01—Abstract
Summary
Summary of the 8-K filed October 25, 2024. Cited figures are marked; the original filing is the authoritative source.
On October 25, 2024, Revolution Medicines, Inc. reported preliminary clinical safety, tolerability and activity data for RMC-9805, its RAS(ON) oral tri-complex G12D-selective inhibitor, from its monotherapy first-in-human study (RMC-9805-001), with a data cutoff date of September 2, 2024, in patients with previously treated solid tumors harboring KRAS G12D mutations.
Across 179 treated patients (doses from 150 mg to 1,200 mg once daily and 300 mg to 600 mg twice daily), the most common treatment-related adverse events were gastrointestinal, led by nausea (30%a any grade) and diarrhea (16%). TRAEs led to dose reduction in approximately 3% of patients, no TRAEs led to treatment discontinuation, and no treatment-related Grade 4 or 5 adverse events or serious adverse events were reported. Median time on treatment was 2.8 months.
In the 99 patients who received 1,200 mg per day, the most common TRAEs were again gastrointestinal-related plus rash, with dose reductions in approximately 4%b and no discontinuations. For 20 second-line-or-later pancreatic ductal adenocarcinoma patients treated at 1,200 mg per day who received a first dose at least 14 weeks before the cutoff, the objective response rate (including confirmed and pending responses) was 30% and the disease control rate was 80%. The company states these preliminary data support continued development of RMC-9805 as a single agent and in combination with other therapies, including its RAS(ON) multi-selective inhibitor RMC-6236.
02—Key points
Key Highlights
- RMC-9805-001 study enrolled and evaluated 179 patients with previously treated solid tumors harboring KRAS G12D mutations as of the September 2, 2024 data cutoff.
- Most common treatment-related adverse events were gastrointestinal: nausea (30% any grade), diarrhea (16%) and vomiting (15%).
- TRAEs led to dose reduction in approximately 3% of patients; no TRAEs led to treatment discontinuation.
- No treatment-related Grade 4 or 5 adverse events or serious adverse events were reported.
- In 99 patients receiving 1,200 mg per day, TRAEs led to dose reduction in approximately 4% and no treatment discontinuations occurred.
- In 2L+ PDAC patients treated at 1,200 mg per day (n=40 total cohort with 20 per dosing arm), objective response rate was 30% and disease control rate was 80%.
- Company believes the data support development of RMC-9805 alone and in combination with RMC-6236.
03—Questions
Frequently Asked Questions
What is RMC-9805 and what does it target?
RMC-9805 is Revolution Medicines' RAS(ON) oral tri-complex G12D-selective inhibitor, being studied in a monotherapy first-in-human study in patients with previously treated solid tumors harboring KRAS G12D mutations.
What were the main safety findings?
The most common treatment-related adverse events were gastrointestinal, including nausea (30% any grade), diarrhea (16%) and vomiting (15%). Rash and ALT elevation were also reported in a smaller share of patients. No treatment-related Grade 4 or 5 events or serious adverse events were reported.
How many patients were treated and for how long?
A total of 179 patients were treated across dose cohorts as of the September 2, 2024 data cutoff. The median time on treatment was 2.8 months, with a range of 0.1 to 8.9 months.
What efficacy signals were reported?
In second-line-or-later pancreatic ductal adenocarcinoma patients receiving 1,200 mg per day who had a first dose at least 14 weeks before the cutoff, the objective response rate, including confirmed and pending responses, was 30% and the disease control rate was 80%. Among patients with a response, 55% had their first response after 2 months of treatment.
What are the next steps for RMC-9805?
The company believes the preliminary data support its ongoing development of RMC-9805 as a single agent and in combination with other therapies, including RMC-6236, its RAS(ON) multi-selective inhibitor.
04—Continue