First-in-Human Trial of Anti-AXL Antibody-Drug Conjugate in Advanced Lung Cancer
Posted: Thursday, October 17, 2019
“Encouraging” antitumor results in a phase I trial of the antibody–drug conjugate enapotamab vedotin led to a phase IIa expansion trial of patients with heavily pretreated, advanced non–small cell lung cancer. Enapotamab vedotin consists of anti-AXL human immunoglobulin G1 and monomethyl auristatin E, and it demonstrated potent antitumor activity in preclinical models, according to the initial phase IIa results presented at the International Association for the Study of Lung Cancer 2019 World Conference on Lung Cancer (WCLC) in Barcelona (Abstract OA02.05).
AXL, a transmembrane receptor tyrosine kinase, “is aberrantly expressed in various cancers and associated with poor prognosis and treatment resistance,” especially resistance to PD-1 immune checkpoint inhibitors, explained study author Suresh Ramalingam, MD, of Emory Winship Cancer Institute in Atlanta, and colleagues.
The 26 patients (median age, 65.5 years) had no sensitizing EGFR mutations or ALK rearrangements; all had failed to respond to four or more previous lines of therapy, including a PD-1/PD-L1 inhibitor, and most had a performance status of 1. They received enapotamab vedotin at 2.2 mg/kg once every 3 weeks. The trial’s endpoints included objective response rate and safety.
At a median follow-up of 18 weeks, the confirmed objective response rate was 19%, with a disease control rate of 50%. Although grade ≥ 3 treatment-emergent adverse events (most gastrointestinal) occurred in 12 patients, just 2 patients required a dose reduction.
This is a “high unmet-need patient population,” explained Dr. Ramalingam and his co-investigators. With enapotamab vedotin’s manageable safety profile, they have expanded the cohort to allow up to 60 patients “to gain further knowledge of AXL as a potential biomarker for responsiveness to enapotamab vedotin and to gather additional data on safety and efficacy.”
Disclosure: The study authors’ disclosure information may be found at wclc2019.iaslc.org.