Phase 3 FRUTIGA Study of Fruquintinib Elicits Positive Results in Gastric/GEJ Cancers

The phase 3 FRUTIGA study (NCT03223376) of fruquintinib (Elunate) in combination with paclitaxel in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma met one of its primary end points of statistically significant improvement of progression-free survival (PFS), according to HUTCHMED Limited.¹

While the trial was positive with mostly clinically meaningful data, the other primary end point of the study, overall survival (OS), was not statistically significant per the pre-specified statistical plan. However, an improvement in median OS was demonstrated.

Further, the agent elicited a statistically significant improvement in the studies secondary end points of objective response rate (ORR), disease control rate (DCR), and improved duration of response (DoR). The safety profile of fruquintinib in FRUTIGA was consistent with previously reported studies.

“The combination of fruquintinib and paclitaxel demonstrated significant clinical benefits for these patients in controlling this disease. Our team will continue to analyze the data and discuss these findings with the [National Medical Products Administration] for possible [new drug application] filing,” said Weiguo Su, MD, chief executive officer and chief scientific officer of HUTCHMED, in the press release.

Fruquintinib is a highly selective, potent, oral VEGFR-1, -2 and -3 inhibitor designed to improve kinase selectivity to decrease off-target toxicities, improve tolerability, and provide more consistent target coverage. Preclinical studies have shown fruquintinib to have good tolerability and a low potential for drug-drug interaction. This suggests that the agent may also be useful in combination with other anti-cancer therapies.

In September 2018, the China National Medical Products Administration approved treatment with fruquintinib for patients with metastatic colorectal cancer (mCRC) who previously received fluoropyrimidine, oxaliplatin, and irinotecan, as well as those who received prior anti-VEGF therapy and/or anti-EGFR therapy based on data from the phase 3 FRESCO trial (NCT02314819). Then in June 2020, the FDA granted a fast track designation to fruquintinib for patients with mCRC.

FRUTIGA is a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial evaluating the efficacy and safety of fruquintinib plus paclitaxel compared with paclitaxel alone in patients with advanced gastric cancer who have progressed after first-line standard chemotherapy.²

A total of 703 Chinese patients with histologically or cytologically confirmed gastric or GEJ adenocarcinoma were enrolled in the trial. Eligibility was open to patients with metastatic disease or locally advanced, unresectable disease, disease progression during or within 4 months after the last dose of the first-line therapy, at least 1 measurable lesion, an ECOG performance status of 0-1, and adequate hepatic, renal, heart, and hematologic function.

After enrollment, patients were randomized 1:1 to receive either fruquintinib once daily in a treatment cycle of 4 weeks treatment (3 weeks on and 1 week off) combined with paclitaxel 80mg/㎡ given on day 1, 8, 15 of the 4-week cycle, or placebo combined with the same dose of paclitaxel. The primary end points of the trial are OS and PFS with secondary end points of ORR, DCR, DOR, quality of life, and safety and tolerance evaluated by incidence, severity, and outcomes of adverse events.

The full results are expected to be presented at an upcoming scientific meeting and will be shared with the China National Medical Products Administration.

“By meeting the primary end point of PFS, fruquintinib demonstrated consistent efficacy and safety in gastric cancer indication in addition to its approved colorectal cancer indication. I am extremely excited that fruquintinib may provide a potential new oral treatment option for second line gastric cancer patients based on the FRUTIGA trial,” concluded Rui-Hua Xu, MD, PhD, president of the Sun Yat-Sen University Cancer Center, lead principal investigator of FRUTIGA and Steering Committee Chairman, in the press release.

REFERENCES:

HUTCHMED announces positive topline result in fruquintinib phase III FRUTIGA study in second-line gastric cancer in china. News release. HUTCHMED Limited. November 14, 2022. Accessed November 16, 2022. https://bit.ly/3UV0rfv

A phase III study of fruquintinib in combination with paclitaxel in second line gastric cancer(FRUTIGA) (FRUTIGA). ClinicalTrials.gov. Updated September 2, 2022. Accessed November 15, 2022. https://clinicaltrials.gov/ct2/show/study/NCT03223376