HUTCHMED: TAGRISSO® plus ORPATHYS® shows high response rate in lung cancer with MET overexpression in SAVANNAH trial

HUTCHMED (China) Limited reported promising results from the Phase II SAVANNAH trial, demonstrating that the combination of TAGRISSO® (osimertinib) and ORPATHYS® (savolitinib) yielded high and durable objective response rates (ORR) in patients with EGFR-mutated non-small cell lung cancer (NSCLC) who exhibited MET overexpression and/or amplification. These patients had previously progressed on TAGRISSO® treatment alone. The data, scheduled for presentation at an upcoming medical conference, will also be shared with global regulatory bodies.

TAGRISSO®, a third-generation, irreversible EGFR-TKI, is used extensively in treating NSCLC, while ORPATHYS®, a potent and selective MET tyrosine kinase inhibitor, is being developed and marketed by AstraZeneca and HUTCHMED. ORPATHYS® is also approved in China for treating NSCLC patients with MET exon 14 skipping alterations who have failed prior systemic therapy or are unsuitable for chemotherapy.

Despite the survival benefits of EGFR-targeted therapies for patients with EGFR-mutated NSCLC, resistance often develops, with MET being a prevalent resistance biomarker. In the SAVANNAH trial, approximately 62% of screened patients had tumors with MET overexpression and/or amplification, with about 34% meeting the high MET level criteria upon disease progression.

Dr. Myung-Ju Ahn of Samsung Medical Center, the principal investigator of the SAVANNAH trial, highlighted that while osimertinib significantly improves survival for EGFR-mutated lung cancer patients, resistance due to MET is common. The trial results indicate that adding savolitinib to ongoing osimertinib treatment elicited meaningful responses in patients who had developed resistance, suggesting a viable new treatment option post-osimertinib.

Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, emphasized the importance of a targeted treatment strategy. The SAVANNAH results affirm the benefit of combining ORPATHYS® with TAGRISSO® for patients with MET-driven resistance, underlining the necessity of identifying MET aberrations to continue effective EGFR-mutated lung cancer therapy.

Weiguo Su, CEO and Chief Scientific Officer at HUTCHMED, noted that earlier SAVANNAH trial findings had provided a novel approach to identifying patients likely to benefit from MET-directed therapy. The new positive results further validate this selective, patient-focused approach, potentially offering the first biomarker-driven targeted therapy combination in this context.

Safety and tolerability results from the combination of TAGRISSO® and ORPATHYS® were consistent with the known safety profiles of each drug alone, and no new safety signals were identified.

Further, AstraZeneca's global Phase III SAFFRON trial will evaluate the combination of TAGRISSO® and ORPATHYS® versus platinum-based doublet chemotherapy in patients with EGFR-mutated, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following TAGRISSO® treatment. Patients in this trial will be selected based on the high MET level criteria identified in the SAVANNAH trial.

Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) being the most prevalent type. Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% in Asia, have EGFR mutations. MET overexpression and/or amplification is a common mechanism of resistance to EGFR TKIs in metastatic EGFR-mutated NSCLC. Post-osimertinib progression, about 15-50% of patients exhibit MET aberrations, with the prevalence varying by sample type, detection method, and assay cut-off.

The SAVANNAH trial is a global, randomized, Phase II study sponsored by AstraZeneca, evaluating the efficacy of adding ORPATHYS® to TAGRISSO® in patients with EGFR-mutated, MET-overexpressed and/or amplified NSCLC who have progressed following TAGRISSO® treatment. The trial involved over 360 patients across more than 80 centers worldwide. Key endpoints include ORR, progression-free survival, and response duration.

TAGRISSO® has shown proven clinical activity against both central nervous system metastases and various stages of NSCLC, making it a standard care treatment. ORPATHYS® is an oral MET TKI that has demonstrated clinical activity in advanced solid tumors and is under development for multiple tumor types, including NSCLC, both as a single treatment and in combination with other drugs.

HUTCHMED is a commercial-stage biopharmaceutical company focused on developing and commercializing targeted therapies and immunotherapies for cancer and immunological diseases, with a significant presence in oncology/immunology.