Revolution Medicines Presents Initial Data from Zoldonrasib (RMC-9805) Study in Patients with KRAS G12D Mutant Non-Small Cell Lung Cancer at the 2025 AACR Annual Meeting

Rhea-AI Summary

Revolution Medicines (RVMD) has presented initial clinical data for zoldonrasib (RMC-9805), their RAS(ON) G12D-selective inhibitor, in treating KRAS G12D mutant non-small cell lung cancer (NSCLC) patients. The Phase 1 study results were presented at the 2025 AACR Annual Meeting.

Key findings from the study with 90 solid tumor patients treated with 1200 mg once daily dose showed:

• 61% objective response rate in 18 efficacy-evaluable NSCLC patients
• 89% disease control rate
• 98% mean dose intensity with no dose limiting toxicities
• Acceptable safety profile with mostly Grade 1 or 2 adverse events

Common treatment-related adverse events included nausea (39%), diarrhea (24%), vomiting (18%), and rash (12%). Only 2% of patients experienced Grade 3 events, which resolved after dose interruption.

Positive

• High objective response rate of 61% in NSCLC patients
• Strong disease control rate of 89%
• Favorable safety profile with 98% mean dose intensity
• Only 2% of patients experienced Grade 3 adverse events, which were reversible

Negative

• Small sample size of only 18 efficacy-evaluable NSCLC patients
• Study still in early Phase 1 stage

Insights

Oncology Expert

Revolution Medicines' zoldonrasib shows promising 61% response rate in KRAS G12D lung cancer with good tolerability, addressing significant unmet need.

The initial clinical data for zoldonrasib (RMC-9805) represents a potentially significant advancement in treating KRAS G12D mutant non-small cell lung cancer, an area with no currently approved targeted therapies. The reported 61% objective response rate and 89% disease control rate in 18 efficacy-evaluable NSCLC patients are particularly encouraging for a targeted therapy in previously treated patients.

The safety profile appears manageable, with primarily Grade 1-2 adverse events including nausea (39%), diarrhea (24%), vomiting (18%), and rash (12%). Only 2% of patients experienced Grade 3 events that resolved after dose interruption. The 98% mean dose intensity without dose-limiting toxicities suggests patients can maintain treatment consistently—a critical factor for clinical benefit in advanced cancer settings.

KRAS mutations have historically been considered "undruggable" until recent breakthroughs. The G12D variant specifically represents a substantial subset of KRAS-mutated cancers with treatment options. These preliminary results suggest zoldonrasib may offer a viable targeted approach for this patient population.

While these data are promising, they come from a small patient subset in an early-phase trial. The consistent efficacy signals across both NSCLC and previously reported pancreatic cancer patients indicate potential utility across multiple KRAS G12D-driven tumor types, which could expand the therapeutic impact of this compound.

Biotechnology Analyst

Revolution Medicines' zoldonrasib shows strong early efficacy data in lung cancer, advancing their targeted RAS inhibitor pipeline with blockbuster potential.

Revolution Medicines' development of zoldonrasib, their RAS(ON) G12D-selective inhibitor, represents a strategic advance in their focused pipeline targeting RAS-addicted cancers. The Phase 1 data presented at AACR 2025 demonstrates the company's progress in addressing one of oncology's most challenging targets.

The clinical development appears to be progressing efficiently, with the company having already identified 1200 mg once daily as the candidate recommended Phase 2 dose based on data from 90 solid tumor patients. The established safety profile aligns with previous pancreatic cancer data, suggesting a consistent and predictable tolerability pattern across tumor types—an important consideration for potential combination strategies mentioned in the release.

The 61% objective response rate in NSCLC is particularly noteworthy as it demonstrates the compound's activity beyond pancreatic cancer, potentially broadening its market opportunity across multiple tumor types harboring the KRAS G12D mutation. This mutation type represents an area of significant unmet need explicitly acknowledged by the trial investigator.

From a pipeline perspective, these results strengthen Revolution Medicines' position in the competitive RAS inhibitor landscape. The company appears to be executing well on its clinical strategy of establishing monotherapy efficacy before exploring combination approaches. The presentation of these results at a major scientific conference (AACR) and inclusion in the official press program indicates recognition of the data's significance within the oncology community, potentially enhancing the company's scientific credibility and visibility to partners and investors.

