HUTCHMED (China) Limited has released top-line results from its China-based Phase III SANOVO study evaluating ORPATHYS® (savolitinib) plus TAGRISSO® (osimertinib) in previously untreated patients with epidermal growth factor receptor-mutated (EGFRm), MET-overexpressing, locally advanced or metastatic non-small cell lung cancer (NSCLC).
The combination achieved the primary endpoint, reducing the risk of disease progression or death by 44% in the intention-to-treat (IHC 2+/3+) population versus TAGRISSO® alone (progression-free survival [PFS] hazard ratio [HR] 0.56; 95% CI 0.43–0.74; p<0.0001). Median PFS improved to 24.90 months from 13.80 months with monotherapy.
Efficacy was more pronounced in patients with high MET overexpression (IHC 3+). In this subgroup, the risk of progression or death fell by 55% (PFS HR 0.45; 95% CI 0.31–0.66; p<0.0001), with median PFS extending to 24.80 months versus 11.10 months for TAGRISSO® alone.
Overall survival (OS), a key secondary endpoint, also favored the combination. In the intention-to-treat set, ORPATHYS® + TAGRISSO® reduced the risk of death by 52% (OS HR 0.48; 95% CI 0.33–0.68), lengthening median OS to 44.50 months compared with 34.90 months for the control arm. Three-year survival rates reached 67.4% on the combination versus 47.4% with TAGRISSO®.
Safety findings were consistent with the known profiles of each agent. Treatment discontinuation due to adverse events occurred in 14.8% of patients on the combination. Fatal adverse events (excluding disease progression) were comparable between study arms (4.3% vs 4.8%).
SANOVO enrolled 326 Chinese patients, randomizing them 1:1 to receive TAGRISSO® 80 mg once daily plus either ORPATHYS® 300/200 mg twice daily or placebo. HUTCHMED intends to file a supplemental New Drug Application in China to extend ORPATHYS®’s label into the first-line EGFRm, MET-overexpressing NSCLC setting based on these data.
ORPATHYS®, an oral selective MET tyrosine kinase inhibitor co-developed with AstraZeneca, is already approved in China for MET-driven NSCLC and gastric cancers, and in combination with TAGRISSO® for MET-amplified EGFRm NSCLC post-EGFR-TKI progression. The SANOVO readout complements positive results from the SAFFRON and SACHI studies, reinforcing the therapy’s potential across multiple treatment lines.
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