EORTC-NCI-AACR: Investigational Anti-HER2 Therapy in HER2-Expressing Solid Tumors


Key Points

  • Six patients experienced a partial response (38%); six patients experienced stable disease (38%), with a disease control rate of 75%.
  • The median time the patients survived without their disease progressing was 6.24 months.

An antibody that binds simultaneously to two distinct regions of the HER2 receptor to block the growth of cancer cells has shown antitumor activity in a number of cancers, including those of the esophagus, stomach, and bowel. Updated results from a phase I clinical trial of the treatment, called ZW25, focusing on patients with esophageal, stomach, bowel, and several other cancers driven by HER2, were presented by Beeram et al at the 30th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (Abstract 6).

ZW25 is an antibody that can simultaneously bind two distinct regions of the HER2 receptor.

Murali Beeram, MD, MBBS, a medical oncologist and clinical investigator at the START Center for Cancer Care, said that as of October 16, a total of 24 patients—who had received several previous therapies (an average of 4) but whose disease has recurred—have been given between 1 and 10 cycles of ZW25 since joining the phase I trial, which started in September 2016.

Patients received ZW25 at either 10 mg/kg weekly or 20 mg/kg every other week. All patients had HER2-positive cancers, including gastroesophageal (10 patients), bowel (5), gallbladder (3), bile duct (1), cervix (1), endometrial (1), fallopian tube (1), adnexal skin (1), and parotid gland (1), and 8 of these patients remain in the trial.

Trial Findings

The latest results in 17 patients with responses available for evaluation showed that 13 experienced disease response. Six patients experienced a partial response (38%); six had stable disease (38%), for a disease control rate of 75%. Four patients (25%) experienced disease progression. The median time to disease progression was 6.24 months.

The most common adverse events were diarrhea and infusion reaction. All adverse events were grade 1 or 2; there were no treatment-related grade 3 or worse adverse events. 

Dr. Beeram said in a statement, "As a clinician, I am excited by the single-agent antitumour activity and tolerability we are seeing with ZW25, particularly in these patents with advanced HER2-expressing cancers that have progressed after multiple prior therapies, including HER2-targeted agents…. ZW25 has been well tolerated to date, which should allow it to be used in combination with other agents for potentially even better responses.”

He explained, "This unique design results in multiple mechanisms of action, including dual HER2 signal blockade, increased binding, and removal of HER2 protein from the cancer cell surface; it also stimulates the immune system to attack the cancer cells.”

A phase II/III study for patients with esophageal, stomach, and other cancers is planned for next year.

Disclosure: See study authors’ full disclosures at

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