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.

Filling in the blanks in 1st-line Her2+ GEA 
  Zanidatamab + chemo (ph2, n=42)  Keytruda + Herceptin + chemo (Keynote-811)** Herceptin + chemo (Toga trial)
mOS  not reached* ? 13.8 months
mPFS 12.5 months ? 6.7 months
ORR  79% (CR~8%) 74% (CR=11%) 47%
mDOR  20.4 months 10.6 months 6.9 months
18-mth OS 84% - -
12-mth OS  88% - -
Notes: *median duration of study follow-up 26.5 months; **first interim analysis when the first 260 pts enrolled had ≥8.5 mo of follow-up, tested ORR. Source: Asco publications, company communications &

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