Hutchmed’s combination of Orpathys (savolitinib) with AstraZeneca’s Tagrisso (osimertinib) cut the risk of disease progression or death by 44 percent against Tagrisso alone in previously untreated patients with EGFR-mutated non-small cell lung cancer and MET overexpression, in the Phase 3 SANOVO trial presented at ESMO on October 26. Median progression free survival was 24.9 months on the combination against 13.8 months on Tagrisso in the intention to treat population, a hazard ratio of 0.56 (95 percent confidence interval 0.43 to 0.74, p below 0.0001). In patients with high MET expression, IHC 3+, the reduction was 55 percent (hazard ratio 0.45), with median progression free survival of 24.8 months against 11.1 months. The company reported an encouraging overall survival trend, with a hazard ratio of 0.48 and median survival of 44.5 months against 34.9 months, on data that are not yet mature.
SANOVO is the companion result to SAFFRON, covered in yesterday’s edition, in which the same combination beat chemotherapy after Tagrisso failure in MET-driven resistance. Together the two trials argue for using the MET inhibitor with Tagrisso at both ends of the treatment course in biomarker selected patients: upfront in SANOVO’s first-line population, and at progression in SAFFRON’s. SANOVO was run in China in patients with MET immunohistochemistry 2+ or 3+ expression, and Hutchmed plans to submit a supplemental new drug application in China for the first-line setting.
The qualification is geography and maturity. SANOVO is a single country trial supporting a China filing, while SAFFRON is the global study carrying applications in the United States, Europe and Japan. The survival figures, striking as a hazard ratio of 0.48 looks, come from an interim look the company itself calls encouraging rather than conclusive.
Hutchmed furnished the results to the SEC on Form 6-K on October 27. For a company whose oncology revenue still depends heavily on partners and on China, two positive Phase 3 readouts for the same combination in one congress weekend is the strongest pipeline statement it has made.