Investigational Drug
RMC-9805
TrialFetch AI Analysis
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Overview
RMC-9805 (zoldonrasib) is an investigational oral drug being studied for advanced cancers with a KRAS G12D mutation. Human results are available from an ongoing phase 1 study, but they remain preliminary and come from relatively small, non-randomized groups. (aacrjournals.org)
Mechanism of action
RMC-9805 targets the active, GTP-bound form of RAS G12D. It forms a three-part complex with RAS and the cellular protein cyclophilin A, covalently engaging the mutant protein and disrupting downstream signaling. (aacrjournals.org)
Efficacy
- Non-small cell lung cancer: In a 2026 conference abstract, 14 of 27 previously treated patients receiving 1,200 mg once daily had a confirmed response (52%); 93% had disease control. Median progression-free survival was 11.1 months. (aacrjournals.org)
- Pancreatic ductal adenocarcinoma: An earlier phase 1 abstract reported a 30% response rate and 80% disease-control rate among 40 patients receiving a total of 1,200 mg daily. That response figure included responses pending confirmation, so it should not be treated as directly comparable with the confirmed lung-cancer figure. (asco.org)
Safety
In the 2026 lung-cancer analysis of 40 patients, the most common treatment-related adverse events were nausea (43%), vomiting (33%), diarrhea (30%) and rash (18%). Grade 3 treatment-related events occurred in 13%; none were grade 4 or 5. Treatment-related events led to discontinuation in 5%. Longer-term safety remains to be established. (aacrjournals.org)
Further reading
- 2026 AACR lung-cancer clinical abstract
- 2025 ASCO pancreatic-cancer clinical abstract
- 2024 AACR drug-discovery abstract
Last updated: Sep 2026
Active trials using RMC-9805
Found 4 active trials using this drug:
TrialFetch AI summary: Adults with previously treated advanced pancreatic ductal adenocarcinoma or NSCLC harboring MTAP loss and a RAS mutation receive oral vopimetostat (TNG462), an MTAP-selective PRMT5 inhibitor, plus either daraxonrasib (RMC-6236), a multi-variant RAS inhibitor, or zoldonrasib (RMC-9805), a KRAS G12D inhibitor. Prior RAS-targeted therapy, PRMT5 inhibitors, or MAT2A inhibitors are excluded.
ClinicalTrials.gov ID: NCT06922591
TrialFetch AI summary: Adults with unresectable or metastatic colorectal cancer or metastatic pancreatic ductal adenocarcinoma receive oral RMC-6236, a multiselective active-RAS inhibitor, combined with fluorouracil-based chemotherapy and bevacizumab, cetuximab with or without mFOLFOX6, or gemcitabine plus nab-paclitaxel. In RAS G12D-mutant cohorts, the active-RAS G12D inhibitor RMC-9805 is given with or without RMC-6236 alongside the corresponding regimens.
ClinicalTrials.gov ID: NCT06445062
TrialFetch AI summary: This study enrolls previously treated adults with locally advanced or metastatic RAS-mutated NSCLC, with additional cohorts for KRAS G12C-mutated solid tumors and KRAS G12D-mutated NSCLC. It evaluates active RAS inhibitors—KRAS G12C–targeted RMC-6291, multi-variant RAS–targeted RMC-6236, and KRAS G12D–targeted RMC-9805—in mutation-specific combinations with pembrolizumab, with or without platinum/pemetrexed chemotherapy.
ClinicalTrials.gov ID: NCT06162221
TrialFetch AI summary: Adults with locally advanced or metastatic KRAS G12D-mutant solid tumors after progression on or intolerance to standard therapy receive oral zoldonrasib (RMC-9805), an active KRAS G12D inhibitor, alone or with daraxonrasib (RMC-6236), an active pan-RAS inhibitor. Both drugs form cyclophilin A–mediated complexes to disrupt RAS signaling.
ClinicalTrials.gov ID: NCT06040541
