At ASCO, a survival curve prompted a reaction rarely seen in oncology meetings.
As Brian Wolpin presented the Kaplan-Meier data, the room reportedly fell quiet before applause began to build. It culminated in a standing ovation — a response reserved for only a small number of moments in the history of the meeting.
For Alan Sandler, Chief Development Officer at Revolution Medicines, the reaction reflected more than enthusiasm around one study. It represented the significance of a result in pancreatic cancer, a disease where meaningful advances have remained exceptionally difficult to achieve.
A Result That Changed the Atmosphere in the Room
Pancreatic cancer has long been one of the most challenging settings in cancer drug development. Numerous agents have been investigated over the years, often with limited success, particularly in advanced disease.
That is why the survival outcome presented at ASCO carried particular weight.
In the second-line setting, daraxonrasib was associated with a median overall survival of approximately 13.2 months, compared with around 6.6 months in the control group. The result corresponded to a hazard ratio of 0.40, representing a 60% reduction in the risk of death.
“The magnitude of effect is really quite dramatic,” Sandler said.
The control arm performed in line with expectations for second-line pancreatic cancer, where median survival is often in the range of six to seven months. However, the survival reported with daraxonrasib exceeded outcomes historically seen even in many first-line pancreatic cancer studies.
That contrast made the data particularly striking.
Why the Second-Line Setting Matters
Second-line pancreatic cancer remains an area of major unmet need.
Many patients have already received intensive treatment by the time their disease progresses. Options beyond chemotherapy are limited, and outcomes have historically been poor. In this setting, demonstrating a substantial survival improvement against an expected-performing control arm is especially meaningful.
For Sandler, the results also offer clinical validation for a broader scientific approach: targeting RAS signaling in a cancer largely driven by RAS mutations.
Pancreatic cancer is characterized by a high prevalence of RAS alterations, including mutations involving G12D, G12V, G12C, and G13. These alterations help fuel tumour growth and survival, making RAS a central therapeutic target.
Daraxonrasib was developed as a multiselective RAS inhibitor designed to address several RAS variants rather than a single mutation.
“That certainly validates the concept of blocking RAS with our tricomplex inhibitor platform,” Sandler said.
Moving Into the First-Line Setting
Following the second-line results, the development program is now moving into earlier stages of pancreatic cancer treatment.
An ongoing first-line study includes three treatment groups: daraxonrasib alone, daraxonrasib in combination with gemcitabine and nab-paclitaxel, and gemcitabine plus nab-paclitaxel as a standard treatment comparator.
The study is currently enrolling patients.
The design will help assess whether daraxonrasib can provide benefit as a single agent in previously untreated disease, while also examining whether its activity can be strengthened in combination with chemotherapy.
Gemcitabine and nab-paclitaxel remain one of the established treatment options for patients with metastatic pancreatic cancer. Adding a RAS-directed therapy to this backbone could offer an opportunity to change outcomes earlier in the treatment course.
A Study in Resected Pancreatic Cancer
The daraxonrasib program also includes a study for patients with resected pancreatic cancer.
Only a minority of patients are diagnosed at a stage where surgery is possible. Even after complete resection and perioperative treatment, recurrence remains common and long-term outcomes remain limited.
The ongoing study is enrolling patients whose pancreatic cancer has been completely removed surgically. After receiving perioperative therapy through their local treatment teams, participants enter the trial and are randomized to receive daraxonrasib or no further treatment.
The goal is to determine whether continued treatment with daraxonrasib after surgery can improve outcomes in a population where recurrence prevention remains one of the most urgent clinical challenges.
“This actually has the potential not only [to extend] life, but that may increase the cure rate of patients with resected pancreatic cancer,” Sandler said.
From a Landmark Curve to a Broader Development Program
The ASCO response captured the importance of the second-line survival data, but the broader significance may lie in what follows.
The results have opened a path toward testing daraxonrasib across the pancreatic cancer continuum: after progression on prior therapy, in newly diagnosed metastatic disease, and following complete surgical resection.
For a disease often described as one of oncology’s most resistant treatment settings, the development of RAS-directed therapies may mark an important shift in the field.
Written by Nare Hovhannisyan, MD
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