HUTCHMED's Breakthrough: ORPATHYS® and TAGRISSO® Combination for Lung Cancer

HUTCHMED (China) Limited has recently announced a significant milestone in the fight against lung cancer. The company has received Breakthrough Therapy Designation (BTD) from China's National Medical Products Administration (NMPA) for the combination of ORPATHYS® (savolitinib) and TAGRISSO® (osimertinib) in treating certain lung cancer patients who have progressed on EGFR inhibitor therapy. This article explores the implications of this development and its potential impact on lung cancer treatment.

The combination of ORPATHYS® and TAGRISSO® targets acquired resistance to EGFR inhibitors in lung cancer patients with MET amplification. ORPATHYS® is a potent and highly selective MET tyrosine kinase inhibitor, while TAGRISSO® is a third-generation, irreversible EGFR TKI. MET amplification is a major mechanism of resistance to both first/second-generation EGFR TKIs and third-generation EGFR TKIs like osimertinib, occurring in approximately 15-50% of patients who experience disease progression post-osimertinib treatment. By targeting both MET and EGFR pathways, this combination therapy aims to overcome resistance and improve patient outcomes.

The ongoing SACHI trial in China is investigating the efficacy and safety of this combination compared to standard chemotherapy in patients with locally advanced or metastatic EGFR mutation-positive NSCLC with MET amplification after failure of EGFR inhibitor therapy. The primary endpoint of the study is progression-free survival (PFS) as assessed by investigators, with other endpoints including PFS assessed by an independent review committee, overall survival (OS), objective response rate (ORR), duration of response (DoR), disease control rate (DCR), time to response (TTR), and safety. The NMPA's Breakthrough Therapy Designation indicates that the development and review of this therapy may be expedited, addressing patients' unmet needs more quickly.

The ORPATHYS® and TAGRISSO® combination has shown promising results in clinical trials, with expected improvements in progression-free survival (PFS) and overall survival (OS) for lung cancer patients. The TATTON (NCT02143466) and SAVANNAH (NCT03778229) studies demonstrated encouraging results, leading to the initiation of three Phase III trials: SACHI (NCT05015608), SANOVO (NCT05009836), and SAFFRON (NCT05261399). These trials aim to further validate the efficacy and safety of this combination therapy in various lung cancer patient populations.

In conclusion, HUTCHMED's Breakthrough Therapy Designation for the ORPATHYS® and TAGRISSO® combination represents a significant advancement in the treatment of lung cancer. This combination therapy targets a common mechanism of resistance to EGFR inhibitors, offering hope for improved outcomes in patients with locally advanced or metastatic EGFR mutation-positive NSCLC with MET amplification. As the SACHI trial and other ongoing studies continue to evaluate the efficacy and safety of this combination, investors should monitor the progress of this promising treatment option.