Investigational Drug
Zoldonrasib
TrialFetch AI Analysis
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Overview
Zoldonrasib (RM-036; RMC-9805) is an investigational oral drug for cancers with a KRAS G12D mutation. Human results have been reported, but they remain preliminary: the studies summarized below are early-phase and do not establish whether zoldonrasib improves survival compared with standard treatment. (aacrjournals.org)
Mechanism of action
Zoldonrasib forms a complex with cyclophilin A that binds irreversibly to the active, GTP-bound form of KRAS G12D, blocking downstream growth signaling. (cancer.gov)
Efficacy
- Previously treated non-small cell lung cancer: In a phase 1 study, 14 of 27 selected patients (52%) had a confirmed objective response to zoldonrasib alone; 93% had a response or stable disease. (aacrjournals.org)
- Metastatic pancreatic cancer: In separate early-phase studies, objective response rates were 50% in 30 second-line patients and 47% in 30 later-line patients receiving zoldonrasib plus daraxonrasib. With first-line chemotherapy, response rates were 82% in 22 evaluable patients receiving modified FOLFIRINOX and 61% in 31 receiving gemcitabine/nab-paclitaxel. These combination results cannot isolate zoldonrasib’s contribution. (annalsofoncology.org)
Safety
Among 40 lung-cancer patients receiving zoldonrasib alone, common treatment-related adverse events were nausea (43%), vomiting (33%), diarrhea (30%), and rash (18%); 13% had grade 3 events, with no grade 4 or 5 treatment-related events reported. In the pancreatic-cancer combination studies, grade 3 or higher treatment-related events occurred in 35% with daraxonrasib and 61%–80% with chemotherapy; the daraxonrasib combination study reported one treatment-related death from intestinal perforation. (aacrjournals.org)
Further reading
- NCI Drug Dictionary: zoldonrasib
- AACR 2026 lung-cancer trial abstract
- Pancreatic-cancer combination abstracts: daraxonrasib and chemotherapy
Last updated: Sep 2026
Active trials using Zoldonrasib
Found 4 active trials using this drug:
TrialFetch AI summary: Adults with previously untreated metastatic KRAS G12D-mutated pancreatic adenocarcinoma and ECOG performance status 0–1 are randomized to oral daraxonrasib plus zoldonrasib or gemcitabine plus nab-paclitaxel. Daraxonrasib inhibits active RAS broadly, while zoldonrasib selectively inhibits active KRAS G12D.
ClinicalTrials.gov ID: NCT07805954
TrialFetch AI summary: Adults with previously untreated metastatic nonsquamous NSCLC harboring a RAS G12D mutation receive first-line pembrolizumab, pemetrexed, and cisplatin or carboplatin plus either zoldonrasib or placebo. Zoldonrasib is an investigational inhibitor of active KRAS G12D that suppresses downstream RAS signaling.
ClinicalTrials.gov ID: NCT07777822
TrialFetch AI summary: Adults with previously untreated metastatic KRAS G12D-mutated pancreatic adenocarcinoma and ECOG 0–1 receive investigator-selected modified FOLFIRINOX or gemcitabine plus nab-paclitaxel, with either oral zoldonrasib or placebo. Zoldonrasib is an investigational inhibitor of active KRAS G12D that forms a complex with cyclophilin A to block downstream signaling.
ClinicalTrials.gov ID: NCT07621718
TrialFetch AI summary: Adults with ECOG 0–1 and advanced or metastatic RAS-mutant solid tumors are eligible; expansion cohorts include untreated nonsquamous NSCLC and previously treated solid tumors or colorectal cancer. Treatment pairs ivonescimab (PD-1/VEGF-A bispecific antibody) with a RAS(ON) inhibitor—daraxonrasib (multiple RAS variants), elironrasib (KRAS G12C), or zoldonrasib (KRAS G12D)—with selected cohorts adding platinum–pemetrexed, daraxonrasib, or cetuximab.
ClinicalTrials.gov ID: NCT07397338
