Fruquintinib Enters Phase 3 Trial for Metastatic Colorectal Cancer

December 7, 2020 - The survival benefit of the novel agent fruquintinib will be tested during the phase 3 FRESCO-2 trial in patients with metastatic colorectal cancer who are either intolerant to or have received 3 prior lines of chemotherapy.

The survival benefit of the novel agent fruquintinib (HMPL-013) will be tested during the phase 3 FRESCO-2 trial (NCT04322539) in patients with metastatic colorectal cancer (mCRC) who are either intolerant to or have received 3 prior lines of chemotherapy.1

Most recently, the highly selective and potent VEGF inhibitor was granted a fast track designation by the FDA in June 2020 in patients with mCRC who had previously been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, VEGF-directed therapy, and—if the patient is RAS wild-type—EGFR-directed therapy.2

The agent was most recently examined in the phase 3 FRESCO study, wherein 97.1% of patients (n = 404; fruquintinib, 5 mg, n = 278; placebo, n = 138) completed the trial.3 Here, fruquintinib was found to significantly prolong median overall survival vs placebo at 9.3 months and 6.6 months, respectively (HR, 0.65; 95% CI, 0.51-0.83; P < .001). The median progression-free survival was 3.7 months vs 1.8 months, respectively (HR, 0.26; 95% CI, 0.21-0.34; P < .001).

Fruquintinib, given orally, is designed to prevent new blood vessels from growing from existing vessels that work to supply blood flow to tumors.

The phase 3 FRESCO-2 trial is a global, randomized, double-blind, placebo-controlled, multicenter phase 3 study that will compare the efficacy and safety of fruquintinib plus best supportive care vs placebo plus best supportive care.4 The trial plans to enroll 520 patients who will be randomized 2:1 to fruquintinib or placebo.

“This is the only phase 3 trial that I am aware of for metastatic colorectal cancer in the United States at this time,” said senior national principal investigator Cathy Eng, MD, FACP, FASCO, David H. Johnson Chair in Surgical and Medical Oncology; co-leader, Gastrointestinal Cancer Research Program; professor of medicine; co-director of gastrointestinal oncology; vice-chair of the SWOG Gastrointestinal Committee; and director of VICC Young Adults Cancers Initiative at Vanderbilt-Ingram Cancer Center.

To be eligible for enrollment, patients need to have progressed on or had resistance to chemotherapy, biologics, and trifluridine/tipiracil (TAS-102; Lonsurf) or regorafenib (Stivarga). For patients whose tumors are microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR), progression on an immune checkpoint inhibitor is also required, should it be an available and appropriate treatment.

Patients must be at least 18 years old with histologically and/or cytologically documented mCRC with documented RAS, BRAF, MSI, or MMR status. Patients who received adjuvant oxaliplatin must have progressed within 6 months of completing the therapy. Additionally, an ECOG performance status of 0 or 1 is required, along with an expected survival longer than 12 weeks.

Exclusion criteria include patients with a neutrophil count of less than 1.5×109/L, a platelet count of less than 100×109/L, and hemoglobin of less than <9.0 g/dL. Patients cannot receive a blood transfusion within 1 week of enrollment, in order to increase eligibility likelihood. Those with uncontrolled hypertension, a history of or active gastric/duodenal ulcer or ulcerative colitis, active hemorrhaging of an unresected gastrointestinal tumor, history of perforation or fistulas, or a history or presence of hemorrhaging from any other site 2 months prior to screening are not permitted to enroll on the trial.

The primary outcome of the study is OS.

Previously, fruquintinib was approved in June 2018 by the National Medical Products Administration in China for patients with mCRC who have received at least 2 prior standard of care treatments based on the results of the FRESCO study.


  1. New drug for metastatic colorectal cancer enters phase 3 trial. News release. VUMC Reporter. November 18, 2020. Accessed November 24, 2020.
  2. Chi-Med announces fruquintinib granted US FDA fast track designation for metastatic colorectal cancer. News release. Chi-Med. June 18, 2020. Accessed November 24, 2020.
  3. Li J, Qin S, Xu R-H, et al. Effect of fruquintinib vs placebo on overall survival in patients with previously treated metastatic colorectal cancer: the FRESCO randomized clinical trial. JAMA. 2018;319(24):2486-2496. doi:10.1001/jama.2018.7855
  4. A study of efficacy and safety of fruquintinib (HMPL-013) in patients with metastatic colorectal cancer (FRESCO-2). Updated September 14, 2020. Accessed November 24, 2020.