Asco-GI 2023 – Keytruda looms over zanidatamab's second shot

Zanidatamab looked good enough in Her2-amplified biliary tract cancers to persuade Jazz to part with $375m up front for the asset, but developing data in gastroesophageal adenocarcinoma must have helped seal the deal. The latest phase 2 update shows improvement on a prior cut presented at Esmo 2021, with the dual Her2 bispecific plus chemo generating an impressive 79% objective response rate. The data, which are still early, are tracking ahead of standard-of-care Herceptin plus chemo, and look at least as good as Keytruda/Herceptin/chemo in Keynote-811, a trial that won the triplet accelerated approval in 2021. This Keytruda combo generated results considered surprising, because the addition of PD-(L)1 blockade to Her2-targeting had not previously yielded much success. Could zanidatamab responses be improved by adding checkpoint inhibition? That question is being asked in the pivotal Herizon-GEA-01 trial, which reads out in 2024. Keytruda remains a threat, however, with full results from Keynote-811 expected any time. That result will provide the bar for Jazz and Zymeworks to beat, and given its burdensome diarrhoea side effect zanidatamab needs to impress to have a real chance to compete against the Merck machine.