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 & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/events/conferences-snippets/asco-gi-2023-keytruda-looms-over-zanidatamabs-second