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ASCO 2025: HER3-targeted antibody-drug conjugate (ADC) shows promise for treatment-resistant solid tumors

30 May 2025
ASCO 2025: HER3-targeted antibody-drug conjugate (ADC) shows promise for treatment-resistant solid tumors

A new targeted cancer drug, DB-1310, is showing early signs of effectiveness in patients with advanced solid tumours that have not responded to standard treatments, particularly those with EGFR-mutant non-small cell lung cancer (NSCLC).

This is according to results from an international clinical trial led by Dr. Aaron Lisberg at the UCLA Health Jonsson Comprehensive Cancer Centre preented at the annual American Society of Clinical Oncology meeting .

Among the patients in the trial with EGFR-mutated NSCLC, 44% saw significant shrinkage in their tumours and the drug delayed cancer growth for a median of seven months leading to a very encouraging median overall survival of 18.9 months.

Across all cancer types in the trial, 31% of patients responded to the treatment, with an average of 5.5 months before the cancer progressed and a median overall survival of 14.4 months.

The side effects of DB-1310 were generally manageable with the most common side effects being low blood counts and nausea.

“On this Phase 1/2a trial, DB-1310 has shown real potential as a new treatment option for patients with advanced solid tumours that have progressed after standard therapies,” said first author of the abstract Dr. Aaron Lisberg, assistant professor of medicine and thoracic medical oncologist at the David Geffen School of Medicine at UCLA.

“These were patients who were heavily pretreated and whose cancers had become resistant to FDA-approved treatments, yet DB-1310 offered a meaningful extension of life with a very tolerable side effect profile.”

DB-1310 is an antibody-drug conjugate (ADC), a type of therapy designed to deliver a powerful chemotherapy drug directly to cancer cells while minimising damage to healthy tissue.

The drug combines a lab-engineered antibody that recognises HER3, which is a protein commonly found on the surface of cancer cells, with a powerful cancer-killing agent.

By leveraging direct delivery of the chemotherapy payload to cancer cells, DB-1310 aims to improve treatment precision and reduce side effects associated with traditional chemotherapy.

Study enrollment remains ongoing, but at the time of data cut-off, 172 patients with advanced solid tumours who had already gone through multiple rounds of standard treatments, such as chemotherapy and targeted therapy, were treated with DB-1310.

Among these patients, 108 had NSCLC, 62 of whom had EGFR-mutant NSCLC, and 24 were patients with brain metastases.

In the Phase 1 portion of this first-in-human trial, which remains ongoing, the researchers are evaluating the intravenous administration of DB-1310 every 3 weeks at different dose levels to identify the safest and most effective dose.

The Phase 2 portion will evaluate additional patients with tumour types of interest to assess the drug’s effectiveness in treating various cancers.

The researchers say the study's findings are encouraging, particularly for patients with EGFR-mutant lung cancer, who face limited treatment options after standard therapies fail.

Larger studies are needed to confirm the results, but this early data suggests DB-1310 could potentially be a new treatment approach for patients with advanced solid tumours.

Source: University of California - Los Angeles Health Sciences