NEW YORK – Hutchmed on Monday said it has received a $15 million milestone payment from AstraZeneca because it is gearing up to start a global Phase III trial of its MET inhibitor Orpathys (savolitinib) in non-small cell lung cancer patients with EGFR-mutated and MET-driven tumors.
Hong Kong and Shanghai-based Hutchmed said that in mid-2022 it will begin enrolling NSCLC patients into the SAFFRON study, which will explore the activity of Orpathys in combination with AstraZeneca's EGFR inhibitor Tagrisso (osimertinib). Patients must have progressed on prior Tagrisso treatment and have EGFR mutations and MET aberrations characterizing their tumors.
Hutchmed and AstraZeneca inked a global licensing, codevelopment, and commercialization agreement for Orpathys in 2011. Under that deal, AstraZeneca made an initial payment of $20 million with Hutchmed eligible for additional milestone payments. According to Hutchmed, through the course of their collaboration, AstraZeneca has paid it $85 million out of a total $140 million in upfront, development, and first-sale milestone payments.
Orpathys is already marketed in China for NSCLC patients with MET exon 14 skipping tumor alterations who have progressed on systemic therapy or cannot receive chemotherapy. AstraZeneca's Tagrisso is a third-generation EGFR inhibitor that is globally available for several EGFR-mutated NSCLC indications.
The companies decided to study the combination of these drugs in NSCLC patients with MET aberrations and EGFR mutations in the SAFFRON trial based on the signals seen in another study, called SAVANNAH. In that trial, AstraZeneca is exploring the activity of the Tagrisso-Orpathys combo in advanced, EGFR-mutated NSCLC patients who have become resistant to Tagrisso due to MET amplification or overexpression.
Based on results from SAVANNAH, Hutchmed and AstraZeneca last year said they would launch a Phase III trial, called SANOVO, in China, in which advanced NSCLC patients with MET-overexpressing and EGFR-mutated tumors would receive the Tagrisso-Orpathys combo as a first-line treatment.
Up to 25 percent of NSCLC patients in the US and Europe, and up to 40 percent of patients in Asia have EGFR-mutated tumors. This subset of patients responds particularly well to EGFR inhibitors, but over time, most become resistant to therapy, often through acquired aberrations in MET.
Up to 4 percent of NSCLC patients have tumors driven by MET exon 14 skipping mutations. Orpathys targets lung tumors with these and other MET mutations or amplifications.