Encouraging progression-free survival and overall survival profile
Safety findings consistent with previously reported data, no new safety signals observed
REDWOOD CITY, CA, USA I October 23, 2024 I Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, today announced encouraging antitumor activity and safety/tolerability data for RMC-6236, its RAS(ON) multi-selective inhibitor, in patients with previously treated pancreatic ductal adenocarcinoma (PDAC). These updated results were presented during a late-breaking poster session at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, October 23-25, 2024.
“The maturing data reported today continue to solidify the compelling progression-free survival and overall survival for patients with pancreatic cancer treated with RMC-6236, our oral RAS(ON) multi-selective inhibitor, in the Phase 1 study,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “These results support our ongoing Phase 3 registrational study, RASolute 302, and our belief that RMC-6236 monotherapy could potentially become an important therapeutic option for patients living with advanced or metastatic pancreatic cancer.”
The RMC-6236-001 Phase 1/1b study is a multicenter, open-label, dose-escalation and dose-expansion study designed to evaluate RMC-6236 as monotherapy in patients with advanced solid tumors harboring RAS mutations or wild-type RAS. As of the July 23, 2024 data cutoff date, a total of 127 patients previously treated for PDAC were treated with RMC-6236 at doses ranging from 160 mg to 300 mg once daily (QD).
RMC-6236 appeared to be generally well tolerated at dose levels ranging from 160 mg to 300 mg QD and showed an overall safety profile consistent with previously reported results. No new safety signals were observed. The most common treatment-related adverse events (TRAEs) were rash and GI-related toxicities that were primarily Grade 1 or 2 in severity. The most common reported Grade ≥3 TRAEs were rash (8%), stomatitis (3%), and diarrhea (2%). TRAEs leading to dose modification occurred in 35% of patients with no treatment discontinuations due to TRAE. The average dose intensity across doses ranging from 160 mg to 300 mg was 92%.
RMC-6236 demonstrated durable antitumor activity as evidenced by updated progression-free survival (PFS) and overall survival (OS) at daily doses ranging from 160 mg to 300 mg, as described below. Patients with PDAC harboring a KRAS G12X mutation in the second-line (2L) setting achieved a median PFS of 8.5 months (95% confidence interval (CI), 5.3 – 11.7 months) and a median OS of 14.5 months (95% CI, 8.8 – not-estimable (NE)). Patients with PDAC harboring any RAS mutation in the 2L setting achieved a median PFS of 7.6 months (95% CI, 5.9 – 11.1 months) and a median OS of 14.5 months (95% CI, 8.8 – NE). Landmark OS for these patients at 6 months was 89% and 91% in patients with PDAC harboring a KRAS G12X mutation and patients with PDAC harboring any RAS mutation, respectively. The objective response rate for patients with tumors harboring KRAS G12X mutations was 29% in the 2L group and 22% in the third-line and beyond (3L+) group. The disease control rate was 91% and 89% in these patients, respectively.
“Pancreatic cancer remains one of the highest unmet needs in medicine. It is the most RAS-mutated of all major cancers with more than 90% of patients having tumors that harbor a RAS mutation,” said Brian M. Wolpin, M.D., M.P.H., professor of medicine at Harvard Medical School, and director of the Gastrointestinal Cancer Center and Robert T. & Judith B. Hale Chair in Pancreatic Cancer at Dana-Farber Cancer Institute, principal investigator for the RMC-6236-001 study and lead author of the ENA presentation. “To see the level of clinical activity at doses with manageable tolerability demonstrated in this Phase 1 study is very exciting, providing much needed hope for patients with this difficult to treat cancer.”
Investor Webcast
Revolution Medicines will host an investor webcast on Friday, October 25, 2024 at 6:00 p.m. Central European Standard Time to discuss the RMC-6236 and RMC-9805 monotherapy data in PDAC presented at the EORTC-NCI-AACR (“Triple”) meeting. To participate in the live webcast, participants may register in advance here. A live webcast of the call will be available on the Investors section of Revolution Medicines’ website at https://ir.revmed.com/events-and-presentations. Following the live webcast, a replay will be available on the company’s website for at least 14 days.
