First Patient Dosed with AP402 in a Trial for HER2 Advanced Tumors

The first patient has been dosed in a phase 1/2 trial evaluating treatment with AP402, a potential first-in-class, next generation T cell engager targeting CD137 and p95HER2, for patients with relapsed/refractory anti-HER2 treatment, according to a news release from AP Biosciences.

The phase 1 AP402-101 clinical trial will take place Australia and is evaluating the safety, tolerability and preliminary efficacy of AP402 in HER2 positive patients with advanced solid tumors, including breast cancer. The dose expansion phase may include sites in Taiwan, South Korea and the United States.

“AP402 targets p95HER2, a truncated form of HER2 present in 30 to 40% of HER2-positive cancers, which is associated with exceptionally poor prognosis, and not addressable by conventional anti-HER2 therapies,” said Jeng Her, founder and chief executive officer of AP Biosciences. “AP402 represents the only T-cell engager in human trials which bridges activated T cells and p95HER2-expressing cancer cells in the tumor — a differentiated mechanism that could deliver a powerful immune response while minimizing systemic toxicity.”

AP402 combines p95HER2 targeting with a CD137 activation domain to activate T-cells specifically in the tumor microenvironment, according to the news release. This design allows clustering of HER2 variants to trigger CD137-mediated T-cell activation, minimizing side effects from systemic cytokine release.

AP402-101 is a multi-center, open-label phase 1 trial enrolling up to 85 patients in two parts: a dose-escalation phase to determine the maximum tolerated dose and recommended phase 2 dose, followed by a dose-expansion phase targeting specific HER2-positive tumor types. The primary end points are safety and tolerability, while secondary end points include objective response rate, disease control rate, and pharmacokinetic parameters. Exploratory end points will assess pharmacodynamic biomarkers and immunogenicity.

The company announced preclinical data supporting the therapeutic potential of AP402 will be presented in a poster at this year’s American Association for Cancer Research (AACR) conference.

Trial Design and HER2 Disease Explained

During part 1, dose escalation will involve seven cohorts, with an intravenous (IV) infusion of AP402 administered every two weeks to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D). The first two cohorts will use an accelerated dose titration design, followed by a standard 3 plus 3 dose titration design for the remaining five cohorts. Up to 42 patients will be enrolled in part 1.

During part 2, once the MTD and/or RP2D are determined by the safety review committee, additional patients will be enrolled in part 2 and treated with AP402 at that dose every two weeks. Part 2 is expected to enroll around 43 patients in one or two selected tumor types.

The investigational product will be administered for 12 months or until confirmed progressive disease, initiation of alternative cancer therapy, intolerable toxicity, withdrawal of consent, study completion, death or other reasons for treatment discontinuation.

The primary end points of both parts include the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary clinical activity of AP402.

HER2 is a protein involved in normal cell growth. According to the National Cancer Institute, HER2 may be produced in larger amounts by some cancer cells, including those in the breast, ovarian, bladder, pancreatic, stomach and esophagus. This overproduction can cause cancer cells to grow faster and spread. Measuring HER2 levels on certain cancer cells may help guide treatment. HER2 is also known as c-erbB-2, HER2/neu, human EGF receptor 2 and human epidermal growth factor receptor 2.

For more information visit ClinicalTrials.gov using the clinical trial ID: NCT06669975.

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