New data from the Phase 3 CLEAR trial (KEYNOTE-581/Study 307) has been published in The New England Journal of Medicine.

The results will also be simultaneously presented at the virtual 2021 Genitourinary Cancers Symposium in an oral presentation, on 13 February 2021.

The study showed that lenvatinib plus pembrolizumab, the anti-PD-1 therapy known as MSD outside the United States and Canada, as well as lenvatinib plus everolimus significantly improved progression-free survival versus sunitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

“The combination of lenvatinib plus pembrolizumab was shown to produce a statistically significantly improvement in outcomes compared to the current standard of care, in first line use for advanced renal cell carcinoma, particularly with regards to progression free survival, overall survival and objective response rates.

Lenvatinib plus everolimus also showed a significant improvement in progression free survival compared to current standard of care”, said Professor Dr Thomas Powles, The Royal Free and Barts Health NHS Trust, London, United Kingdom.

“These data show the potential of these combinations to provide patients with much-needed new treatments, in an area where effective options are limited.”

After a median follow-up of 27 months, lenvatinib plus pembrolizumab demonstrated statistically significant improvements across all efficacy endpoints, including progression-free survival (PFS), overall survival (OS) and objective response rate (ORR).

Lenvatinib plus pembrolizumab reduced the risk of disease progression or death by 61% (HR=0.39 [95% CI: 0.32-0.49]; p<0.001), with a median PFS of 23.9 months (95% CI: 20.8-27.7) versus 9.2 months (95% CI: 6.0-11.0) for patients treated with sunitinib.

Lenvatinib plus everolimus also showed statistically significant improvement in PFS and ORR endpoints versus sunitinib; the improvement for OS was not statistically significant.

Lenvatinib plus everolimus reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI: 0.53-0.80]; p<0.001), with a median PFS of 14.7 months (95% CI: 11.1-16.7) versus 9.2 months (95% CI: 6.0-11.0) for patients treated with sunitinib.

The safety profiles of both lenvatinib plus pembrolizumab and lenvatinib plus everolimus were consistent with previously reported studies.

Grade ≥3 treatment-related adverse events occurred in 71.6% of patients in the lenvatinib plus pembrolizumab arm and 73.0% of patients in the lenvatinibplus everolimus arm compared with 58.8% of patients in the sunitinib arm.

In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialisation of lenvatinib, both as monotherapy and in combination with pembrolizumab, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A.

Source: Eisai