Zoldonrasib, a RAS(ON) G12D-selective inhibitor, demonstrated acceptable tolerability and encouraging initial antitumor activity in patients with previously treated KRAS G12D mutant non-small cell lung cancer

REDWOOD CITY, Calif., April 27, 2025 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, today announced new clinical data for zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, as monotherapy in patients with KRAS G12D mutant non-small cell lung cancer (NSCLC). Results were highlighted in the official press program at the American Association for Cancer Research (AACR) Annual Meeting in Chicago, Illinois, and will be featured in a late-breaking oral presentation on April 27, 2025, at 5:00 p.m. Central Time.

“We are pleased to share new clinical data for zoldonrasib, our innovative, oral RAS(ON) G12D-selective inhibitor, which demonstrates acceptable safety and tolerability and encouraging initial antitumor activity in patients with non-small cell lung cancer. These data reinforce the clinical potential of zoldonrasib following the initial tolerability and antitumor activity reported late last year in patients with pancreatic ductal adenocarcinoma,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “Together these results support further evaluation of zoldonrasib as monotherapy and in combination as we continue efforts to advance innovative targeted medicines for patients living with these hard-to-treat cancers.”

RMC-9805-001 is a multicenter, open-label, dose escalation and dose-expansion Phase 1 study designed to evaluate zoldonrasib in patients with advanced solid tumors harboring a KRAS G12D mutation.

As of a December 2, 2024 data cutoff date, 90 solid tumor patients were treated with 1200 mg once daily (QD), the candidate recommended Phase 2 dose. In these patients, zoldonrasib demonstrated an acceptable safety profile, that was generally consistent with previously reported data for this compound in pancreatic cancer, and was generally well tolerated. The most common treatment-related adverse events (TRAEs) occurring in at least 10% of patients were nausea (39%), diarrhea (24%), vomiting (18%), and rash (12%). TRAEs were primarily Grade 1 or 2 in severity, with two patients (2%) experiencing Grade 3 events that resolved following dose interruption. Zoldonrasib had a favorable mean dose intensity of 98% and no dose limiting toxicities were observed.

Preliminary antitumor activity was assessed in 18 efficacy-evaluable patients with NSCLC at the 1200 mg QD dose. The objective response rate (confirmed or pending confirmation) was 61% (n=11) and the disease control rate was 89% (n=16).

“There is a high unmet need for new treatments within this patient population as there are currently no targeted therapies approved for any RAS G12D mutant cancer,” said Kathryn Arbour, M.D., thoracic medical oncologist at Memorial Sloan Kettering Cancer Center and principal investigator and lead author for the RMC-9805-001 presentation. “While the data are from an early, small subset of patients, it is encouraging to see this level of tolerability and antitumor activity in patients with NSCLC carrying this RAS mutation.”

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; and zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, are currently in clinical development. The company anticipates that RMC-5127, a RAS(ON) G12V-selective inhibitor, will be its next RAS(ON) inhibitor to enter 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; and the potential of zoldonrasib as a therapeutic option for pancreatic ductal adenocarcinoma or non small cell lung cancer. 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’ Annual Report on Form 10-K filed with the Securities and Exchange Commission (the “SEC”) on February 26, 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 

FAQ

What are the initial results of Revolution Medicines' zoldonrasib (RVMD) in NSCLC patients?

Zoldonrasib showed a 61% objective response rate and 89% disease control rate in NSCLC patients with KRAS G12D mutations, with acceptable safety profile at 1200mg daily dose.

What are the main side effects reported for zoldonrasib (RVMD) in the Phase 1 trial?

Main side effects included nausea (39%), diarrhea (24%), vomiting (18%), and rash (12%), mostly Grade 1 or 2 in severity.

How many patients were evaluated in the RVMD zoldonrasib NSCLC trial?

90 solid tumor patients received treatment, with efficacy evaluated in 18 NSCLC patients at the 1200 mg daily dose.

What is the significance of zoldonrasib's results for KRAS G12D mutant cancer treatment?

These results are significant as there are currently no approved targeted therapies for any RAS G12D mutant cancers, representing an unmet medical need.