About Pancreatic Cancer and Pancreatic Ductal Adenocarcinoma
Pancreatic cancer is one of the most lethal malignancies, characterized by its typically late-stage diagnosis, resistance to standard chemotherapy, and high mortality rate. In the U.S., recent estimates indicate that in 2024, approximately 60,000 people will be diagnosed with pancreatic cancer, and about 50,000 people will die from this aggressive disease.
The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) and its variants, accounts for approximately 92% of all pancreatic cancer cases. Due to the lack of early symptoms and detection methods, approximately 80% of patients are diagnosed with PDAC at an advanced or metastatic stage. It is the most RAS-addicted of all major cancers, and more than 90% of patients have tumors that harbor RAS mutations. Metastatic PDAC remains one of the most common causes of cancer-related deaths in the U.S., with a five-year survival rate of approximately 3%.
About RMC-6236
RMC-6236 is an oral, direct RAS(ON) multi-selective inhibitor with the potential to help address a wide range of cancers driven by oncogenic RAS mutations. RMC-6236 suppresses RAS signaling by blocking the interaction of RAS(ON) with its downstream effectors. It does so across oncogenic RAS mutations G12X, G13X and Q61X, in major cancers including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).
About Revolution Medicines, Inc.
Revolution Medicines is a clinical-stage oncology company developing novel targeted therapies for RAS-addicted cancers. The company’s R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company’s RAS(ON) inhibitors RMC-6236, a RAS(ON) multi-selective inhibitor, RMC-6291, a RAS(ON) G12C-selective inhibitor, and RMC-9805, a RAS(ON) G12D-selective inhibitor, are currently in clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-5127 (G12V), RMC-0708 (Q61H) and RMC-8839 (G13C), in addition to RAS companion inhibitors RMC-4630 and RMC-5552.
SOURCE: Revolution Medicines
Post Views: 104
Encouraging progression-free survival and overall survival profile
Safety findings consistent with previously reported data, no new safety signals observed
REDWOOD CITY, CA, USA I October 23, 2024 I Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, today announced encouraging antitumor activity and safety/tolerability data for RMC-6236, its RAS(ON) multi-selective inhibitor, in patients with previously treated pancreatic ductal adenocarcinoma (PDAC). These updated results were presented during a late-breaking poster session at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, October 23-25, 2024.
“The maturing data reported today continue to solidify the compelling progression-free survival and overall survival for patients with pancreatic cancer treated with RMC-6236, our oral RAS(ON) multi-selective inhibitor, in the Phase 1 study,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “These results support our ongoing Phase 3 registrational study, RASolute 302, and our belief that RMC-6236 monotherapy could potentially become an important therapeutic option for patients living with advanced or metastatic pancreatic cancer.”
The RMC-6236-001 Phase 1/1b study is a multicenter, open-label, dose-escalation and dose-expansion study designed to evaluate RMC-6236 as monotherapy in patients with advanced solid tumors harboring RAS mutations or wild-type RAS. As of the July 23, 2024 data cutoff date, a total of 127 patients previously treated for PDAC were treated with RMC-6236 at doses ranging from 160 mg to 300 mg once daily (QD).
RMC-6236 appeared to be generally well tolerated at dose levels ranging from 160 mg to 300 mg QD and showed an overall safety profile consistent with previously reported results. No new safety signals were observed. The most common treatment-related adverse events (TRAEs) were rash and GI-related toxicities that were primarily Grade 1 or 2 in severity. The most common reported Grade ≥3 TRAEs were rash (8%), stomatitis (3%), and diarrhea (2%). TRAEs leading to dose modification occurred in 35% of patients with no treatment discontinuations due to TRAE. The average dose intensity across doses ranging from 160 mg to 300 mg was 92%.
