy in treating a wider range of KRASG12C-dependent cancers."

IO biomarker • Late-breaking abstract • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

RMC-4630-03: Combination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies (clinicaltrials.gov) - P2 | N=47 | Active, not recruiting | Sponsor: Revolution Medicines, Inc. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2023 ➔ Sep 2023

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

CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) - P1b/2 | N=1143 | Recruiting | Sponsor: Amgen | Trial completion date: Apr 2028 ➔ Jan 2029 | Trial primary completion date: Feb 2026 ➔ Jul 2026

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Brain Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • KRAS

Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies (clinicaltrials.gov) - P1/2 | N=65 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting | N=133 ➔ 65 | Trial completion date: Jan 2025 ➔ Jul 2024 | Trial primary completion date: Jan 2025 ➔ Jul 2024

Combination therapy • Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • KRAS • NF1