Revolution rockets on strong pancreatic cancer data

Revolution Medicines thinks it could transform the treatment of pancreatic cancer – one of the hardest forms to treat – based on phase 3 data with its pan-RAS(on) inhibitor daraxonrasib.

The company has just toplined the results of the RASolute 302 trial of daraxonrasib as a second-line treatment for metastatic pancreatic ductal adenocarcinoma (PDAC), showing significant improvements in both progression-free survival (PFS) and overall survival (OS) compared with standard chemotherapy.

All told, median OS in the pan-RAS(on) inhibitor group came in at 13.2 months, compared to 6.7 months with chemo, which was a highly statistically significant 60% improvement with a hazard ratio of 0.4.

That result was for an all-comer population, and the study's primary PFS and OS endpoints in a population with RAS G12-mutant PDAC were also met, although the data has not yet been disclosed. The result was so strong that the trial was ended early, said the company.

Redwood City, California-based Revolution is already planning to file the results with the FDA, and could get a super-speedy review – potentially lasting just one to two months – as daraxonrasib (formerly RMC-6236) was one of the first recipients of a non-transferrable Commissioner's National Priority Voucher (CNPV).

The company is planning to present the full dataset at this year's ASCO cancer congress, which starts at the end of next month, and its upbeat assessment of the results sparked a 41% climb in its shares to give it a market cap of more than $27 billion.

Recall that earlier this year, MSD was rumoured to be interested in a $30 billion takeover bid for the company and – while talks reportedly stalled – there was speculation they could resume if Revolution's clinical trials delivered positive results. Since then, MSD has agreed a $6.7 billion deal to buy Terns Pharma and its promising therapy for chronic myeloid leukaemia (CML).

"The widely anticipated results of this study indicate that daraxonrasib provides a clear and highly meaningful step forward for patients with pancreatic cancer who have experienced progression on prior treatment, typically chemotherapy," said RASolute 302 lead investigator Brian Wolpin, of the Dana-Farber Cancer Institute.

"I believe that this new approach is a very important advance for the field that I expect will be practice-changing," he added.

Along with being very hard to treat, pancreatic cancer is one of the tumour types most driven by RAS mutations, which are seen in around 90% of all cases and fuel aggressive tumour invasiveness and growth.

The pan-RAS category is pretty crowded, with more than a dozen drug candidates in clinical testing, although, Revolution seems to be in the lead, with late-stage trials of daraxonrasib underway in various PDAC settings – including first-line and adjuvant use – and non-small cell lung cancer.

Buoyed by the new data, Revolution promptly launched a stock offering that could be worth upwards of $1 billion.