RMC-6236 demonstrated durable antitumor activity as evidenced by updated progression-free survival (PFS) and overall survival (OS) at daily doses ranging from 160 mg to 300 mg, as described below. Patients with PDAC harboring a KRAS G12X mutation in the second-line (2L) setting achieved a median PFS of 8.5 months (95% confidence interval (CI), 5.3 – 11.7 months) and a median OS of 14.5 months (95% CI, 8.8 – not-estimable (NE)). Patients with PDAC harboring any RAS mutation in the 2L setting achieved a median PFS of 7.6 months (95% CI, 5.9 – 11.1 months) and a median OS of 14.5 months (95% CI, 8.8 – NE). Landmark OS for these patients at 6 months was 89% and 91% in patients with PDAC harboring a KRAS G12X mutation and patients with PDAC harboring any RAS mutation, respectively. The objective response rate for patients with tumors harboring KRAS G12X mutations was 29% in the 2L group and 22% in the third-line and beyond (3L+) group. The disease control rate was 91% and 89% in these patients, respectively.
“Pancreatic cancer remains one of the highest unmet needs in medicine. It is the most RAS-mutated of all major cancers with more than 90% of patients having tumors that harbor a RAS mutation,” said Brian M. Wolpin, M.D., M.P.H., professor of medicine at Harvard Medical School, and director of the Gastrointestinal Cancer Center and Robert T. & Judith B. Hale Chair in Pancreatic Cancer at Dana-Farber Cancer Institute, principal investigator for the RMC-6236-001 study and lead author of the ENA presentation. “To see the level of clinical activity at doses with manageable tolerability demonstrated in this Phase 1 study is very exciting, providing much needed hope for patients with this difficult to treat cancer.”
Investor Webcast
Revolution Medicines will host an investor webcast on Friday, October 25, 2024 at 6:00 p.m. Central European Standard Time to discuss the RMC-6236 and RMC-9805 monotherapy data in PDAC presented at the EORTC-NCI-AACR (“Triple”) meeting. To participate in the live webcast, participants may register in advance here. A live webcast of the call will be available on the Investors section of Revolution Medicines’ website at https://ir.revmed.com/events-and-presentations. Following the live webcast, a replay will be available on the company’s website for at least 14 days.
About Pancreatic Cancer and Pancreatic Ductal Adenocarcinoma
Pancreatic cancer is one of the most lethal malignancies, characterized by its typically late-stage diagnosis, resistance to standard chemotherapy, and high mortality rate. In the U.S., recent estimates indicate that in 2024, approximately 60,000 people will be diagnosed with pancreatic cancer, and about 50,000 people will die from this aggressive disease.
The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) and its variants, accounts for approximately 92% of all pancreatic cancer cases. Due to the lack of early symptoms and detection methods, approximately 80% of patients are diagnosed with PDAC at an advanced or metastatic stage. It is the most RAS-addicted of all major cancers, and more than 90% of patients have tumors that harbor RAS mutations. Metastatic PDAC remains one of the most common causes of cancer-related deaths in the U.S., with a five-year survival rate of approximately 3%.
About RMC-6236
RMC-6236 is an oral, direct RAS(ON) multi-selective inhibitor with the potential to help address a wide range of cancers driven by oncogenic RAS mutations. RMC-6236 suppresses RAS signaling by blocking the interaction of RAS(ON) with its downstream effectors. It does so across oncogenic RAS mutations G12X, G13X and Q61X, in major cancers including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).
About Revolution Medicines, Inc.
Revolution Medicines is a clinical-stage oncology company developing novel targeted therapies for RAS-addicted cancers. The company’s R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company’s RAS(ON) inhibitors RMC-6236, a RAS(ON) multi-selective inhibitor, RMC-6291, a RAS(ON) G12C-selective inhibitor, and RMC-9805, a RAS(ON) G12D-selective inhibitor, are currently in clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-5127 (G12V), RMC-0708 (Q61H) and RMC-8839 (G13C), in addition to RAS companion inhibitors RMC-4630 and RMC-5552.
SOURCE: Revolution Medicines
Post Views: 104
