Revolution Medicines is progressing its rat sarcoma (RAS) inhibitor, daraxonrasib, to Phase III trials in pancreatic ductal adenocarcinoma (PDAC).
This follows the positive outcome of the Phase I/Ib trial (NCT05379985), which explored the safety and efficacy of the multi-selective inhibitor in a range of advanced solid tumours, including PDAC, non-small cell lung cancer (NSCLC) and colorectal cancer.
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After a long-term follow-up of daraxonrasib’s activity as a monotherapy in second-line metastatic PDAC, daraxonrasib exhibited an objective response rate (ORR) of 35% in patients with a RAS G12X mutation, or 29% in patients with any RAS mutation.
Disease control rates (DCR) for these patient populations were 92% and 95%, respectively, while median progression-free survival (PFS) stood at 8.5 and 8.1 months.
Meanwhile, overall survival (OS) was 13.1 and 15.6 months in these patient populations – a marked improvement from the 7.4-month OS rate seen in patients treated with standard of care (SoC) nab‐paclitaxel/gemcitabine (GnP) in a retrospective analysis.
Daraxonrasib also exhibited a favourable safety profile, with no more than 10% of patients experiencing severe treatment-related adverse events (TRAEs) marked Grade 3. There were no new safety signals observed.
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By GlobalDataTo further explore the efficacy and safety of daraxonrasib in this setting, Revolution is currently recruiting for the Phase III RASolute 302 trial, which is on track to complete global recruitment by the end of this year. The biotech expects a data readout from this trial in 2026.
Daraxonrasib shines in the first line
The Phase I/Ib trial also evaluated daraxonrasib’s potential in the first-line setting, both as a monotherapy and a combination with the chemotherapy regimen GnP. In the monotherapy arm, patient ORR was 47%, while DCR was 89% after a median follow-up of 9.3 months – though the biotech will need to collect follow-up data to ascertain the durability of the drug’s benefit in the first-line.
At a median follow-up of 6.9 months, daraxonrasib also showed promise when combined with chemotherapy, with patient ORR and DCR reaching 55% and 90%, respectively. The safety profile of the drug was consistent with prior findings in both treatment arms.
Revolution will now conduct the Phase III RASolute 303 trial – looking into the drug’s potential as a monotherapy and combination agent alongside SoC GnP chemotherapy in front-line PDAC. The biotech plans to initiate the study in Q4 2025.
Expanding the PDAC treatment landscape
Currently, the prognosis for patients with pancreatic cancer is the worst of all the solid tumours, with the five-year survival of patients diagnosed with the condition sitting at less than 7%.
The treatment landscape has also remained stagnant, relying on chemotherapy regimens such as GnP, which often show limited efficacy.
However, pharma and biotech are now looking to broaden the treatment horizon for PDAC, with seven drugs now in global Phase III trials in the indication, according to GlobalData’s Intelligence Center.
GlobalData is the parent company of Clinical Trials Arena.
This includes a Phase III study (NCT06953999) run by Chinese biopharma Akeso, which is exploring the potential of its programmed cell death protein 1/vascular endothelial growth factor (PD-1/VEGF) bispecific, ivonescimab, in the indication.
In a previous interview, Dr Balasz Halmos, thoracic oncologist at the Albert Einstein College of Medicine and Montefiore Medical Centre, told Clinical Trials Arena that PD-1/VEGF bispecifics are stirring up “a lot of excitement” in the oncology field, as he believes they could “turn the market upside down”.
GlobalData analysts appear to be echoing this sentiment, as they forecast that ivonescimab will generate $8.9bn for Akeso in 2031 if approved.
However, analysts also have high hopes for Revolution’s daraxonrasib, which analysts predict will reach blockbuster status by 2029, earning $2.1bn for the biotech by 2031.
