Investor Webcast to be held Sunday, October 22 at 12:30 p.m. Eastern Time

REDWOOD CITY, CA, USA I October 22, 2023 I Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, today announced promising anti-tumor and safety data for RMC-6236, its RASMULTI(ON) Inhibitor, in patients with previously treated non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) across several dose levels and KRASG12X genotypes, including common KRAS-mutant genotypes G12D and G12V. These initial results were presented during a Proffered Paper session at the European Society for Medical Oncology (ESMO) Congress in Madrid, October 20-24, 2023.

“Today’s presentation marks an important milestone in the clinical development of RMC-6236, an unprecedented, oral RASMULTI(ON) Inhibitor with an innovative mechanism of action. The findings reinforce our belief that by inhibiting the (ON), or active, form of diverse RAS cancer drivers, RMC-6236 can lead to meaningful clinical responses in patients at dose levels that are generally well tolerated,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “These data also confirm that RMC-6236 can target multiple common RAS variants that cause cancer, supporting its ongoing development as monotherapy in patients with NSCLC or PDAC harboring RAS mutations. Further, RMC-6236 has a compelling profile for evaluation in combination treatment strategies with RMC-6291, our mutant-selective RASG12C(ON) Inhibitor, and with immunotherapy and other cancer drugs.”

The RMC-6236-001 Phase 1/1b trial 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 KRASG12X mutations. As of an October 12, 2023 data extraction, a total of 111 patients with NSCLC (n=46) or PDAC (n=65) were treated at dose levels administered once daily (QD) ranging from 80 mg to 400 mg. Common KRAS mutations in patients evaluated included G12D, G12V, G12R, G12A and G12S; patients with KRASG12C mutations were excluded from the study due to the availability of currently approved KRASG12C(OFF) inhibitors. All patients had previously been treated with standard of care appropriate for tumor type and stage. Patients with NSCLC had received a median of two prior lines of therapy (range 1–6) while patients with PDAC had received a median of three prior lines of therapy (range 1–7).

RMC-6236 demonstrated preliminary evidence of clinical activity and an acceptable safety profile that was generally well tolerated across the dose levels analyzed. Clinical activity was evaluated in patients who had received the first dose of RMC-6236 at least eight weeks prior to the data extraction date (n=86). Among the 40 efficacy evaluable NSCLC patients, the objective response rate was 38 percent, with one patient achieving a complete response (CR) as a best response and 14 patients achieving a partial response (PR) (including three unconfirmed PRs). The disease control rate (DCR) in this NSCLC population was 85 percent. Among the 46 efficacy evaluable PDAC patients, the objective response rate was 20 percent, with nine patients achieving a PR (including four unconfirmed PRs) as a best response. The DCR in this PDAC population was 87 percent. Confirmed objective responses included tumors harboring KRAS mutations G12D, G12V or G12R, and disease control was observed across all KRAS mutations, including G12A and G12S.

The most common treatment-related adverse events (TRAEs) were rash and GI-related toxicities that were primarily Grade 1 or 2 in severity. The reported Grade 3 TRAEs were rash (6%), stomatitis (2%), and diarrhea (1%). One previously reported Grade 4 TRAE occurred in a patient with PDAC at the 80 mg QD dose level who had a large intestine perforation at the site of an invasive tumor that reduced in size while on treatment, which resulted in treatment discontinuation. No safety signals were observed that indicated an elevated risk of hepatotoxicity, which has been reported for some KRASG12C(OFF) inhibitors.

“There is a high unmet need among patients living with KRAS-mutated NSCLC or PDAC, two aggressive cancer types for which current standard of care treatments are often inadequate,” said Kathryn C. Arbour, M.D., thoracic oncologist at Memorial Sloan Kettering Cancer Center and a principal investigator for the RMC-6236-001 study. “It is quite encouraging to see this level of anti-tumor activity in previously treated patients by a generally well-tolerated investigational drug. We look forward to continuing the dose optimization portion of the Phase 1/1b study to inform future development and further our understanding of the effects of RMC-6236 on RAS-mutant cancers.”

Investor Webcast
Revolution Medicines will host an investor webcast on Sunday, October 22, 2023 at 12:30 p.m. Eastern Time to discuss the data presented at both the 2023 AACR-NCI-EORTC Triple meeting and ESMO, in addition to other pipeline updates. To participate in the live webcast, participants may register in advance here: A live webcast of the call will also be available on the Investors section of Revolution Medicines’ website at Following the live webcast, a replay will be available on the company’s website for at least 14 days.

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, and RAS Companion Inhibitors for use in combination treatment strategies. The company’s RAS(ON) Inhibitors RMC-6236 (RASMULTI), RMC-6291 (KRASG12C) and RMC-9805 (KRASG12D) are currently in clinical development. Additional RAS(ON) Inhibitors in the company’s pipeline include RMC-0708 (KRASQ61H) and RMC-5127 (KRASG12V) which are currently in IND-enabling development, RMC-8839 (KRASG13C), and additional compounds targeting other RAS variants. RAS Companion Inhibitors in clinical development include RMC-4630 (SHP2) and RMC-5552 (mTORC1/4EBP1).

SOURCE: Revolution Medicines