FDA Gives Priority Review to Fruquintinib in Metastatic Colorectal Cancer

The FDA has accepted and granted priority review to a new drug application (NDA) for fruquintinib (Elunate) in the treatment of patients with previously treated metastatic colorectal cancer (CRC), according to a press release from Takeda and HUTCHMED Limited.¹

Manufacturers hypothesize that the investigational, highly selective VEGFR inhibitor fruquintinib may improve kinase selectivity by minimizing off-target toxicities, thereby improving tolerability and target coverage in blocking tumor angiogenesis.

If approved, fruquintinib would be the first and only VEGFR-1, -2, and -3 inhibitor to be available in the United States for the treatment of patients with previously treated metastatic CRC.

Supporting data for the NDA in this indication come from the phase 3 FRESCO-2 trial (NCT04322539) as well as the Chinese phase 3 FRESCO trial (NCT02314819). In the FRESCO-2 trial, investigators highlighted a median overall survival (OS) of 7.4 months with fruquintinib plus best supportive care vs 4.8 months with placebo and best supportive care (Hazard ratio [HR], 0.66; 95% CI, 0.55-0.80; P <.001).²

Data from the FRESCO-2 trial also indicated a median progression-free survival of 3.7 months in the fruquintinib arm vs 1.8 months in the placebo arm (HR, 0.32; 95% CI, 0.27-0.39; P <.001). Additionally, the disease control rate was 55.5% vs 16.1%, and the overall response rate was 1.5% vs 0.0% in each respective arm.

“There are significant needs for patients with [previously treated metastatic CRC] in the U.S., and we believe fruquintinib has the potential to address these needs regardless of patients’ biomarker status,” Awny Farajallah, MD, head of Global Medical Affairs Oncology at Takeda, said in the press release.

Manufacturers hypothesize that the investigational, highly selective VEGFR inhibitor fruquintinib may improve kinase selectivity by minimizing off-target toxicities, thereby improving tolerability and target coverage in blocking tumor angiogenesis.

Investigators of the multi-regional, phase 3 FRESCO-2 trial administered treatment to a total of 691 patients with previously treated metastatic CRC. Patients were randomly assigned to receive fruquintinib or matched placebo plus best supportive care.

The primary end point of the FRESCO-2 trial was OS.

Patients 18 years and older with histologically or cytologically documented metastatic CRC and disease progression on treatment with trifluridine/tipiracil (Lonsurf) or regorafenib (Stivarga) were eligible for enrollment on the trial. Additional inclusion criteria included having an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1 criteria, a life expectancy of more than 12 weeks, and treatment with a BRAF inhibitor for those with BRAF-mutated tumors.

Those with uncontrolled hypertension or a history of or active gastric ulcer or active hemorrhage of an unresected gastrointestinal tumor were unable to enroll on the study. Patients were also unsuitable for enrollment if they had clinically significant cardiovascular disease, palliative radiotherapy for bone metastases or lesions within 2 weeks of beginning study treatment, brachytherapy within 60 days of beginning study treatment, or known human immunodeficiency virus infection.

Investigators originally submitted the NDA for fruquintinib in the treatment of metastatic CRC to the FDA in March 2023.³ The application submission was supported by the phase 3 FRESCO-2 trial.

“This FDA submission is a significant milestone for patients in the U.S. with metastatic CRC, one of the most common and deadly cancers in the US and worldwide,” Michael Shi, MD, head of Research and Development and chief medical officer at HUTCHMED, said at the time of the NDA submission.

References

1. Takeda and HUTCHMED announce new drug application (NDA) for fruquintinib for treatment of previously treated metastatic colorectal cancer granted priority review. News release. Takeda and HUTCHMED. May 25, 2023. Accessed May 26, 2023. bit.ly/43u0FOw
2. Dasari NA, Lonardi S, Garcia-Carbonero R, et al. FRESCO-2: a global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Ann Oncol. 2022;33(suppl 7):S808-S869. doi:10.1016/annonc/annonc1089
3. HUTCHMED completes rolling submission of NDA to U.S. FDA for fruquintinib for the treatment of refractory metastatic colorectal cancer. News release. HUTCHMED. March 30, 2023. Accessed May 26, 2023. http://bit.ly/3Gcody3