Esmo 2021 – Mahogany loses its polish for Macrogenics

Macrogenics is already struggling to justify a role for Margenza in Her2-positive breast cancer, and it seems that gastric tumours will prove no less difficult. New data in front-line gastroesophageal adenocarcinoma (GEA) at Esmo do not stack up favourably against Zymeworks’ zanidatamab – another anti-Her2 project hoping to take share from Roche’s Herceptin. In a phase 2 trial testing zanidatamab on top of three different chemotherapy regimens the bispecific antibody posted an objective response rate of 75%. Margenza, administered with Macrogenics’ anti-PD-1 MAb tretifanlimab, could only muster an ORR of 53% in module A of the phase 2/3 Mahogany trial. One caveat is that these are early data cuts, each concerning a few dozen evaluable Her2-positive patients, so the situation could shift. Still, Zymeworks’ stock rose 10% as the data boosted hopes for zanidatamab's potentially registrational phase 3 trial, which is to begin by year end. Macrogenics's shares, meanwhile, dropped 25%. Margenza’s best hope might be as a chemotherapy-free option in this setting, given the toxicity profile, according to the sellside. But Her2-positive gastric cancer is a small and crowded space, and the data need to get much better to look competitive.

Cross-trial comparison of Esmo data in 1st-line Her2-positive GEA
  Zanidatamab (n=28) Margenza* (n=40)
Objective response rate 75% 53%
   Complete responses 1 4
   Partial responses 20 17
Median duration of response 16 mth 10 mth
Median progression-free survival 12 mth 6 mth
Source: Esmo posters #1379P#1380P. Note: *combo with anti-PD-1, in PD-L1-positive patients.

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