An antibody fused to a targeted drug has produced impressive results in a Phase I clinical trial involving patients with advanced non-small cell lung cancer (NSCLC) whose tumours had become resistant to a standard targeted therapy. Dana-Farber's Pasi A. Jänne, MD, PhD, is lead author of the study.

The trial evaluated the safety and effectiveness of patritumab deruxtecan, an antibody drug conjugate consisting of an antibody targeting the protein HER3 and an inhibitor of the topoisomerase 1 enzyme, in 57 patients whose NSCLC carried an EGFR gene mutation but no longer responded to EGFR-targeting drugs.

Patients who become resistant to such drugs and to platinum-based chemotherapy usually have few treatment options.

After a median treatment time of 5.5 months, 39% of the participants had a confirmed clinical response to the conjugate, a reduction in tumour size or extent.

Among these patients, the median progression-free survival was 8.2 months. The antitumour effect occurred in patients whose resistance to EGFR inhibitors arose from a range of molecular mechanisms and in those with no clear identifiable resistance mechanism.

The most common severe side effects were decreased blood platelet counts, lowered counts of neutrophils (a type of white blood cell), and fatigue, all consistent with previous safety studies.

The results have prompted investigators to open a Phase 2 trial of the conjugate for patients with EGFR-mutant NSCLC whose disease has become resistant to EGFR-targeting drugs and chemotherapy.

Source: Dana-Farber Cancer Institute