Revolution Medicines Presents Updated Data from RMC-6236 Monotherapy Study in Patients with Advanced Pancreatic Ductal Adenocarcinoma
Revolution Medicines announced encouraging data for RMC-6236, its RAS(ON) multi-selective inhibitor, in treating pancreatic ductal adenocarcinoma (PDAC). The Phase 1/1b study included 127 patients treated with doses ranging from 160mg to 300mg daily. Key results showed median progression-free survival of 8.5 months and overall survival of 14.5 months in second-line KRAS G12X mutation patients. The treatment demonstrated a 29% objective response rate in second-line patients and showed manageable safety profile with primarily Grade 1 or 2 adverse events. The most common side effects were rash and GI-related toxicities, with no treatment discontinuations due to adverse events.
Revolution Medicines ha annunciato dati incoraggianti per RMC-6236, il suo inibitore multi-selettivo RAS(ON), nel trattamento dell'adenocarcinoma duttale pancreatico (PDAC). Lo studio di Fase 1/1b ha incluso 127 pazienti trattati con dosi che variavano da 160mg a 300mg al giorno. I risultati chiave hanno mostrato una sopravvivenza libera da progressione mediana di 8,5 mesi e una sopravvivenza complessiva di 14,5 mesi nei pazienti con mutazione KRAS G12X di seconda linea. Il trattamento ha dimostrato un 29% di tasso di risposta obiettiva nei pazienti di seconda linea e ha mostrato un profilo di sicurezza gestibile, con eventi avversi principalmente di Grado 1 o 2. Gli effetti collaterali più comuni erano eruzione cutanea e tossicità gastrointestinali, senza interruzioni del trattamento a causa di eventi avversi.
Revolution Medicines anunció datos alentadores para RMC-6236, su inhibidor multi-selectivo RAS(ON), en el tratamiento del adenocarcinoma ductal pancreático (PDAC). El estudio de Fase 1/1b incluyó 127 pacientes tratados con dosis que variaban de 160mg a 300mg diarios. Los resultados clave mostraron una supervivencia libre de progresión mediana de 8.5 meses y una supervivencia general de 14.5 meses en pacientes con mutación KRAS G12X en segunda línea. El tratamiento demostró un 29% de tasa de respuesta objetiva en pacientes de segunda línea y mostró un perfil de seguridad manejable, con eventos adversos principalmente de Grado 1 o 2. Los efectos secundarios más comunes fueron erupción cutánea y toxicidades gastrointestinales, sin interrupciones del tratamiento debido a eventos adversos.
Revolution Medicines는 췌장관 선암(PDAC) 치료를 위한 다중 선택적 RAS(ON) 억제제 RMC-6236에 대한 고무적인 데이터를 발표했습니다. 1/1b상 시험에는 127명의 환자가 포함되었으며, 치료용량은 하루 160mg에서 300mg까지 다양했습니다. 주요 결과는 KRAS G12X 변이를 가진 2차 환자에서 중위 무진행 생존 기간이 8.5개월, 전반적인 생존 기간이 14.5개월인 것으로 나타났습니다. 치료는 2차 환자에서 29%의 객관적 반응률을 보였고, 주로 1도 또는 2도의 불리한 사건으로 관리 가능한 안전성 프로필을 보여주었습니다. 가장 흔한 부작용은 발진과 위장 관련 독성이었으며, 불리한 사건으로 인한 치료 중단은 없었습니다.
Revolution Medicines a annoncé des données encourageantes pour RMC-6236, son inhibiteur multi-sélectif RAS(ON), dans le traitement de l'adénocarcinome canalaire pancréatique (PDAC). L'étude de Phase 1/1b a inclus 127 patients traités avec des doses variant de 160mg à 300mg par jour. Les résultats clés ont montré une survie sans progression médiane de 8,5 mois et une survie globale de 14,5 mois chez les patients avec mutation KRAS G12X en seconde ligne. Le traitement a démontré un taux de réponse objective de 29% chez les patients de seconde ligne et a montré un profil de sécurité gérable avec des événements indésirables principalement de Grade 1 ou 2. Les effets secondaires les plus courants étaient des éruptions cutanées et des toxicités gastro-intestinales, sans interruptions de traitement dues à des événements indésirables.
