Posted: Friday, January 28, 2022
Pasi A. Jänne, MD, PhD, of the Dana-Farber Cancer Institute, Boston, and colleagues evaluated the safety and efficacy of patritumab deruxtecan—an antibody–drug conjugate consisting of a HER3 antibody (HER3-DXd)—in EGFR inhibitor–resistant, EGFR-mutated non–small cell lung cancer (NSCLC). Published in Cancer Discovery, the results of their study showed that HER3-DXd demonstrated clinical activity among known and unknown EGFR tyrosine kinase–resistant mechanisms, suggesting it may be of future use as a treatment option for patients with this type of lung cancer.
This phase I, open-label study enrolled 81 patients with locally advanced or metastatic, EGFR inhibitor–resistant, EGFR-mutated NSCLC. Participants were administered 3.2 to 6.4 mg/kg of HER3-DXd intravenously on day 1 of each 21-day cycle (n = 36). The dose-expansion cohort (n = 45) received the recommended dose for escalation (5.6 mg/kg) as either a frozen liquid or a lyophilized drug product.
The median treatment duration was 5.5 months, and a total of 57 patients received HER3-DXd at 5.6 mg/kg. The median number of prior therapy lines was four, and all patients previously received an EGFR tyrosine kinase inhibitor; resistance to these inhibitors was identified in 78% of participants.
Treatment-emergent adverse events were reported in all patients, with the most common being nausea (60%) and fatigue (64%). Events of grade 3 or higher, such as thrombocytopenia (26%), neutropenia (15%), and fatigue (10%), were reported in 64% of individuals.
The median progression-free survival was 8.2 months. The confirmed objective response rate was 39%, and confirmed responses occurred at a similar frequency among subgroups regardless of prior tyrosine kinase inhibitor; those who did not receive chemotherapy had an objective response rate of 63% and a median progression-free survival of 7.6 months. Of note, patients defined as having early clearance of circulating tumor DNA exhibited a higher response rate (68% vs. 19%) and longer progression-free survival (8.3 vs. 4.4 months) than those who did not.
Disclosure: For full disclosures of the study authors, visit cancerdiscovery.aacrjournals.org.