A study for potential registration of this combination in patients with advanced endometrial cancer previously treated in China has recently completed enrollment.
This is a multi-centre open label clinical study to evaluate the efficacy and safety of fruquintinib in combination with sintilimab. Entry criteria included endometrial cancer patients who experienced disease recurrence, disease progression or grade 3 or higher serious side effects with platinum-based chemotherapy treatment.
The primary endpoint was the independent review committee (IRC) assessed objective response rate (ORR), with secondary endpoints including the degree of disease control (“DCR”), progression-free survival (PFS), overall survival (OS), and pharmacokinetic assessment (PK). A total of 142 previously treated advanced endometrial cancer patients were enrolled.
The favorable outcome of this trial could lead to a submission to the NMPA in the first half of 2024 for regulatory approval in this treatment setting.
About endometrial cancer
Endometrial cancer is a type of cancer that starts in the uterus. Globally, an estimated 417,000 people were diagnosed with endometrial cancer and caused around 97,000 deaths in 2020. In China, an estimated 82,000 people were diagnosed with endometrial cancer and caused around 17,000 deaths in 2020.
Although early-stage endometrial cancer can be resected surgically, recurrent and/or metastatic endometrial cancer remains an area of high unmet need with poor outcomes and limited treatment options.
Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2 and -3. VEGFR inhibitors play an important role in blocking tumor angiogenesis. Fruquintinib was designed to increase kinase selectivity with the goals of minimizing off-target toxicity, increasing tolerability, and providing more consistent target coverage. Fruquintinib has generally been well tolerated in patients to date and is being investigated in combination with other anticancer therapies.
Fruquintinib was approved for marketing by the NMPA in September 2018 and was commercially launched in China in November 2018 under the brand name ELUNATE, for the treatment of patients with metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-epidermal growth factor receptor (EGFR) therapy (wild-type RAS). It has been included in the National Reimbursement Drug Register (NRDL) since January 2020.
The safety and efficacy of fruquintinib for the following investigative uses has not been established and there is no assurance that it will receive health authority approval or be commercially available in any country for the uses under investigation.
Submission of NDA rolling applications to the US Food and Drug Administration (FDA) was accepted and given priority review in May 2023 with the Prescription Drug User Expenses Act (PDUFA) of November 30, 2023. Submissions to the European Medicines Agency (EMA) were approved in June 2023, and submissions to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) are expected to be completed in 2023.
The NDA for NMPA was accepted in April 2023 for fruquintinib in combination with paclitaxel for the treatment of second-line advanced adenocarcinoma of the gastric or gastroesophageal junction.
HUTCMED is also developing fruquintinib in China for the treatment of several other solid tumor cancers in combination with an anti-PD-1 monoclonal antibody. Fruquintinib is licensed to Takeda Pharmaceutical Company Limited outside of China. HUTCHMED is marketing fruquintinib in China in partnership with Eli Lilly and Company.
Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an immunoglobulin G4 PD-1 monoclonal antibody co-developed by Innovent Biologics, Inc. and Eli Lilly and Company.
Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to the PD-1 molecule on the surface of T-cells, blocks the PD-1/PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in various cancer indications, including more than 10 clinical trials of registration or milestones.
In China, sintilimab has been approved for seven indications and included in the NRDL for six.