ESMO 2023: Merck’s Welireg Demonstrates Sustained PFS Benefit in Advanced Renal Cell Carcinoma, Despite Ongoing OS Concerns

PFS Benefit:
The LITESPARK-005 trial showed that Welireg significantly improved progression-free survival (PFS) in patients with advanced renal cell carcinoma (RCC) compared to everolimus (Afinitor). The 12-month PFS rate was 33.7% for Welireg patients versus 17.6% for those on everolimus, and the 18-month PFS rate was 22.5% versus 9.0%.

OS Concerns:
Despite the PFS benefit, the overall survival (OS) data did not achieve statistical significance. The median OS for Welireg patients was 21 months compared to 17.2 months for those on everolimus. However, Merck notes that the OS data is still immature and may improve with more time.

Objective Response Rate (ORR):
Welireg demonstrated a significant improvement in ORR, with 21.9% of patients achieving an objective response compared to 3.5% for those on everolimus. Additionally, 13 Welireg patients experienced complete responses, while none were reported in the comparator arm.

Clinical Significance:
The LITESPARK-005 trial is the first Phase 3 study to show positive results in patients with advanced RCC following both immune checkpoint and anti-angiogenic therapies in later lines of treatment.

Future Directions:
Merck is discussing these results with regulatory authorities worldwide and hopes to expand the indications for Welireg, which is currently approved for the rare von Hippel-Lindau (VHL) disease.