Merck & Co.'s Welireg meets PFS goal in Phase III renal cell carcinoma study

2023-08-18

临床3期临床结果上市批准加速审批抗体药物偶联物

Merck & Co. announced Friday that Welireg (belzutifan) significantly extended progression-free survival (PFS) in a Phase III trial of patients with advanced renal cell carcinoma (RCC). The oral HIF-2α inhibitor HIF-2α inhibitor was granted an approval by the FDA in 2021 to treat cancers associated with von Hippel-Lindau disease.

The new trial, dubbed LITESPARK-005, has an estimated enrolment of 736 patients with advanced RCC that has progressed after prior PD-1/L1 and VEGF-targeted therapies. Participants were randomised to receive once-daily oral Welireg or the mTOR blocker everolimus.

According to top-line results, Merck said Welireg led to "significant and clinically meaningful improvement" on the dual primary endpoint of PFS based on a pre-specified interim analysis. The company also reported that a "trend toward improvement" was seen on the other main goal of overall survival (OS), but did not reach statistical significance, adding that OS would be tested at a future analysis. Meanwhile, there was a significant improvement on the key secondary endpoint of objective response rate (ORR), Merck said.

The company noted that Welireg's safety profile in the trial was consistent with previously reported studies. The drug's current label for cancers linked to von Hippel-Lindau disease carries a boxed warning about embryo-foetal toxicities. Merck plans to share the LITESPARK-005 results at an upcoming medical meeting.

Marjorie Green, head of late-stage oncology at Merck Research Laboratories, said there is a need for new treatment options for advanced RCC patients who have progressed following PD-1/L1 and VEGF-TKI therapies. "This is the first Phase III trial to show positive results in advanced RCC following these therapies and the first new mechanism to demonstrate potential in advanced RCC in recent years," she said, adding "we look forward to discussing these results with health authorities."

Prior to Friday's readout, one key opinion leader (KOL) interviewed for a FirstWord report on RCC had predicted that LITESPARK-005 was likely to be positive, "more so because the control agent is not effective," noting that the trial, however, "doesn't answer the question that's more important – which is comparison to other more potent TKIs. Getting a drug approved has nothing to do with people using it." Meanwhile, another KOL suggested that an OS benefit would be crucial to ensure uptake of Welireg, adding "if it's just PFS which is positive, it's not going to be very convincing for people."

Three other Phase III trials that comprise Welireg's development programme in RCC include LITESPARK-011 and LITESPARK-012, which are evaluating the drug in second-line and treatment-naïve settings, as well as LITESPARK-022 testing it in combination with Keytruda (pembrolizumab) in the adjuvant setting.

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