In an interim analysis of the DESTINY-Lung01 trial, trastuzumab deruxtecan (T-DXd) demonstrated clinical activity with a high objective response rate and durable response rate in patients with HER2-mutated non-small cell lung cancer (NSCLC), researchers reported at the at the virtual meeting of the American Society of Clinical Oncology.

T-DXd is a novel antibody-drug conjugate. It consists of three components: a humanized, anti-HER2 monoclonal antibody, a topoisomerase I inhibitor payload, and an exatecan derivative, linked by a tetrapeptide-based cleavable linker. T-DXd has a high drug-to-antibody ratio of approximately 8; that is, there are eight molecules attached to one monoclonal antibody.

DESTINY-Lung01 is an ongoing, multicenter, phase 2 trial of T-DXd in patients with unresectable, metastatic non-squamous NSCLC who have relapsed or are refractory to standard treatments and whose tumors overexpress HER2 or contain a HER2-activating mutation. At data cutoff, 42 patients with HER2-mutation had received T-DXd. Median treatment duration was 7.75 month (range, 0.7-14.3 months); 45.2% of the patients remained on treatment.

“Confirmed objective response rate among these 42 patients was 61.9%; one patient had a complete response, 25 patients had a partial response”, reported Egbert Smit, Professor of Pulmonary Medicine at the Netherlands Cancer Institute, Amsterdam, The Netherlands. Median duration of response was not reached at data cutoff. Estimated median progression-free survival was 14.0 months (95% CI: 6.4-14.0 months), median overall survival was not yet reached. Drug-related treatment-emergent adverse events (TEAE) grade ≥3 were observed in 22 patients (52.4%), and drug-related serious TEAE in 7 patients (16.7%). There were 5 cases (11.9%) of low-grade drug-related interstitial lung disease.

“These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated non-small cell lung cancer”, Prof. Smit concluded.


Reference:  Smit EF, et al. ASCO 2020 virtual meeting, abstract 9504