Savolitinib in patients in China with locally advanced or metastatic treatment-naive non-small-cell lung cancer harbouring MET exon 14 skipping mutations: results from a single-arm, multicohort, multicentre, open-label, phase 3b confirmatory study,The Lancet Respiratory Medicine

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Savolitinib in patients in China with locally advanced or metastatic treatment-naive non-small-cell lung cancer harbouring MET exon 14 skipping mutations: results from a single-arm, multicohort, multicentre, open-label, phase 3b confirmatory study
The Lancet Respiratory Medicine ( IF 38.7 ) Pub Date : 2024-09-10 , DOI: 10.1016/s2213-2600(24)00211-x
Yongfeng Yu ₁ , Qisen Guo ₂ , Yongchang Zhang ₃ , Jian Fang ₄ , Diansheng Zhong ₅ , Baogang Liu ₆ , Pinhua Pan ₇ , Dongqing Lv ₈ , Lin Wu ₉ , Yanqiu Zhao ₁₀ , Juan Li ₁₁ , Zhihua Liu ₁₂ , Chunling Liu ₁₃ , Haichuan Su ₁₄ , Yun Fan ₁₅ , Tongmei Zhang ₁₆ , Anwen Liu ₁₇ , Bo Jin ₁₈ , Ye Wang ₁₉ , Jianying Zhou ₂₀ , Zhihong Zhang ₂₁ , Fengming Ran ₂₂ , Xia Song ₂₃ , Michael Shi ₂₄ , Weiguo Su ₂₄ , Shun Lu ₁ ,

Affiliation

Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Medical Oncology, Shandong Cancer Hospital, Jinan, China.
Department of Lung & Gastrointestinal Oncology, Hunan Cancer Hospital, Changsha, China.
Department of Medical Oncology, Beijing Cancer Hospital, Beijing, China.
Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin, China.
Department of Respiratory Medicine, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Respiratory and Critical Care Medicine, Xiangya Hospital of Central South University, Changsha, China.
Department of Respiratory Medicine, Taizhou Hospital of Zhejiang Province, Taizhou, China.
Department II of Thoracic Medicine, Hunan Cancer Hospital, Changsha, China.
Department of Medical Oncology, Henan Cancer Hospital, Zhengzhou, China.
Department of Medical Oncology, Sichuan Cancer Hospital, Chengdu, China.
Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, China.
Department of Medical Oncology, Cancer Hospital Affiliated to Xinjiang Medical University, Urumqi, China.
Department of Medical Oncology, The Second Affiliated Hospital of PLA Air Force Medical University, Xi'an, China.
Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing, China.
Department of Medical Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, China.
Department of Respiratory Medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Department of Respiratory Oncology, Anhui Provincial Cancer Hospital, Hefei, China.
Department of Medical Oncology, Hubei Cancer Hospital, Wuhan, China.
Department of Medical Oncology, Shanxi Provincial Cancer Hospital, Taiyuan, China.
HUTCHMED, Shanghai, China.

Background

Savolitinib has been approved in China for advanced or metastatic non-small-cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping alterations in previously treated patients and those unable to receive platinum-based chemotherapy. We report results from a treatment-naive cohort of a phase 3b study that was designed to evaluate the efficacy and safety of savolitinib in locally advanced or metastatic METex14-mutated NSCLC.

Methods

This single-arm, multicohort, multicentre, open-label, phase 3b study was done at 48 hospitals in China in adult (≥18 years) patients with locally advanced or metastatic METex14-mutated NSCLC who had not received previous systemic antitumour therapy. Patients with a bodyweight of 50 kg or more and those with a bodyweight of less than 50 kg received savolitinib once daily at 600 mg or 400 mg, respectively, in 21-day cycles. The primary endpoint was objective response rate assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumours, version 1.1. The full analysis set comprised all patients who received at least one dose of study medication, which was used to assess the efficacy endpoints and baseline and safety data. This study is registered with ClinicalTrials.gov (NCT04923945) and is closed to accrual.

Findings

Between Aug 31, 2021, and Oct 20, 2023, 125 treatment-naive patients were assessed for eligibility, of whom 87 were enrolled and received savolitinib. The median age of patients was 70·0 years (IQR 65·2–75·8) and 51 (59%) of 87 patients were male and 36 (41%) were female. In the full analysis set, the IRC-assessed objective response rate was 62% (95% CI 51–72) and the investigator-assessed objective response rate was 60% (49–70), showing a high concordance rate (84%). Treatment-related adverse events were reported in 85 (98%) of 87 patients, with peripheral oedema (54 [62%]) being the most common. Two of these treatment-related adverse events led to death (cardiac failure n=1, unknown reasons n=1).