Revolution Medicines Presents Initial Data from RMC-9805 Monotherapy Study in Patients with Advanced Pancreatic Ductal Adenocarcinoma
Revolution Medicines announced preliminary safety and antitumor data for RMC-9805, its RAS(ON) G12D-selective inhibitor, in patients with previously treated pancreatic ductal adenocarcinoma (PDAC). The Phase 1/1b study included 179 patients treated with varying doses. At 1200 mg daily dose, the drug showed a 30% objective response rate and 80% disease control rate. The treatment demonstrated an encouraging safety profile with primarily Grade 1 adverse events, including GI-related toxicities and rash. No Grade 4 or 5 treatment-related adverse events were observed, and no patients discontinued treatment due to adverse events.
Revolution Medicines ha annunciato dati preliminari di sicurezza e antitumorali per RMC-9805, il suo inibitore selettivo RAS(ON) G12D, in pazienti con adenocarcinoma duttale pancreatico (PDAC) precedentemente trattati. Lo studio di Fase 1/1b ha incluso 179 pazienti trattati con dosi variabili. Con una dose giornaliera di 1200 mg, il farmaco ha mostrato un 30% di tasso di risposta obiettiva e un 80% di tasso di controllo della malattia. Il trattamento ha dimostrato un profilo di sicurezza incoraggiante, con eventi avversi principalmente di Grade 1, inclusi tossicità gastrointestinali e rash. Non sono stati osservati eventi avversi correlati al trattamento di Grade 4 o 5 e nessun paziente ha interrotto il trattamento a causa di eventi avversi.
Revolution Medicines anunció datos preliminares de seguridad y antitumorales para RMC-9805, su inhibidor selectivo de RAS(ON) G12D, en pacientes con adenocarcinoma ductal pancreático (PDAC) previamente tratados. El estudio de Fase 1/1b incluyó 179 pacientes tratados con dosis variables. Con una dosis diaria de 1200 mg, el fármaco mostró un 30% de tasa de respuesta objetiva y un 80% de tasa de control de la enfermedad. El tratamiento mostró un perfil de seguridad alentador, con eventos adversos principalmente de Grado 1, incluyendo toxicidades relacionadas con el tracto gastrointestinal y erupción. No se observaron eventos adversos relacionados con el tratamiento de Grado 4 o 5, y ningún paciente interrumpió el tratamiento debido a eventos adversos.
Revolution Medicines는 이전에 치료를 받은 췌장 관 편평세포 선암(PDAC) 환자를 대상으로 RAS(ON) G12D 선택적 억제제 RMC-9805의 초기 안전성과 항종양 데이터를 발표하였습니다. 1/1b상 시험에는 179명의 환자가 다양한 용량으로 치료를 받았습니다. 하루 1200 mg의 용량에서, 이 약물은 30%의 객관적 반응률과 80%의 질병 조절률을 나타냈습니다. 치료는 주로 1등급의 부작용으로 구성된 고무적인 안전성 프로파일을 보여주었으며, 위장 관련 독성과 발진이 포함되었습니다. 4등급 또는 5등급의 치료 관련 부작용은 관찰되지 않았고, 부작용으로 인해 치료를 중단한 환자는 없었습니다.
Revolution Medicines a annoncé des résultats préliminaires sur la sécurité et l'antitumorale du RMC-9805, son inhibiteur sélectif de RAS(ON) G12D, chez des patients traités précédemment pour un adénocarcinome canalaire pancréatique (PDAC). L'étude de Phase 1/1b a inclus 179 patients traités avec diverses doses. À une dose quotidienne de 1200 mg, le médicament a montré un taux de réponse objective de 30% et un taux de contrôle de la maladie de 80%. Le traitement a démontré un profil de sécurité encourageant avec principalement des événements indésirables de Grade 1, y compris des toxicités gastrointestinales et des éruptions cutanées. Aucun événement indésirable de Grade 4 ou 5 lié au traitement n'a été observé, et aucun patient n'a interrompu le traitement en raison d'événements indésirables.
Revolution Medicines hat vorläufige Sicherheits- und antitumorale Daten für RMC-9805, seinen selektiven RAS(ON) G12D-Hemmer, bei zuvor behandelten Patienten mit duktalem Pankreaskrebs (PDAC) bekannt gegeben. Die Phase 1/1b-Studie umfasste 179 Patienten, die mit unterschiedlichen Dosen behandelt wurden. Bei einer täglichen Dosis von 1200 mg zeigte das Medikament eine 30%ige objektive Ansprechraten und eine 80%ige Krankheitskontrollrate. Die Behandlung wies ein ermutigendes Sicherheitsprofil auf, mit überwiegend Nebenwirkungen Grad 1, einschließlich GI-bezogener Toxizitäten und Hautausschlag. Es wurden keine behandlungsbedingten Nebenwirkungen der Grade 4 oder 5 beobachtet, und kein Patient brach die Behandlung aufgrund von Nebenwirkungen ab.
