Trials demonstrate drug efficacy for colorectal cancer

HUTCHMED (China) Limited and Takeda have announced the results of their phase III FRESCO‑2 study evaluating fruquintinib in patients with previously treated metastatic colorectal cancer (CRC), published in The Lancet.

Fruquintinib is a highly selective and potent vascular endothelial growth factor receptor (VEGFR) -1, -2 and -3 inhibitor. FRESCO-2 is a global multi-regional phase III clinical trial (MRCT) conducted in the US, Europe, Japan and Australia investigating fruquintinib plus best supportive care (BSC) vs placebo plus BSC in patients with previously treated metastatic CRC.

The FRESCO-2 study met its primary primary and secondary endpoints, demonstrating that treatment with fruquintinib resulted in statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS), respectively. The safety profile of fruquintinib in FRESCO-2 is consistent with previously reported fruquintinib studies.

FRESCO-2 is a major study supporting a regulatory filing to the US Food and Drug Administration (FDA) for fruquintinib for the treatment of previously treated metastatic CRC, which was accepted for review and given Priority Review in May 2023. Submission of a Marketing Authorization Application (MAA) to European Medicines Agency (EMA) and NDA to Japan Pharmaceuticals and Medical Devices Agency (PMDA) planned for 2023.

In March 2023, HUTCHMED and Takeda concluded an exclusive licensing agreement to advance the global development, commercialization, and manufacture of fruquintinib outside of China.

About CRC

CRC is cancer that starts in the colon or rectum. According to the International Agency for Research on Cancer, CRC is the third most common cancer worldwide, linked to more than 935,000 deaths in 2020. In the US, an estimated 153,000 patients will be diagnosed with CRC and 53,000 deaths from this disease will occur in 2023.

In Europe, CRC is the second most common cancer in 2020, with around 520,000 new cases and 245,000 deaths. In Japan, CRC is the most common cancer, with an estimated 148,000 new cases and 60,000 deaths by 2020. Although early-stage CRC can be resected surgically, metastatic CRC remains an area of ​​high unmet need with poor outcomes and limited treatment options. limited. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, the majority of patients have tumors that do not have actionable mutations.

About fruquintinib

Fruquintinib is a highly selective and potent oral inhibitor of 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 approval in CRC in China

Fruquintinib was approved for marketing by the China National Medical Products Administration (NMPA) in September 2018 and was launched commercially in China in November 2018 under the brand name ELUNATE. It has been included in China’s National Reimbursement Drug List (NRDL) since January 2020. ELUNATE is indicated for the treatment of patients with metastatic CRC who have previously been treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-VEGF therapy. -EGFR (wild-type RAS). Approval in China is supported by the results of the FRESCO study, a landmark phase III registration trial of fruquintinib in 416 patients with metastatic CRC in China.

HUTCHMED is marketing fruquintinib in China in partnership with Eli Lilly and Company.

The safety and efficacy of fruquintinib for investigative use has not been established and there is no guarantee that it will receive health authority approval or be commercially available in any country for the use under investigation.

Phase III FRESCO-2 trial outside China

The FRESCO-2 study was a multi-regional clinical trial conducted in the US, Europe, Japan and Australia investigating fruquintinib plus BSC vs placebo plus BSC in patients with previously treated metastatic CRC. These studies fulfilled the main primary and secondary endpoints, demonstrating that treatment with fruquintinib resulted in statistically significant and clinically significant improvements in OS and PFS, respectively.

The median OS was 7.4 months for 461 patients treated with fruquintinib compared with 4.8 months for 230 patients in the placebo group. The mean PFS was 3.7 months for patients treated with fruquintinib compared with 1.8 months for patients in the placebo group. The rate of disease control (DCR) was 56% in the fruquintinib group compared to 16% for patients in the placebo group. The median duration of follow-up was approximately 11 months for patients in both groups.

The safety profile of fruquintinib in FRESCO-2 is consistent with previously reported fruquintinib studies. Adverse events grade 3 or higher occurred in 63% of patients receiving fruquintinib plus BSC, compared with 50% of patients receiving placebo plus BSC. Grade 3 or higher adverse events that occurred in ≥ 5% of patients receiving fruquintinib were hypertension (14% vs 1% in the placebo group), asthenia (8% vs 4% in the placebo group) and hand-foot syndrome (6% vs 0% in the placebo group). Side effects leading to discontinuation occurred in 20% of patients receiving fruquintinib, compared with 21% of patients receiving placebo.

More fruquintinib news

Stomach Cancer in China: The FRUTIGA Study was a randomized, double-blind, phase III study in China to evaluate fruquintinib in combination with paclitaxel versus paclitaxel monotherapy, for second-line treatment of advanced gastric cancer or gastroesophageal junctional adenocarcinoma. Topline results to be announced in November 2022. The trial met one of the key endpoints of statistically significant, clinically significant increase in PFS. The other major OS endpoints were not statistically significant per pre-specified statistical plan, despite a numerical increase in the OS median.

Fruquintinib also showed statistically significant improvements in secondary end points including objective response rate (ORR), DCR, and increased response duration (DoR). The safety profile of fruquintinib in FRUTIGA is consistent with previously reported studies. Full detailed results are expected to be disclosed at a future scientific meeting.

HUTCHMED is also developing fruquintinib for the treatment of several solid tumor cancers in combination with PD-1 monoclonal antibody for the treatment of endometrial tumors and other solid tumors.

HUTCHMED has had a series of positive results for its products. In November 2022, the results of a positive stomach cancer study were announced in China. Earlier in 2022, the company, along with AstraZeneca, announced that patients in a lung cancer trial were responding well to combination treatment.