Drug intelligence / Profile preview

zoldonrasib + gemcitabine + nab-paclitaxel

Development stage
Phase 3
Lead developer
REVOLUTION Medicines
Modality
Small Molecules
Administration
Intravenous, Oral
01

Overview

Zoldonrasib + gemcitabine + nab-paclitaxel is an investigational combination regimen being evaluated for the first-line treatment of patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC) harboring a KRAS G12D mutation. The regimen combines zoldonrasib (RMC-9805), an oral, mutant-selective, covalent tri-complex RAS(ON) G12D inhibitor developed by Revolution Medicines, with standard-of-care chemotherapy consisting of gemcitabine (a nucleoside metabolic inhibitor) and nab-paclitaxel (an albumin-bound formulation of paclitaxel). Zoldonrasib acts as a molecular glue that recruits cyclophilin A to form a complex that selectively binds and inhibits the active, GTP-bound state of the KRAS G12D mutant protein, thereby blocking downstream oncogenic signaling. In a Phase I/II study (RMC-GI-102), the combination demonstrated an objective response rate of 61% and a disease control rate of 90% in patients with first-line metastatic pancreatic cancer. This combination is being further evaluated in the global, randomized Phase III RASolute 305 trial.

Other names
RMC-9805 + GnPRMC-9805 + gemcitabine + nab-paclitaxelRMC-9805 plus gemcitabine and nab-paclitaxelRMC9805 plus gemcitabine and nab-paclitaxelRMC 9805 plus gemcitabine and nab-paclitaxelzoldonrasib + GnPzoldonrasib + gemcitabine + albumin-bound paclitaxelzoldonrasib + gemcitabine + nanoparticle albumin-bound paclitaxelzoldonrasib plus gemcitabine and nab-paclitaxel
02

Targets

DNAKRAS (Kirsten rat sarcoma viral oncogene homolog)PPIA (Peptidyl-prolyl cis-trans isomerase A)RRM1TUBB (Tubulin (alpha and beta subunits))

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