ESMO: Zymeworks lays down marker in fight to unseat Herceptin

Herceptin’s long-lasting dominance of the gastroesophageal cancer market may be under threat. At the European Society of Medical Oncology Congress 2021, Zymeworks presented encouraging early data on its HER2‑targeted bispecific antibody—and a showdown with the incumbent is up next. 

The phase 1b/2 clinical trial enrolled 36 patients with tumors in their esophagus, stomach or the junction of the two organs to receive zanidatamab in combination with one of three chemotherapy regimens as a first-line treatment. Twenty-eight patients were deemed evaluable because they were HER2-positive and had measurable disease.  

Among the evaluable patients, there was one complete response and 20 partial responses, resulting in a response rate of 75%. The response rate was lowest in patients who received zanidatamab with the mFOLFOX6 combination chemotherapy regimen, although that cocktail was behind the one complete response, and the small numbers of subjects in each arm limit the conclusions that can be drawn. The overall response rate is up on the level seen at the previous cutoff point.

As it stands, median duration of response is 16.4 months, and median progression-free survival is 12 months. Almost two-thirds of patients were still on study as of the data cutoff. The study is ongoing and aiming to enroll 50 participants. 

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The figures compare favorably to data that supported approval of Roche’s Herceptin in patients with the cancers in 2010. Roche linked its combination to a response rate of 47%, compared to 35% in the chemotherapy control group. While that looks encouraging for Zymeworks, it remains to be seen whether zanidatamab performs as well in a larger, randomized clinical trial.

Zymeworks is now working with partner BeiGene to put zanidatamab through a randomized phase 3 trial. The trial will give zanidatamab with one of the two chemotherapy regimens tested in the phase 1/2 study. Some patients will also receive BeiGene’s Novartis-partnered PD-1 drug tislelizumab. The control group will receive Herceptin plus chemotherapy.

The inclusion of a checkpoint inhibitor in the phase 3 follows the approval of Keytruda as a first-line treatment, in combination with Herceptin, for locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction cancers. Merck secured the approval after linking Keytruda to a response rate of 74% versus 52% in the control group.