Savolitinib (Orpathys) Receives Conditional Approval in China for MET Exon 14 Skipping Mutation-Positive NSCLC

SHANGHAI, June 23, 2021 /PRNewswire/ -- WORUISA® (savolitinib), co-developed by AstraZeneca and HUTCHMED, has received conditional approval in China for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping mutations, whose disease has progressed following or who are intolerant to standard platinum-based chemotherapy.

Previously, the New Drug Application for savolitinib was granted Priority Review by the National Medical Products Administration of China ("NMPA"). This approval marks the first global regulatory approval for savolitinib, a potent and highly selective oral MET tyrosine kinase inhibitor (TKI).

The number of lung cancer patients in China accounts for over one-third of the global total, while the frequency of MET exon 14 skipping mutation in non-small cell lung cancer (NSCLC) is approximately 2%–3%. This mutation represents a targetable alteration in the MET gene.^1-3This mutation is relatively common in pulmonary sarcomatoid carcinoma (PSC) (13%–22%), a rare and aggressive subtype of NSCLC that is resistant to conventional chemotherapy.^1,4

The approval of savolitinib by China's National Medical Products Administration (NMPA) is based on positive results from a Phase II single-arm clinical trial conducted in China, which enrolled patients with non-small cell lung cancer (NSCLC) harboring such mutations, including those with pulmonary sarcomatoid carcinoma. Results for the primary endpoints of the clinical trial, objective response rate (ORR) and disease control rate (DCR), as assessed by independent review, demonstrated that savolitinib exhibits favorable and durable anti-tumor activity. Further approval is contingent upon the successful completion of confirmatory studies in this patient population.

Mr. Leo Wang, Executive Vice President of AstraZeneca and President, International Markets and China, stated: “The approval of savolitinib will bring greater treatment accessibility and an improved quality of life to lung cancer patients with MET mutations. In the future, AstraZeneca will continue to partner closely with HUTCHMED to explore the application of savolitinib in other tumor types, continuously expanding our multi-pipeline collaborations with local enterprises across different disease areas. AstraZeneca remains committed to working alongside like-minded partners to make relentless efforts for patient health. As the first-in-class drug and the only one approved in China for this patient population, the approval of savolitinib reflects the continuously advancing R&D capabilities of China's innovative pharmaceutical sector. We believe that Chinese innovative medicines will secure more new drug approvals globally in the future, benefiting patients worldwide.”

HUTCHMED Chief Executive Officer Jay Su(Christian Hogg) Mr. stated: "Today we are delighted to announce the first global approval of savolitinib, marking HUTCHMED's third approved innovative oncology drug. Our collaboration agreement with AstraZeneca, signed in late 2011, has demonstrated that the partnership between a Chinese biopharmaceutical company and a global pharmaceutical firm serves as a key driving force in the development of this innovative targeted cancer therapy. This approval stands as a testament to the unwavering dedication and scientific ingenuity of this long-standing alliance. This is just the beginning, and we hope to bring more breakthroughs to patients with MET-mutated tumors in the future."

Professor Lu Shun, Director of the Shanghai Clinical Medical Center for Lung Tumors at Shanghai Chest Hospital, Shanghai Jiao Tong University, stated: “As the first MET inhibitor independently developed in China, we are delighted to see that savolitinib has demonstrated excellent antitumor activity along with favorable tolerability in the treatment of non-small cell lung cancer with MET exon 14 skipping mutations. We believe that the approval of savolitinib will enable more patients with MET exon 14 skipping mutations to benefit from precision targeted therapy. Marking its first global approval, savolitinib not only successfully fills the domestic gap in MET inhibitors, but is also poised to become the first innovative targeted lung cancer drug from China to enter the global market.”

In the Phase II clinical study, with a median follow-up of 17.6 months, the ORR was 42.9% (95% CI 31.1–55.3) among all subjects treated with savolitinib, and the median progression-free survival (PFS) was 6.8 months (95% CI 4.2–9.6). PFS was clinically meaningful across all subgroups, and the ORR was independent of prior treatment or tumor histology. Histological subtypes included patients with lung sarcomatoid carcinoma (40.0%, 95% CI 21.1–61.3) and patients with other non-small cell lung cancer (NSCLC) subtypes (44.4%, 95% CI 29.6–60.0). The DCR in the overall study population was 82.9% (95% CI 72.0–90.8).

The safety and tolerability profile of savolitinib was consistent with previous studies, with no new safety signals identified. Most adverse reactions were Grade 1–2 and were resolved through dose adjustment or drug discontinuation. The incidence of Grade ≥3 adverse events was 45.7%, and the incidence of treatment-related serious adverse events was 24%. One patient with PSC died due to tumor lysis syndrome.

The results of the Phase II clinical trial were presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting (ASCO20), held online in May 2020, and were published in *The Lancet Respiratory Medicine* in June 2021.

As part of a global co-development program conducted jointly with HUTCHMED, the Phase II ORCHARD and SAVANNAH clinical studies are underway to evaluate the combination of savolitinib with osimertinib and other agents to address tumor resistance mechanisms in non-small cell lung cancer, aiming to provide prolonged clinical benefit through combination therapy. The studies also include the treatment of other MET-driven tumors such as papillary renal cell carcinoma, gastric cancer, and gastroesophageal junction cancer.