Key Clinical Summary:

• Design/Population: An ongoing phase 1/2 study evaluated first-line daraxonrasib plus gemcitabine and nab-paclitaxel in patients with RAS-mutated metastatic pancreatic ductal adenocarcinoma.
• Key Outcomes: The combination demonstrated manageable toxicity consistent with known profiles and encouraging early signs of efficacy. Dose intensity remained high, supporting feasibility of combination therapy.
• Clinical Relevance: Daraxonrasib plus gemcitabine and nab-paclitaxel represents clinical promise in this patient population. These findings support further evaluation in randomized phase 3 trials.

Results from a phase 1/2 study demonstrate that first-line daraxonrasib, a novel, multi-selective RAS(ON) inhibitor, plus gemcitabine and nab-paclitaxel shows encouraging preliminary efficacy and manageable safety among patients with RAS-mutated metastatic pancreatic ductal adenocarcinoma.  

These findings were presented by Brian Wolpin, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, at the 2026 American Association for Cancer Research (AACR) Annual Meeting in San Diego, California.

In this study, 40 previously untreated patients received 200 mg of once daily daraxonrasib plus gemcitabine and nab-paclitaxel (administered on days 1 and 15). The primary end point was safety. Key secondary efficacy end points included objective response rate (ORR), disease control rate, and progression-free survival (PFS), in both the intention-to-treat and efficacy-evaluable (n = 39) populations. ctDNA response was assessed in ctDNA-evaluable patients (n = 28). 

At a median follow-up of 9.7 months, the most common treatment-related adverse events of any grade occurring in ≥30% of patients included rash (90%), diarrhea (75%), fatigue (70%), nausea (68%), vomiting (55%), anemia (50%), stomatitis or mucositis (45%), edema peripheral (43%), decreased neutrophil count (43%), decreased platelet count (38%), peripheral neuropathy (38%), alopecia (33%), and increased AST (30%). The most common grade ≥3 treatment-related adverse events occurring in ≥10% of patients were anemia (33%), decreased neutrophil count (20%), fatigue (18%), rash (15%), diarrhea (15%), and stomatitis or mucositis (10%). No treatment-related deaths reported. The mean dose intensity was 82% with daraxonrasib and 80% with gemcitabine plus nab-paclitaxel. 

At efficacy analysis,ORR was 58% and the disease control rate was 90%, with a 6-month PFS rate of 84% in the intention-to-treat population. In efficacy evaluable patients, ORR was 59% and the disease control rate was 92%. Six-month PFS data were immature at analysis. 

Among ctDNA evaluable patients, 96% achieved more than a 50% reduction in RAS VAF, with complete VAF clearance observed in 61% of patients. 

 “Daraxonrasib [plus gemcitabine and nab-paclitaxel] showed manageable safety and compelling preliminary efficacy,” concluded Dr Wolpin. These results support the “initiation of a global 3-arm phase 3 study (RASolute 303).” 

Source:

Wolpin BM, Musher BL, Manji GA, et al. Daraxonrasib plus chemotherapy (CT) as first-line (1L) treatment for patients (Pts) with metastatic pancreatic adenocarcinoma (mPDAC). Presented at AACR Annual. April 17 - 22, 2026; San Diego, California. LB407.