MSD Launches Two International Multicenter Phase 3 Trials of Belzutifan in China for Renal Cell Carcinoma

Recently, the official website of the Chinese Drug Clinical Trial Registration and Information Disclosure Platform showed that MSD has launched two Phase 3 international multicenter clinical trials in China for the new anti-tumor drug belzutifan tablets. These trials target first-line treatment for advanced clear cell renal cell carcinoma (ccRCC) and adjuvant treatment for renal cell carcinoma (RCC). Public information indicates that belzutifan (MK-6482) is the first hypoxia-inducible factor (HIF-2α) inhibitor approved by the U.S. FDA. It received FDA approval for marketing in August 2021 to treat von Hippel-Lindau (VHL) disease-related cancers. Notably, research targeting the HIF-2α signaling pathway won the Nobel Prize in Physiology or Medicine in 2019.

Screenshot source: Drug Clinical Trial Registration and Information Disclosure Platform

Belzutifan is an investigational, novel, potent, and selective oral HIF-2α inhibitor currently being evaluated in multiple clinical trials for the treatment of VHL-associated renal cell carcinoma, advanced renal cell carcinoma, and other advanced solid tumors. VHL is a tumor suppressor protein, the inactivation of which can abnormally activate the HIF-2α protein in cancer patients. The HIF-2α factor can accumulate in patients, leading to the formation of benign and malignant tumors. Based on the positive results achieved by belzutifan in clinical trials, the FDA has granted this product Breakthrough Therapy Designation and Orphan Drug Status.

According to the Chinese Clinical Trial Registry and Information Disclosure Platform, MSD has recently launched two Phase 3 clinical trials in China. One of the trials will compare the efficacy and safety of pembrolizumab combined with belzutifan and lenvatinib, or MK-1308A combined with lenvatinib, versus pembrolizumab combined with lenvatinib as a first-line treatment in subjects with advanced clear cell renal carcinoma. The primary endpoint of this trial is progression-free survival (PFS) and overall survival (OS), while the secondary endpoints include objective response rate (ORR), duration of response (DOR), adverse events (AE), and discontinuation due to AE. The principal investigator of this study is Dr. Guo Jun from Beijing Cancer Hospital, with plans to enroll 216 participants in China and 1,431 participants internationally.

Another trial will evaluate the efficacy and safety of belzutifan in combination with pembrolizumab versus placebo in combination with pembrolizumab as adjuvant treatment in subjects with clear cell renal cell carcinoma post-nephrectomy. The primary endpoint of this trial is investigator-assessed disease-free survival (DFS), and the secondary endpoints include overall survival of the subjects, adverse events (AEs), AEs leading to discontinuation of study treatment, and investigator-assessed disease recurrence-specific survival (DRSS), among others. The principal investigator of this study is Dr. Dingwei Ye from Fudan University Shanghai Cancer Center, with plans to enroll 240 participants in China and 1600 participants internationally.

Previously, belzutifan achieved positive results in a Phase 2 clinical trial for the treatment of patients with renal cell carcinoma associated with VHL disease, which were published in The New England Journal of Medicine. The results showed that out of 61 patients with renal cell carcinoma who received treatment, 30 (49%) achieved partial response, and another 30 patients (49%) had stable disease. Reduction in tumor lesions was observed in 92% of the patients. At 24 months, the progression-free survival rate was 95%. As of the data cutoff date, 89% of the patients were still undergoing treatment.

Clear cell renal cell carcinoma is a common type of renal cell carcinoma, accounting for approximately 70% of all renal cell carcinoma cases. For patients with advanced clear cell renal cell carcinoma, first-line treatment options include PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors or vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (TKI). However, about 20% to 30% of renal cell carcinoma patients are diagnosed with metastatic tumors, and some patients eventually experience disease progression despite receiving treatment, indicating a less optimistic treatment outlook for these patients.

References:

[1] Official Website of China Drug Clinical Trial Registration and Information Disclosure Platform. from http://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml

[2] FDA approves belzutifan for cancers associated with von Hippel-Lindau disease. Retrieved August 13, 2021, from https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-belzutifan-cancers-associated-von-hippel-lindau-disease

[3] Jonasch et al., (2021). Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau Disease. NEJM, DOI: 10.1056/NEJMoa2103425

▽Follow [@WuXiAppTec](https://twitter.com/WuXiAppTec)Germany】WeChat Official Account