Oral Pancreatic Cancer Drug Daraxonrasib Approved by FDA, Nearly Doubling Survival

The U.S. Food and Drug Administration (FDA) has approved an oral cancer drug that nearly doubled survival in patients with advanced pancreatic cancer.

According to the FDA on the 26th (local time), daraxonrasib, developed by U.S. pharmaceutical company Revolution Medicines, was approved under the brand name Rasonque. The indication is for adults with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or are not candidates for combination systemic therapy.

With the approval, the drug, which had remained in the clinical trial stage, has become an established treatment option. The approval was based on results from the phase 3 RASolute 302 trial involving 500 patients with metastatic pancreatic ductal adenocarcinoma.

In the trial, the median overall survival was 13.2 months among patients who received daraxonrasib, approximately twice the 6.7 months observed among patients who received standard chemotherapy. The risk of death was 60% lower than with chemotherapy.

Daraxonrasib is an oral drug that inhibits RAS proteins and is classified as a “RAS(ON) multi-selective” inhibitor. It acts on a key molecular pathway involved in tumor cell growth and proliferation.

Specifically, it acts on KRAS, a variant of the RAS protein. KRAS functions as an accelerator for tumor growth, while RAS genes continuously signal cancer cells to grow and divide, driving cancer growth and metastasis. More than 90% of patients with the most common form of pancreatic cancer have KRAS gene mutations.

Daraxonrasib works by switching off the KRAS protein, regardless of whether a specific genetic mutation is present, thereby stopping cancer growth. Brazilian oncologist Mauro Donadio said, “KRAS was previously considered essentially an impossible target to attack,” adding, “With an oral drug that blocks this signaling pathway producing results on this scale, the treatment landscape for these patients has been completely transformed.”

The detailed clinical results were also encouraging. Approximately one-third of patients who received daraxonrasib experienced tumor stabilization or regression, substantially exceeding the 10% rate in the chemotherapy group. The objective response rate, meaning the proportion of patients whose tumors shrank or disappeared, was 33.2% in the daraxonrasib group and 11.8% in the chemotherapy group.

Donadio explained, “Patients whose disease progressed after first-line palliative treatment were randomly assigned to receive either 300 mg of daraxonrasib daily or standard chemotherapy,” adding, “Among patients who received the oral drug, progression-free survival doubled from 3.5 months to 7 months, overall survival doubled from 6 months to 13 months, the risk of death or progression fell by approximately 60%, and the response rate tripled from 11% to 33%.”

There was also a difference in quality of life. The time to deterioration, measured based on pain and patient-reported quality of life, was significantly longer in the daraxonrasib group than in the chemotherapy group.

The safety profile was also favorable. The most common adverse event was skin rash, which occurred in 86.3% of patients who received daraxonrasib after starting treatment. However, according to the researchers, most cases were manageable with antibiotics and topical steroids.

Only 1.2% of patients in the daraxonrasib group discontinued treatment because of treatment-related adverse events, substantially lower than the 11.2% in the chemotherapy group. Donadio said, “This is a particularly important tolerability measure for patients already weakened by severe disease,” adding, “A discontinuation rate of 1.2% is meaningful in itself.”

Pancreatic cancer is considered one of the deadliest cancers in oncology. The 5-year survival rate for patients with metastatic disease is only 3%, and approximately 80% of patients are diagnosed when the disease is already advanced or metastatic. More than half are diagnosed only after the cancer has already spread.

Brian Wolpin, MD, the study’s lead investigator at Dana-Farber Cancer Institute, acknowledged that standard chemotherapy in the second-line setting is not as effective as hoped. Against this backdrop, the approval is considered significant.

Revolution Medicines is already testing daraxonrasib at earlier stages of disease and in combination with other treatments. In May, the FDA authorized the company to launch an expanded access program before full approval.

Donadio said, “The next step is to monitor regulatory proceedings in other countries, including Brazil,” adding, “If it is approved, we must closely follow the regulatory process to ensure that the drug also reaches Brazil’s health care system.”