Year in Review: Clinical Investigator Perspectives on the Most Relevant New Datasets and Advances in Gastroesophageal Cancers | Faculty Presentation 2: Other Available Therapeutic Approaches — Kohei Shitara, MD<br>CME information and select publications

Gastroesophageal Cancers | Kohei Shitara, MD

Research To Practice | Oncology Videos

Thank you again for the opportunity to join this. This is my first time participating in this session. So, this is our agenda. I organized this into three parts. First topic is HER2-positive trials, including Horizon GA and Destiny series.

And the second pillar is Clodin 18.2 targeted treatment, where I will start to establish the Zorobitaximab-containing regimen. Then I will finish a brief new treatment for esophageal scramus cancers. So, before that, this is a resistant mechanism for existing HER2-targeted agent in gastric cancers.

Intertumoral heterogeneity of HER2 is one of the problems in gastric cancer, which is more common compared with breast cancer. As a result, around half of patients reduced or lost HER2 expression after chemotherapy plus trastuzumab. And another important mechanism is heterodymer formation between HER2 and other families like EJ4 or HER3.

This could be also a reason for incomplete blockade of HER2 signal by currently available targeted agents like trastuzumab. So, we need to overcome this resistant mechanism with new agents. So, let me start with Horizon GA-01 trial.

This is a global phase 3 trial to test chemotherapy plus trastuzumab as a control arm and two treatment arms with zanidatamab. One is zanidatamab plus chemotherapy arm B, and the other is zanidatamab-tethelizumab plus chemotherapy arm.

As shown on the left side, zanidatamab is a vasovastric antibody which binds to two HER2 epitopes in domain 2 and domain 4, resulted in enhanced HER2 receptor clustering, internalization, and downregulation of the signal. It also induces very strong immunological reaction based on complement-dependent cytotoxicity.

So, this is a reason of the difference between this agent and previous trastuzumab. So, as shown here on the right side, more than 900 patients have been enrolled from 2021 to 2025.

Gastroesophageal Cancers | Kohei Shitara, MD

Read the full transcript

The candid version is on a podcast,
not the earnings call.

Gastroesophageal Cancers | Kohei Shitara, MD

Read the full transcript

The candid version is on a podcast, not the earnings call.

The candid version is on a podcast,
not the earnings call.