Zoldonrasib

The RAS revolution is officially here, thanks to the FDA's approval of Rasonque (daraxonrasib) for adults with metastatic pancreatic ductal adenocarcinoma (PDAC) on Wednesday. Revolution Medicines' RAS inhibitor was greenlit less than five months after it first revealed "practice-changing" data suggesting the candidate could help patients live twice as long as standard chemotherapy (see – Spotlight On: Daraxonrasib set to revolutionise pancreatic cancer treatment landscape). "This drug showed unprecedented results in an area of high unmet need," said Angelo de Claro, director of the FDA's Oncology Center of Excellence, in an agency announcement. The stellar data backing Rasonque also helped it bag a Commissioner’s National Priority Voucher for a speedy review — with its approval coming just a month after the FDA accepted the drug application, and 6.5 months before its official PDUFA date. Wednesday's clearance covers the RAS inhibitor's use in patients with PDAC who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy. The backbone of Rasonque's supporting data is the Phase III RASolute 302 trial, which randomised 500 patients with previously treated disease to receive the once-daily oral tablet or physician's choice of chemotherapy. In April, Revolution reported that its candidate led to median overall survival (OS) of 13.2 months versus 6.7 months for standard chemotherapy. An expert who spoke with FirstWord after the readout called the results "very gratifying" because it was "the first time ever that we have been able to show that something beyond chemotherapy improves survival" in PDAC (see – KOL Views Q&A: Revolution's breakthrough with daraxonrasib will reverberate throughout pancreatic cancer landscape). Revolution shared further details from RASolute 302 at the American Society of Clinical Oncology (ASCO) meeting, showing that Rasonque's OS benefit was seen not only in patients carrying a RAS G12 variant — which drives more than 90% of metastatic PDAC cases — but in all-comers as well. The updated data also demonstrated a median progression-free survival (PFS) for the drug of 7.3 months in RAS G12-mutant patients and 7.2 months in the overall patient population, roughly double the rates seen in patients receiving chemotherapy Now with an FDA approval in-hand, physicians will likely be eager to start their patients on Rasonque, judging by the results of a recent FirstWord survey. Not only did the vast majority of physicians — 94% — view the RASolute 302 data as practice-changing for second-line PDAC, respondents also signalled a broad willingness to prescribe the drug off-label in the first-line setting (see – Physician Views Results: Oncologists overwhelmingly positive on second- and first-line potential of Revolution Medicines' daraxonrasib in pancreatic cancer). Revolution is already working to duplicate Rasonque's practice-changing PDAC results in other cancer settings. In addition to a pair of PDAC studies in frontline and resectable disease, the company is running the Phase III RASolve 301 study in patients with previously-treated non–small-cell lung cancer, and the Phase I/II open-label platform study in patients with colorectal cancer. Speaking with FirstWord during ASCO, Chief Development Officer Alan Sandler said the drugmaker is also pursuing potential combinations of Rasonque with Summit Therapeutics' PD-1/VEGF bispecific ivonescimab, and with two PRMT5 inhibitors from Tango Therapeutics and Bristol Myers Squibb (see – ASCO ViewPoints: How Revolution plans to maintain its pan-RAS lead). The company is also exploring a Rasonque combination with zoldonrasib, its oral selective covalent inhibitor of RAS G12D. In a Phase I study, the duo achieved a 50% overall response rate and a 97% disease control rate in 30 previously treated patients with KRAS G12D-mutant solid tumours. Median PFS reached 9.6 months, with 71% of patients still progression-free at the six-month mark. "From a scientific perspective, we're not stopping with what we have now. We're also interested in looking at other modalities," Sandler told FirstWord during ASCO. The content above comes from the network. if any infringement, please contact us to modify.