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

— New data demonstrate efficacy for the oral treatment combination to address MET-driven resistance in EGFR-mutated lung cancer —

— MET is a common biomarker in this setting for patients who develop resistance to EGFR targeted therapies —

Hong Kong, Shanghai & Florham Park, NJ — Wednesday, October 16, 2024: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:​HCM; HKEX:​13) today announces positive high-level results from the SAVANNAH Phase II trial that showed TAGRISSO^® (osimertinib) plus ORPATHYS^® (savolitinib) demonstrated a high, clinically meaningful and durable objective response rate (“ORR”) for patients with epidermal growth factor receptor-mutated (“EGFRm”) non-small cell lung cancer (“NSCLC”) with high levels of MET overexpression and/or amplification, defined as IHC90+ and/or FISH10+, whose disease progressed on treatment with TAGRISSO^®. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. In 2023, TAGRISSO^® plus ORPATHYS^® received Fast Track designation from the US Food and Drug Administration (FDA) in this setting.

ORPATHYS^® is an oral, potent, and highly selective MET tyrosine kinase inhibitor (“TKI”) being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca. It is approved in China for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy.

While EGFR-targeted therapy can provide a substantial survival benefit to patients with EGFRm NSCLC, most will eventually develop resistance to their treatment, with MET being a common resistance biomarker.[i] Among patients screened for enrollment in SAVANNAH, an estimated 62% had tumors with MET overexpression and/or amplification, and approximately 34% met the defined high MET level cut-off upon clinical progression.

Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and principal investigator in the SAVANNAH Phase II trial, said: “Osimertinib can provide patients with EGFR-mutated lung cancer unprecedented survival and has transformed the treatment landscape, but patients can develop resistance due to genes like MET – a common resistance biomarker. These results show that adding savolitinib, a selective MET-inhibitor, while continuing osimertinib treatment helped to deliver a meaningful response among patients whose disease progressed, providing a potential new treatment option following standard-of-care osimertinib.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “These positive SAVANNAH results show the benefit of a targeted treatment approach in EGFR-mutated lung cancer patients who experience MET-driven resistance. The improved response rates from ORPATHYS^® added to TAGRISSO^®, which is the backbone EGFR-mutated lung cancer therapy, reinforce the importance of identifying MET aberration and validate our combination strategy to address resistance while allowing continued TAGRISSO^® treatment.”

Weiguo Su, Chief Executive Officer and Chief Scientific Officer, HUTCHMED, said: “Previous results from the SAVANNAH Phase II trial provided a novel biomarker approach for identifying patients with MET overexpression and/or amplification who are most likely to benefit from a MET-directed therapy, an existing unmet need. These new, positive results affirm our selective, patient-centric approach, which could allow us to deliver the first biomarker-driven targeted therapy combination option in this setting.”

The safety and tolerability of TAGRISSO^® plus ORPATHYS^® was consistent with the known safety profiles of the combination and each treatment alone. No new safety signals were identified.

In August 2022, initial positive ORR results from the SAVANNAH trial were presented at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (WCLC).

The global SAFFRON Phase III trial sponsored by AstraZeneca will further assess the TAGRISSO^® plus ORPATHYS^® combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following TAGRISSO^®. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH.

[i]    Del Re M, et al. Understanding the Mechanisms of Resistance in EGFR-Positive NSCLC: From Tissue to Liquid Biopsy to Guide Treatment Strategy. Int J Mol Sci. 2019;20(16): 3951.