China’s NMPA Grants Breakthrough Therapy Designation to Savolitinib Plus Osimertinib in EGFR+ NSCLC

China’s National Medical Products Administration’s Center for Drug Evaluation has granted breakthrough therapy designation to the combination of savolitinib (Orpathys) and osimertinib (Tagrisso) for the treatment of patients with locally advanced or metastatic EGFR-mutant non–small cell lung cancer (NSCLC) with MET amplification after disease progression on EGFR inhibitor therapy.1

The combination is under evaluation in China in the ongoing multicenter, open-label, randomized, controlled, phase 3 SACHI trial (NCT05015608). The study is evaluating the efficacy and safety of the combination of savolitinib and osimertinib vs platinum-doublet chemotherapy with pemetrexed plus cisplatin or carboplatin in patients with EGFR-mutant, locally advanced or metastatic MET-amplified NSCLC after progression on EGFR inhibitor therapy.

To be eligible for enrollment patients must be between the ages of 18 and 75 years old and have histologically or cytologically confirmed unresectable and not suitable for radical concurrent chemoradiotherapy, locally advanced, or metastatic stage IIIB, IIIC, or IV disease in accordance with the Eighth TNM staging edition for lung cancers.2 Additionally, patients must have EGFR sensitizing mutations prior to first-line EGFR TKI therapy, radiologically documented disease progression after frontline therapy with presence of MET amplification, measurable lesions, an ECOG performance status of 0 or 1, adequate bone marrow reserve or organ function, and expected survival greater than 12 weeks.

In the trial patients in the experimental arm will receive oral savolitinib once daily in combination with oral osimertinib once daily in 21-day cycles until disease progression, death, adverse effect leading to discontinuation, or consent withdrawal.In the control arm patients will receive pemetrexed plus platinum on day 1 of every 21-day cycle.

The primary end point of the study is investigator-assessed progression-free survival (PFS). Secondary end points include PFS according to independent review committee assessment, overall survival, objective response rate, duration of response, disease control rate, time to response, and safety.1,2 In November 2021, Hutchmed had announced that the first patient had been dosed in the trial.3

In 2023, the FDA granted fast track designation to the combination of savolitinib and osimertinib in this population.1 Earlier in October, Hutchmed announced that the combination produced durable responses in patients with EGFR-mutant, MET-overexpressed and/or -amplified NSCLC with disease progression on osimertinib.4

The combination will be subject to further study in the global phase 3 SAFFRON trial (NCT05261399) wherein patients with EGFR-mutant, MET-overexpressed and/or -amplified locally advanced or metastatic NSCLC whose disease progressed on osimertinib will be randomly assigned to treatment with savolitinib plus osimertinib or platinum-doublet chemotherapy.1

The combination is also under evaluation vs osimertinib alone as frontline therapy in patients with EGFR-mutant and MET-overexpressed NSCLC in the ongoing phase 3 SANOVO trial (NCT05009836) in China.

Independent of osimertinib, savolitinib is also being developed for the treatment of patients with non–clear cell renal cell carcinoma (RCC), following activity as a single agent and in combination with durvalumab (Imfinzi) in patients with MET-driven papillary RCC.

References

1. Hutchmed announces breakthrough therapy designation in China for Orpathys and TAGRISSO combination in certain lung cancer patients after disease progression on EGFR inhibitor therapy. News release. Hutchmed. December 12, 2024. Accessed December 12, 2024. https://www.hutch-med.com/orpathys-tagrisso-china-breakthrough/
2. Study on savolitinib combined with osimertinib in treatment of advanced NSCLC with MET amplification (SACHI). ClinicalTrials.gov. March 30, 2023. Accessed December 12, 2024. https://clinicaltrials.gov/study/NCT05015608
3. 3.Hutchmed and AstraZeneca initiate SACHI phase III trial of Orpathys and Tagrisso combination in certain lung cancer patients in China after progression on EGFR inhibitor therapy. News release. Hutchmed. November 24, 2021. Accessed December 12, 2024. https://www.hutch-med.com/sachi-phase-iii-trial-initiated/
4. Hutchmed announces that Tagrisso plus Orpathys demonstrated high, clinically meaningful response rate in lung cancer patients with high levels of MET overexpression and/or amplification in SAVANNAH phase II trial. News release. Hutchmed. October 16, 2024. Accessed December 12, 2024. https://www.hutch-med.com/tagrisso-orpathys-savannah-phase-ii-trial/