01—Abstract
Summary
Summary of the 8-K filed October 23, 2024. Cited figures are marked; the original filing is the authoritative source.
On October 23, 2024, Revolution Medicines, Inc. disclosed updated clinical data for RMC-6236, its RAS(ON) multi-selective inhibitor, from the monotherapy first-in-human Phase 1 RMC-6236-001 study, with a data cutoff of July 23, 2024, in patients with previously treated pancreatic ductal adenocarcinoma (PDAC).
Across 127 patients treated at doses from 160 mg to 300 mg daily, 98%a experienced a treatment-related adverse event (TRAE), 29% at Grade 3 or higher. The most common TRAEs were rash (91%, with 8% at Grade 3 or higher) and gastrointestinal effects such as diarrhea (48%) and nausea (43%). One Grade 4 TRAE (platelet count decreased) and no Grade 5 TRAEs were observed, and no TRAEs led to treatment discontinuation, though 35% led to dose modifications.
Preliminary efficacy data in metastatic PDAC showed median progression-free survival of 8.5 months in second-line patients with KRAS G12X mutations (95%b CI: 5.3–11.7 months) and 4.4 months in third-line or later patients with the same mutation (95% CI: 4.2–6.4 months). In second-line patients, median overall survival was 14.5 months for both KRAS G12X and G12/G13/Q61 tumors, with a 6-month OS rate of 89% and 91%, respectively. For patients first dosed at least 14 weeks before the cutoff, objective response rate was 29% in second-line and 22% in third-line or later patients, and disease control rate was 91% and 89%.
The filing is a pipeline update under Item 8.01 and references the company's Form 10-Q filed August 7, 2024, for risk factors. The data are preliminary and drawn from a single-arm Phase 1 study, and the filing includes forward-looking statements about the drug's potential safety, tolerability, efficacy and durability.
02—Key points
Key Highlights
- 127 patients with previously treated PDAC received RMC-6236 at 160 mg to 300 mg daily as of the July 23, 2024 data cutoff.
- Rash (91%) and gastrointestinal toxicities, including diarrhea (48%) and nausea (43%), were the most common TRAEs; 29% of patients had Grade 3 or higher TRAEs.
- One Grade 4 TRAE (platelet count decreased) and no Grade 5 TRAEs were observed; no TRAEs led to discontinuation.
- Median PFS in second-line PDAC with KRAS G12X mutations was 8.5 months (95% CI: 5.3–11.7); in third-line or later it was 4.4 months (95% CI: 4.2–6.4).
- Interim median OS in second-line PDAC was 14.5 months for both KRAS G12X and G12/G13/Q61 tumors; 6-month OS rate was 89% and 91%, respectively.
- Objective response rate was 29% in second-line and 22% in third-line or later patients (first dose at least 14 weeks before cutoff); disease control rate was 91% and 89%.
03—Questions
Frequently Asked Questions
What did Revolution Medicines report about RMC-6236 in this filing?
The company reported updated safety, tolerability and preliminary efficacy data from its Phase 1 RMC-6236-001 monotherapy study in patients with previously treated pancreatic ductal adenocarcinoma, with a data cutoff of July 23, 2024.
What were the main safety findings?
Rash and gastrointestinal toxicities were most common. Any-grade TRAEs occurred in 98% of 127 patients, and Grade 3 or higher TRAEs in 29%. One Grade 4 event (platelet count decreased) was seen, with no Grade 5 events and no treatment discontinuations due to TRAEs. Dose modifications occurred in 35% of patients.
How did patients fare in terms of survival and progression?
In second-line patients with KRAS G12X mutations, median PFS was 8.5 months and median OS was 14.5 months. In third-line or later patients with KRAS G12X mutations, median PFS was 4.4 months. The OS data are interim and the OS upper confidence bound was not estimable.
What response rates were observed?
Among patients first dosed at least 14 weeks before the cutoff, objective response rate was 29% in the second-line setting and 22% in the third-line or later setting, with disease control rates of 91% and 89%, respectively.
What limitations should investors consider?
The data are preliminary, come from a single-arm Phase 1 study with small subgroups, and are subject to the confidence intervals reported. The filing notes that results from prior trials may not predict future outcomes and points to the company's Form 10-Q filed August 7, 2024 for risk factors.
04—Continue