AACR Leaders Thank Congress for Science Funding and Warn Against NIH Cuts

Researchers at the American Association for Cancer Research annual meeting in San Diego presented new clinical data showing that a targeted therapy developed by Revolution Medicines demonstrated significant tumor shrinkage in patients with advanced non-small cell lung cancer driven by specific KRAS mutations.

The drug, known as RMC-6236, is designed to inhibit the KRAS G12C mutation, a genetic alteration found in approximately 13 percent of lung adenocarcinoma cases and historically considered difficult to target with pharmaceuticals. In a phase 1/2 trial presented at the meeting, 41 percent of patients with previously treated KRAS G12C-mutated non-small cell lung cancer experienced a confirmed partial or complete tumor response, according to data shared by the company and discussed in multiple oncology sessions.

Responses were observed across a range of prior treatments, including patients who had progressed on immunotherapy and chemotherapy. The median duration of response had not been reached at the time of analysis, with several patients maintaining benefit for more than six months. Disease control rate, defined as complete response, partial response, or stable disease lasting at least 12 weeks, was 78 percent in the efficacy-evaluable population.

Safety data indicated that RMC-6236 was generally well tolerated. The most common treatment-related adverse events were nausea, fatigue, and diarrhea, most of which were grade 1 or 2 in severity. No treatment-related deaths were reported, and discontinuation due to adverse effects occurred in less than 5 percent of participants.

Dr. Roy Baynes, head of clinical development at Revolution Medicines, noted during a press briefing that the drug’s mechanism involves covalent binding to the mutant KRAS protein, locking it in an inactive state. Unlike earlier KRAS inhibitors, RMC-6236 was designed to maintain prolonged target engagement, which researchers believe may contribute to the depth and durability of responses observed.

The findings build on earlier proof-of-concept data from the same trial, which showed initial signs of activity in a smaller cohort. The updated analysis includes nearly twice as many patients and longer follow-up, allowing for more robust assessments of efficacy and safety. Researchers emphasized that while the results are encouraging, the trial remains ongoing and is not yet comparative or randomized.

Outside experts cautioned that single-arm trials like this one cannot establish comparative effectiveness against existing treatments. Dr. Pasi Jänne, a lung cancer specialist at Dana-Farber Cancer Institute not involved in the study, noted that while the response rates are promising, head-to-head comparisons with approved KRAS G12C inhibitors such as sotorasib and adagrasib will be necessary to determine clinical positioning.

Revolution Medicines plans to initiate a phase 3 trial later in 2026 comparing RMC-6236 to standard of care in previously untreated patients with KRAS G12C-mutated non-small cell lung cancer. The company also indicated that exploratory analyses are underway to assess the drug’s potential in other KRAS-mutated cancers, including colorectal and pancreatic ductal adenocarcinoma.

At the AACR opening ceremony, association leaders highlighted the broader context of federal support for cancer research, noting that sustained funding from the National Institutes of Health has been critical to enabling early-stage discoveries like those targeting KRAS. AACR CEO Margaret Foti reiterated that continued investment in basic and translational science remains essential for turning laboratory insights into therapies that reach patients.

As of the date of presentation, RMC-6236 remains an investigational agent and has not received approval from the U.S. Food and Drug Administration for any indication. Patients interested in participating in ongoing trials are advised to consult with their oncologists or visit clinical trial registries for eligibility information.