If February’s positive readout of the Clear study gave Merck & Co’s Keytruda an important lead over its rivals in front-line kidney cancer, today’s apparent win in Keynote-564 could stretch the advantage further still. Keynote-564 was the first of several pivotal immunotherapy studies to read out in this cancer’s even earlier, adjuvant setting, a market currently untapped by anti-PD-(L)1 drugs. Adjuvant and neoadjuvant settings are becoming key battlegrounds for checkpoint-blocking drugs, but kidney cancer is somewhat under the radar. Nevertheless, all the big players are running phase 3 trials. Merck has said nothing about the magnitude of Keytruda’s disease-free survival win in Keynote-564, except that this is statistically and clinically significant; whether this endpoint is sufficient for approval rather than the gold standard of overall survival is up to regulators. However, bulls will note that DFS is a more robust measure than pathological complete response, the endpoint on which Merck tripped up when trying to extend Keytruda’s label to perioperative triple-negative breast cancer; that setting will require the company to wait until the Keynote-522 trial reads out for event-free survival.
|Pivotal trials of anti-PD-(L)1 drugs in adjuvant renal cell carcinoma|
|Keynote-564||Keytruda vs placebo||DFS||Said to be statistically significant & clinically meaningful for DFS|
|Immotion-010||Tecentriq vs placebo||DFS||Primary completion Jan 2022|
|Checkmate-914||Opdivo +/- Yervoy vs placebo||DFS||Primary completion Apr 2023|
|Rampart||Imfinzi +/- tremelimumab vs placebo||DFS & OS||Primary completion Jul 2024|
|Source: Mizuho & clinicaltrials.gov.|