Hutchmed: Treating Advanced Refractory Metastatic Colorectal Cancer
On August 8, 2022, Hutchmed (HCM) announced that pivotal global Phase 3 FRESCO-2 trial evaluating the investigational use of fruquintinib met its primary endpoint of overall survival (OS) in patients with advanced, refractory metastatic colorectal cancer (CRC).
The FRESCO-2 Study
A multi-regional clinical trial conducted in the U.S., Europe, Japan and Australia demonstrates that investigated fruquintinib plus best supportive care vs placebo plus BSC in patients with metastatic CRC that had progressed on standard chemotherapy and relevant biologic agents, and had progressed on, or were intolerant to, TAS-102 and/or regorafenib.
In addition to the OS, a statistically significant improvement in progression-free survival (PFS), which is a key secondary endpoint has been observed.
The safety profile of fruquintinib in FRESCO-2 was consistent with previously reported studies.
Hutchmed has been in communication with regulatory agencies globally regarding the FRESCO-2 trial design and conduct and will discuss these data with the agencies in the U.S., Europe, and Japan with the intent to submit marketing authorization applications as soon as possible.
In June 2020, the U.S. FDA granted Fast Track Designation for the development of fruquintinib for patients with metastatic CRC.
From Hutchmed and Others
Dr Marek Kania, Executive Vice President, Managing Director and Chief Medical Officer of Hutchmed International, said, “We are very happy to see the positive outcomes of the FRESCO-2 study which offers a potential new treatment for patients with advanced metastatic colorectal cancer, where there is a very high unmet need and limited treatment options. Results from the global FRESCO-2 study supplement findings from the original FRESCO study that led to the marketing approval and commercialization of fruquintinib in China. …..”
Professor Cathy Eng, MD, FACP, FASCO, David H. Johnson Endowed Chair in Surgical and Medical Oncology and Co-Leader, Gastrointestinal Cancer Research Program, at the Vanderbilt-Ingram Cancer Center who served as the FRESCO2 co-PI and Steering Committee member, said, “Completion of the international FRESCO-2 phase III trial in a timely fashion during the era of COVID-19 isolation demonstrates the unmet need for new therapeutic agents in metastatic colorectal cancer. By meeting the primary endpoint of OS with a secondary endpoint of PFS, fruquintinib provides a significant potential new option for our refractory colorectal cancer patients. As oral agent, fruquintinib provides added convenience for our patients. Based on fruquintinib’s profile, we will likely see further exploration in future clinical trials in different settings. This is extremely encouraging, and I look forward to seeing the final results.”
Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of Hutchmed, said, “We are pleased to have successfully completed our first multi-regional clinical trial, FRESCO-2, to support the global registration of fruquintinib. It has already benefited patients with advanced CRC in China since its launch in 2018. It is also being evaluated alone and in combination with other agents in various tumor types in ongoing studies around the world.”
Hutchmed retains all commercial rights to fruquintinib outside of China. In China, where fruquintinib is marketed under the brand name ELUNATE®, HUTCHMED is partnered with Eli Lilly and Company. It is responsible for development and execution of all on-the-ground medical detailing, promotion and local and regional marketing.
Fruquintinib is not approved for use outside of China.
The Drug, Fruquintinib
Fruquintinib is a highly selective and potent oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.
Fruquintinib Approval in China
Fruquintinib was approved for marketing by the China National Medical Products Administration (NMPA). The product is launched in China under the name ELUNATE®. The product is indicated for metastatic CRC in patients that have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type).
Results of the FRESCO Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).
The FRUTIGA study
FRUTIGA Trial is a randomized, double-blind, Phase III trial evaluating the efficacy and safety of fruquintinib + paclitaxel for the treatment of patients with advanced gastric or esophagogastric junction (GEJ) adenocarcinoma who did not respond to first-line standard chemotherapy. Approximately 700 patients have received either fruquintinib combined with paclitaxel or placebo combined with paclitaxel.
The co-primary efficacy endpoints are OS and PFS (clinicaltrials.gov identifier: NCT03223376).
Hutchmed has entered into collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317, developed byBeiGene, Ltd) and sintilimab (IBI308) developed by Innovent Biologics, Inc. and marketed as TYVYT® in China).
Metastatic breast, endometrial, and colorectal cancers in the U.S.
Hutchmed initiated this open-label, multi-center, non-randomized, Phase Ib/II study in the U.S. to investigate if the addition of fruquintinib can potentially induce activity to immune checkpoint inhibitor therapy in advanced, refractory triple negative breast cancer (TNBC), endometrial cancer, and CRC.
Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04577963. Safety and preliminary efficacy of fruquintinib as a single agent were demonstrated in advanced solid tumors, including TNBC, in a Phase I study conducted in China (NCT01645215) and a Phase I/Ib study is ongoing in the U.S. (NCT03251378).
Gastric,Ccolorectal and Non-Small Cell Lung Cancers in China & Korea
BelGene Ltd. initiated this open-label, multi-center, Phase II study to assess the safety and efficacy of fruquintinib + tislelizumab in patients with advanced or metastatic, unresectable GC, CRC or non-small cell lung cancer (NSCLC).
Endometrial Cancer and Other Solid Tumors in China
Hutchmed initiated open-label, multi-center, non-randomized, Phase II study to assess the safety and efficacy of fruquintinib + sintilimab in patients with advanced cervical cancer, endometrial cancer, GC, hepatocellular carcinoma (HCC), NSCLC or renal cell carcinoma.
Preliminary results of certain cohorts were presented at the 2021 American Society of Clinical Oncology Annual Meeting (ASCO) and the Chinese Society of Clinical Oncology Annual Meeting (CSCO). Following encouraging data in the advanced endometrial cancer cohort, it has been expanded into a single arm registrational Phase II study of over 130 patients. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT03903705.
Hutchmed is commercial-stage, biopharmaceutical company. It discovers and globally develop and commercialize targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has more than 4,900 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception it has advanced 13 cancer drug candidates from in-house discovery into clinical studies around the world, with its first three oncology drugs now approved and marketed in China.
Metastatic CRC is a killer. It starts in either the colon or rectum. CRC is the third most common cancer worldwide. In the U.S., in 2020, CRC is estimated to have caused more than 915,000 deaths, in 2022 an estimated 151,000 people will have been diagnosed with CRC and 53,000 people will have died. In Europe, metastatic colorectal cancer is the second most common cancer, with an estimated 507,000 new cases and 240,000 deaths in 2020. In Japan, CRC is the most common cancer, with an estimated 147,000 new cases and 59,000 deaths in 2020.
Bottom line, we need products that will bring results to patients living with metastatic CRC who have lost hope, as well as other cancers with unmet needs.
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