Keytruda’s liver success again raises the Asia question

Can a study conducted in Asian patients serve as the basis for a US approval? This is the question the FDA will answer when it reviews Keynote-394, a trial of Merck & Co’s Keytruda in Chinese, Malaysian, South Korean and Taiwanese liver cancer patients that was yesterday toplined positive. An affirmative answer would spell good news for Coherus, for instance, a company that will hope to challenge Keytruda’s US dominance in front-line lung cancer on the basis of a trial run exclusively in China. Some years ago Richard Pazdur, director of the FDA’s oncology division, courted Chinese companies with promises that China-only trials might suffice, and last month a separate company, Beyondspring, claimed to have been told by the FDA that this was possible as long as pharmacokinetic data for US and Asia patients were similar. Merck says that in Keynote-394 Keytruda beat placebo in extending overall survival of liver cancer patients who had failed Nexavar, and the result could formalise Keytruda’s accelerated approval in this setting. This approval risked being rescinded after the failure of Keynote-240, but an adcom’s decision to retain it, largely because Keynote-394 had yet to read out, could now be vindicated.

Anti-PD-(L)1 drugs with accelerated US approvals and failed confirmatory trials
Indication Failed potentially confirmatory trial(s) 27-29 Apr 2021 adcom vote Regulatory outcome Advanced potentially confirmatory trials remaining?
Keytruda (Merck & Co)
Urothelial bladder cancer (2L/1L) Keynote-361 (1L) Keep indication (5-3) US label narrowed 3 Jul 2018 & 31 Aug 2021 Keynote-676 (BCG combo in non-muscle invasive bladder cancer)
Liver cancer (2L) Keynote-240 (2L) Keep indication (8-0) None Keynote-394 (2nd-line Asian patients)*
Gastric/GEJ adenocarcinoma (3L) Keynote-061 (2L) & 062 (1L, inconclusive) Withdraw (6-2) Withdrawn 1 Jul 2021 Keynote-585 (neoadjuvant/adjuvant chemo combo)
SCLC (3L) Keynote-604 (1L) (NA - already withdrawn) Withdrawn 1 Mar 2021 No
Tecentriq (Roche)
Urothelial bladder cancer (1L) Imvigor-211 (2L) Keep indication (10-1) US label narrowed 3 Jul 2018; 2L use withdrawn 8 Mar 2021 Imvigor-130 final readout
TNBC (1L) Impassion-131 (1L) Keep indication (7-2) Withdrawn 27 Aug 2021 Impassion-132 (note OS benefit in Ipassion-130 not statistically tested)
Opdivo (Bristol Myers Squibb)
Liver cancer (2L) Checkmate-459 (1L) Withdraw (5-4) Withdrawn 23 Jul 2021 Checkmate-9DX (adjuvant)
SCLC (3L) Checkmate-331 (2L) & 451 (1L) (NA - already withdrawn) Withdrawn 29 Dec 2020 No
Imfinzi (Astrazeneca)
Urothelial bladder cancer (2L) Danube (1L, tremelimumab combo) (NA - already withdrawn) Withdrawn 22 Feb 2021 Nile (tremelimumab combo)
Note: *toplined positive on 27 Sep 2021. Source: company information.

Related Topics

Share This Article