Revolution Medicines Doses First Patient in Clinical Trial Evaluating RMC-5127, a RAS(ON) G12V-Selective Inhibitor
Rhea-AI Summary
Revolution Medicines (NASDAQ:RVMD) announced dosing of the first patient in the first-in-human trial RMC-5127-001 (NCT07349537), evaluating RMC-5127, a RAS(ON) G12V-selective inhibitor.
The open-label trial will assess safety, tolerability, pharmacokinetics and preliminary antitumor activity as monotherapy and in combination in patients with RAS G12V–mutated PDAC, CRC and NSCLC. RMC-5127 is the company’s fifth disclosed mutant-selective RAS(ON) inhibitor and fourth clinical-stage program, targeting an estimated ~48,000 U.S. patients diagnosed annually with RAS G12V–driven cancers.
Positive
- First patient dosed in first-in-human trial RMC-5127-001 (NCT07349537)
- RMC-5127 targets the RAS G12V variant, affecting ~48,000 U.S. patients annually
- Program is the company’s fifth mutant-selective RAS(ON) inhibitor and fourth clinical-stage program
- Trial includes both monotherapy and combination cohorts to evaluate safety, PK, and antitumor activity
Negative
- First-in-human, open-label trial means safety and efficacy are unproven at this stage
News Market Reaction – RVMD
In the Jan 29 session, RVMD gained 0.89%, reflecting a mild positive market reaction.
Data tracked by StockTitan Argus on the day of publication.
Key Figures
Previous Clinical trial Reports
| Date | Event | Sentiment | 24h Move | Catalyst |
|---|---|---|---|---|
| Dec 18 | Phase 3 PDAC trial | Positive | -1.0% | First patient randomized in global Phase 3 RASolute 304 trial of daraxonrasib. |
| Oct 27 | Orphan designation | Positive | +6.4% | FDA Orphan Drug Designation for daraxonrasib in pancreatic cancer. |
| Sep 10 | Positive PDAC data | Positive | +14.3% | Promising daraxonrasib efficacy data supporting RASolute 303 Phase 3 initiation. |
| May 14 | NSCLC Phase 3 start | Positive | -1.2% | First patient dosed in Phase 3 RASolve 301 daraxonrasib NSCLC study. |
| Oct 21 | PDAC Phase 3 start | Positive | -1.3% | First patient dosed in Phase 3 RASolute 302 trial of RMC-6236 in PDAC. |
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Clinical trial headlines have produced mixed reactions: some Phase 3 and designation updates drew strong gains, while several “first patient” milestones saw mild declines.
Over the past year, RVMD has repeatedly advanced its RAS(ON) pipeline with multiple Phase 3 programs in PDAC and NSCLC and first-patient dosing milestones. Prior clinical trial news, such as initiation of RASolute 302 and RASolve 301, often focused on large patient populations and survival endpoints. Same-tag events showed an average move of about 4.85%, with both positive spikes and modest selloffs. Today’s first-in-human RMC-5127 update extends this pattern of pipeline broadening in RAS-driven cancers.
Key Terms
ras(on) medical
g12v medical
pharmacokinetics medical
pancreatic ductal adenocarcinoma medical
non–small cell lung cancer medical
oncogenic medical
cyclophilin a medical
monotherapy medical
AI-generated analysis. How Rhea-AI works. Not financial advice.
REDWOOD CITY, Calif., Jan. 29, 2026 (GLOBE NEWSWIRE) -- Revolution Medicines, a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, today announced the first patient was dosed in its first-in-human clinical trial evaluating RMC-5127, a RAS(ON) G12V-selective inhibitor.
The first-in-human trial, RMC-5127-001 [NCT07349537], is an open-label trial evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of RMC-5127 as both a monotherapy and in combination settings. The trial will enroll patients with RAS G12V–mutated solid tumors, including pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and non–small cell lung cancer (NSCLC), who have progressed on or are intolerant to prior standard therapies, including targeted treatments.
“By bringing RMC-5127 to the clinic, we are building on our well-validated RAS(ON) inhibitor approach and extending it to RAS G12V, the second most common RAS mutation driving human cancers, where there are no approved targeted treatment options,” said Alan Sandler, M.D., chief development officer of Revolution Medicines. “As our fifth disclosed mutant-selective RAS(ON) inhibitor and fourth clinical-stage program, RMC-5127 broadens the RAS variant coverage of our growing portfolio and opens a suite of development opportunities aimed at improving outcomes for patients with RAS-driven cancers.”
RMC-5127 is an innovative inhibitor that binds to cyclophilin A, creating a complex that selectively recognizes and inhibits the oncogenic RAS(ON) form of the RAS G12V variant. RAS G12V is the second most common driver of RAS-addicted human cancers with approximately 48,000 patients diagnosed in the U.S.1 each year, predominantly among patients with PDAC, CRC, or NSCLC.
About Revolution Medicines, Inc.
Revolution Medicines is a late-stage clinical oncology company developing novel targeted therapies for patients with 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 daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), a RAS(ON) G12C-selective inhibitor; zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor; and RMC-5127, a RAS(ON) G12V-selective inhibitor, are currently in clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-0708 (Q61H) and RMC-8839 (G13C). For more information, please visit www.revmed.com and follow us on LinkedIn.
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 potential impact of RMC-5127 for patients with KRAS G12V mutations; and the ability of the company to transform outcomes for patients with RAS-driven cancers. 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 November 5, 2025, 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.
Revolution Medicines Media & Investor Contact:
media@revmed.com
investors@revmed.com
1 Estimated using tumor mutation frequencies from Foundation Medicine Insights March 2022 and scaled to estimated patient numbers using cancer incidence from ACS Cancer Facts and Figures 2023
