Nature Medicine Publish Phase III FRUTIGA Results

Hong Kong, Shanghai & Florham Park, NJ - Monday, June 3, 2024: HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM; HKEX: 13) today announces that results from FRUTIGA, HUTCHMED's Phase III trial of fruquintinib in combination with paclitaxel for the treatment of second-line advanced gastric cancer in China, were published in Nature Medicine. Updated efficacy data in key subgroups and data on quality of life (QoL) within this publication were also presented on June 1 at the American Society of Clinical Oncology ("ASCO") 2024 Annual Meeting.

Fruquintinib is a selective oral inhibitor of vascular endothelial growth factor receptors ("VEGFRs") 1, 2 and 3. It works as an anti-cancer therapy by blocking tumor angiogenesis, a proliferation of blood vessels that is critical for cancer growth. The VEGFR pathway plays a key role in the pathogenesis of gastric cancer, which is the fifth most common malignant cancer worldwide, with 1.1 million new cases per year[1]. The FRUTIGA trial results published by Nature Medicine suggest that fruquintinib could be another effective treatment option for gastric cancer patients.

FRUTIGA was a 1:1 randomized, double-blind, Phase III study conducted across 35 sites in China (NCT03223376). It evaluated fruquintinib in combination with paclitaxel chemotherapy, compared with paclitaxel monotherapy, for second-line treatment in 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma. The study was declared positive due to a statistically significant improvement in progression-free survival ("PFS"), one of two dual primary endpoints. Median PFS for patients who received fruquintinib plus paclitaxel was 5.6 months, compared to 2.7 months for those who received paclitaxel monotherapy (stratified hazard ratio ["HR"] = 0.569; p < 0.0001). An improvement was also observed in the dual primary endpoint of median overall survival ("OS"), (9.6 months vs. 8.4 months) but this was not statistically significant. Fruquintinib plus paclitaxel demonstrated statistically significant improvements in multiple other endpoints including objective response rate ("ORR"), disease control rate (DCR) and duration of response (DoR). It was well tolerated, with a safety profile consistent with expectations and previously reported studies.[2]

In further analysis of key subgroups presented at ASCO, PFS and OS results were consistent with the primary analysis compared to the intention-to-treat (ITT) population. There was a clear PFS benefit observed for fruquintinib plus paclitaxel in the majority of subgroups, with particular benefit in both PFS and OS in the intestinal-type and lymph node metastasis subgroups. An exploratory post-hoc analysis for patients with lymph node metastasis revealed superior benefits of fruquintinib versus placebo in PFS, OS, ORR, disease control rate and duration of response. A possible mechanism for this effect is fruquintinib's potent inhibition of VEGFR-‑3, which is closely linked to lymph node metastasis and tumor invasion. Further analysis of patient-reported quality of life ("QoL") revealed no adverse impact on QoL at end of treatment compared to current standard of care. Together, these additional findings, alongside previously reported results, support fruquintinib plus paclitaxel as another treatment option in this indication.

Key results from FRUTIGA were previously disclosed at the American Society of Clinical Oncology (ASCO) Plenary Series Session on February 6, 2024, with the full presentation available here.[3]

Fruquintinib is approved in China and the United States for the treatment of certain patients with metastatic colorectal cancer ("CRC"). A New Drug Application ("NDA") for fruquintinib in combination with paclitaxel for the treatment of second-line advanced gastric or gastroesophageal junction adenocarcinoma in China was accepted for review by the China National Medical Products Administration (NMPA) in April 2023.

About Gastric Cancer

Gastric cancer is a cancer that starts in the stomach. It is the fifth most common cancer worldwide in 2020. It was estimated to have caused approximately 770,000 deaths worldwide.[4] In China, it was estimated that over 478,000 people were diagnosed with gastric cancer, and approximately 374,000 people died from gastric cancer.[5]

About Fruquintinib

Fruquintinib is a selective oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for its potential use as part of combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combinations with other anti-cancer therapies.

Medical Information

[1] World Health Organization. GLOBOCAN 2020. Population fact sheets. China, https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf (2020).

[2] Wang F, et al. Fruquintinib plus paclitaxel versus placebo plus paclitaxel as second-line therapy for advanced gastric or gastro-esophageal junction adenocarcinoma (FRUTIGA): a randomized, multicenter, double-blind, placebo-controlled, phase 3 study [published online ahead of print, 2024 Jun 1]. Nat Med. 2024. DOI: 10.1038/s41591-024-02989-6.

[3] Xu RH, et al., Fruquintinib plus paclitaxel versus paclitaxel as second-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma (FRUTIGA): A randomized, multicenter, double-blind, placebo-controlled, phase 3 study. J Clin Oncol. 2024;42, 438780-438780. DOI: 10.1200/JCO.2024.42.36_suppl.438780.

[4] The Global Cancer Observatory, Stomach Cancer Fact Sheet. Accessed April 6, 2023.

[5] The Global Cancer Observatory, China Fact Sheet. Accessed April 6, 2023.