- 30% objective response rate achieved in PDAC patients at 1200 mg daily dose
- 80% disease control rate in treated patients
- Generally well-tolerated safety profile with primarily Grade 1 adverse events
- No patient discontinuations due to treatment-related adverse events
- Third compound from pipeline to demonstrate clinical proof-of-concept
- None.
Insights
The initial clinical data for RMC-9805 represents a significant breakthrough in treating PDAC, one of the deadliest forms of cancer. The 30% objective response rate and 80% disease control rate in previously treated patients are particularly noteworthy given the historically poor outcomes in pancreatic cancer.
The safety profile is remarkably clean, with mostly Grade 1 GI-related toxicities and minimal dose reductions or discontinuations. This tolerability profile, combined with no maximum tolerated dose being reached, suggests potential for combination therapies and longer treatment durations.
The market opportunity is substantial, with
This clinical milestone significantly derisks Revolution Medicines' RAS(ON) inhibitor platform, marking their third successful proof-of-concept compound. The positive data in PDAC, a notoriously difficult-to-treat cancer, could accelerate partnership discussions and increase the likelihood of successful commercialization.
The company's broad pipeline of RAS inhibitors targeting different mutations (G12C, G12D, G12V, Q61H, G13C) positions them as a leader in precision oncology. With a market cap of
First clinical results for RMC-9805, a RAS(ON) G12D-selective inhibitor, demonstrate encouraging tolerability and antitumor activity in patients with PDAC
Investor webcast to be held Friday, October 25 at 12:00 p.m. Eastern Time (ET)
REDWOOD CITY, Calif., Oct. 25, 2024 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, today announced preliminary safety and antitumor data for RMC-9805, its RAS(ON) G12D-selective inhibitor, in patients with previously treated pancreatic ductal adenocarcinoma (PDAC). These initial results were presented during the late-breaking oral session at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona on October 25, 2024.
“We are pleased to report the first clinical data for RMC-9805, our novel, oral RAS(ON) G12D-selective covalent inhibitor, which demonstrate encouraging initial safety, tolerability and antitumor activity evidenced by tumor regressions,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “While preliminary, these data bolster our belief that RMC-9805 has the potential to play a role in an emerging treatment paradigm for patients living with pancreatic cancer, both as monotherapy and in combinations. With today’s presentation, RMC-9805 becomes the third tri-complex compound from the Revolution Medicines pipeline to demonstrate clinical proof-of-concept, and it reaffirms our commitment to bringing novel RAS(ON) inhibitors to patients with RAS-addicted cancers.”
The RMC-9805-001 Phase 1/1b study is a multicenter, open-label, dose-escalation and dose-expansion study designed to evaluate RMC-9805 in patients with advanced solid tumors harboring a KRAS G12D mutation. As of the September 2, 2024 data cutoff date, 179 patients were treated with escalating doses of RMC-9805 (ranging from 150-1200 mg once daily (QD) and 300-600 mg twice daily (BID)). Study patients had received a median of two prior therapies (range 0-9) and all had previously been treated with standard of care.
As of the data cutoff date, RMC-9805 demonstrated an encouraging safety profile and was generally well tolerated across dose levels. For patients receiving 1200 mg of RMC-9805 daily (n = 99), the most common treatment-related adverse events (TRAEs) occurring in greater than
Preliminary efficacy was assessed in PDAC patients. At a candidate recommended Phase 2 dose of 1200 mg daily (20 patients at 1200 mg QD and 20 patients at 600 mg BID), patients who received a first dose of RMC-9805 at least 14 weeks prior to the data cutoff date achieved a
“Pancreatic cancer is the most RAS-addicted of all major cancers and the G12D variant is the most common RAS mutation in pancreatic cancer. No approved targeted therapies are available for these patients, making this an area of significant unmet need,” said David Hong, M.D. of MD Anderson Cancer Center, principal investigator and lead author for the RMC-9805-001 presentation. “This is a challenging disease, but we observed a promising level of antitumor activity at generally tolerable doses in this Phase 1 study."
Investor Webcast
Revolution Medicines will host an investor webcast on Friday, October 25, 2024 at 12:00 p.m. Eastern Time / 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 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; the company’s belief that RMC-9805 could play a role in treatment options for pancreatic cancer patients; the company’s beliefs regarding demonstration of clinical proof-of-concept; and the company’s plans to bring RAS(ON) inhibitors to 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
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