MSD Japan Files for Welireg and Keytruda Combination Therapy as Adjuvant RCC Treatment – MSD Japan

MSD Inc., Tokyo (known as Merck Inc in the USA and Canada) announced that for the Welireg (belzutifan), Merck’s first-in-class oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor in combination with the anti-PD-1 antibody Keytruda (pembrolizumab) a submission has been made for a partial amendment to the manufacturing and marketing approval as a postoperative adjuvant therapy for renal cell carcinoma after nephrectomy.

This partial change application for manufacturing and marketing approval is intended for patients with pale clear-cell renal cell type renal cell carcinoma (ccRCC) who have intermediate~high or high risk of recurrence after nephrectomy, or M1 NED (M1 no evidence of disease), and will be treated as adjuvant therapy after nephrectomy using Welileg and Keytruda. This is based on data from LITESPARK-022, a multicenter, randomized double-blind phase 3 trial comparing combination therapy with placebo + Keytruda.

LITESPARK-022 enrolled 1,841 patients and demonstrated that Keytruda in combination with Welireg significantly improved disease-free survival (DFS), the trial’s primary endpoint, reducing the risk of disease recurrence, metastasis or death by 28% (HR=0.72 [95% CI 0.59-0.87]; p=0.0003) for patients with ccRCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions compared to Keytruda plus placebo. The estimated 24-month DFS rate was 81% (95% CI 0.78-0.83) with Keytruda plus Welireg compared to 74% (95% CI 0.71-0.77) with Keytruda plus placebo. Median DFS was not reached in either arm. Overall survival (OS) results were not yet mature at this interim analysis.

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for about 90% of all cases. In Japan, about 21,000 new cases of kidney cancer (excluding renal pelvis cancer) were newly diagnosed in 2019. In patients with RCC with a high risk of recurrence after nephrectomy, new treatment options to suppress recurrence are needed.