NEW YORK – Daiichi Sankyo on Monday announced that it had dosed the first advanced colorectal cancer patient in a Phase II trial of its investigational HER3-directed DXd antibody-drug conjugate, patritumab deruxtecan (U3-1402).
The trial, which is expected to enroll 80 participants with previously treated, advanced, or metastatic colorectal cancer across the US, Europe, and Japan, will evaluate the agent's anti-tumor activity, as assessed by objective response rate. Patients must have received at least two prior lines of systemic treatment, including, chemotherapy and, if clinically indicated, anti-EGFR therapy, anti-VEGF therapy, or an immune checkpoint inhibitor.
The first part of the two-part trial will feature two cohorts and evaluate the agent in patients with varying levels of HER3 expression as determined by immunohistochemistry (IHC) staining. The first cohort will include patients with HER3 high expression — IHC scores of 3+ or 2+ — and the second cohort will include patients with HER3 low and HER3 negative expression, defined as IHC scores of 1+ or 0.
Based on the responses seen in the first part of the trial, Daiichi Sankyo may enroll additional patients in the second part of the trial, which will evaluate the agent in cohorts consisting of patients with HER3 high expression and both HER3-high and HER3-low expression, respectively.
While the study's primary aim will be to evaluate objective response rate, investigators will also assess secondary endpoints, including safety and tolerability, duration of response, progression-free survival, overall survival, and the relationship between HER3 expression and efficacy.
Patritumab deruxtecan comprises an anti-HER3 antibody attached to a topoisomerase I inhibitor payload and is designed to deliver a targeted dose of chemotherapy to cancer cells that express HER3 antigens on their surface. An estimated 83 percent of patients with colorectal cancer express HER3.
"The prognosis of patients with advanced or metastatic colorectal cancer remains poor, and there is a need to develop new treatment strategies, including targeting HER3," Gilles Gallant, Daiichi Sankyo's senior VP and global head of oncology development, said in a statement. In addition to the colorectal cancer trial, Daiichi Sankyo is also evaluating patritumab deruxtecan in several other cancer types, including breast cancer and non-small cell lung cancer.