Revolution Medicines hat ermutigende Daten zu RMC-6236, ihrem multi-selektiven RAS(ON)-Inhibitor, bei der Behandlung des duktalen Adenokarzinoms der Bauchspeicheldrüse (PDAC) veröffentlicht. Die Phase 1/1b-Studie umfasste 127 Patienten, die mit Dosen von 160mg bis 300mg täglich behandelt wurden. Die wichtigsten Ergebnisse zeigten ein medianes progressionsfreies Überleben von 8,5 Monaten und ein Gesamtüberleben von 14,5 Monaten bei Patienten mit KRAS G12X-Mutation in der zweiten Linie. Die Behandlung zeigte eine 29%-ige objektive Ansprechrate bei Patienten in zweiter Linie und wies ein handhabbares Sicherheitsprofil mit hauptsächlich Grad 1 oder 2 unerwünschten Ereignissen auf. Die häufigsten Nebenwirkungen waren Hautausschlag und gastrointestinale Toxizitäten, ohne Therapieabbrechungen aufgrund unerwünschter Ereignisse.
- Strong survival data with 14.5 months median overall survival in second-line PDAC patients
- High disease control rate of 91% in second-line patients
- 29% objective response rate in second-line KRAS G12X mutation patients
- 92% average dose intensity maintained across treatment doses
- No treatment discontinuations due to adverse events
- 35% of patients required dose modifications due to treatment-related adverse events
- 8% of patients experienced Grade ≥3 rash as side effect
Insights
The clinical trial data for RMC-6236 shows remarkably promising results in treating pancreatic cancer, one of the most challenging oncological conditions. The median progression-free survival of 8.5 months and median overall survival of 14.5 months in second-line PDAC patients with KRAS G12X mutations are particularly noteworthy. The disease control rate of 91% in second-line treatment is exceptional for pancreatic cancer.
The safety profile appears manageable, with mostly Grade 1-2 adverse events and minimal treatment discontinuations. The 92% average dose intensity indicates strong tolerability. These results are especially significant given that pancreatic cancer typically has poor treatment outcomes and therapeutic options. The data strongly supports the ongoing Phase 3 trial and suggests potential breakthrough status in PDAC treatment.
Encouraging progression-free survival and overall survival profile
Safety findings consistent with previously reported data, no new safety signals observed
Investor webcast to be held Friday, October 25 at 12:00 p.m. Eastern Time (ET)
REDWOOD CITY, Calif., Oct. 23, 2024 (GLOBE NEWSWIRE) -- 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 (
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 (
“Pancreatic cancer remains one of the highest unmet needs in medicine. It is the most RAS-mutated of all major cancers with more than
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
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.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered "forward-looking statements," including without limitation statements regarding progression of clinical studies and findings from these studies, including the safety, tolerability and antitumor activity of the company’s candidates being studied and the durability of these results; dosing and enrollment in the company’s clinical trials; and the company’s belief that RMC-6236 could become a therapeutic option for pancreatic cancer patients. Forward-looking statements are typically, but not always, identified by the use of words such as "may," "will," "would," "believe," "intend," "plan," "anticipate," "estimate," "expect," and other similar terminology indicating future results. Such forward-looking statements are subject to substantial risks and uncertainties that could cause the company’s development programs, future results, performance or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include without limitation risks and uncertainties inherent in the drug development process, including the company’s programs’ current stage of development, the process of designing and conducting preclinical and clinical trials, risks that the results of prior clinical trials may not be predictive of future clinical trials, clinical efficacy, or other future results, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, the company’s ability to successfully establish, protect and defend its intellectual property, other matters that could affect the sufficiency of the company’s capital resources to fund operations, reliance on third parties for manufacturing and development efforts, changes in the competitive landscape, and the effects on the company’s business of the global events, such as international conflicts or global pandemics. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Revolution Medicines in general, see Revolution Medicines’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on August 7, 2024, and its future periodic reports to be filed with the SEC. Except as required by law, Revolution Medicines undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events.
FAQ
What were the survival results for RMC-6236 in PDAC patients with KRAS G12X mutations?
What was the objective response rate for RVMD's RMC-6236 in PDAC patients?
What were the main side effects of RMC-6236 in the Phase 1/1b trial?