The US Food and Drug Administration (FDA) has approved Revolution Medicines’ RASONQUE™ (daraxonrasib) tablets for adults with metastatic pancreatic adenocarcinoma (PDAC) who have received at least one previous systemic treatment or are not candidates for multi-agent systemic therapy.

RASONQUE is the first approved medicine from a new class of RAS(ON) multi-selective and mutant-selective inhibitors. It is an oral, once-daily treatment and can be used in patients with metastatic PDAC regardless of whether a RAS tumour mutation has been identified. The approved use does not require a companion diagnostic test.

Pancreatic cancer is often diagnosed at an advanced stage and is driven largely by abnormal RAS signalling. The approval provides a targeted treatment option for patients with metastatic disease who have limited treatment choices.

Phase 3 trial supports approval

The FDA approval is based on results from the global, randomised Phase 3 RASolute 302 trial, which compared RASONQUE with investigator-selected cytotoxic chemotherapy in patients with previously treated metastatic PDAC.

The trial met its primary and key secondary endpoints in both the RAS G12 mutant group and the overall population, which included patients with and without an identified RAS tumour mutation.

Among the overall study population, RASONQUE reduced the risk of death by 60% compared with chemotherapy. Median overall survival was 13.2 months with RASONQUE, compared with 6.7 months with chemotherapy.

RASONQUE also reduced the risk of disease progression or death by 51%. Median progression-free survival was 7.2 months with RASONQUE versus 3.6 months with chemotherapy. The results were generally consistent in patients with RAS G12 mutations.

Quality-of-life results

The study also assessed patient-reported outcomes because metastatic pancreatic cancer can cause a high level of symptoms and affect daily life.

RASONQUE delayed deterioration in overall health status and pain compared with chemotherapy. The median time to deterioration in global health status was 5.7 months with RASONQUE, compared with 2.6 months with chemotherapy.

The treatment also delayed clinically relevant worsening of pain, with a median time to deterioration of 9.2 months compared with 3.8 months for chemotherapy.

RASONQUE showed a manageable safety and tolerability profile. The most common adverse reactions, occurring in at least 20% of patients, included rash, diarrhoea, stomatitis, nausea, vomiting, abdominal pain, oedema, reduced appetite and haemorrhage.

The approval marks the introduction of a targeted RAS-directed treatment option for adults with metastatic pancreatic cancer following previous systemic therapy or for those who cannot receive multi-agent systemic treatment.

 

Source: revmed.com

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