OA01.07 A Phase II Study of the Oral Selective AXL Inhibitor Bemcentinib with Pembrolizumab in Patients with Advanced NSCLC

Abstract

NI combination therapy. Of the 5 patients who derived clinical benefit (defined as best response of PR, or ongoing PR/SD at 6 months), 4 were T790M negative. Incidence of pneumonitis was 3.2% (n¼1, G1). Other toxicities include IDDM (n¼1), polymyositis (n¼1), hypothyroidism (n¼2), transaminitis (n¼1) and rash (n¼5). There were no G3-5 toxicities. We next interrogated the immune landscape of EGFR TKI resistant NSCLC, and examined the impact of ipilumumab-nivolumab. 4/23 (17.4%) baseline samples were GEP high (2/4 were T790M positive), with enrichment for exhausted CD8, Treg and overexpression of IDO1. Of these 4 patients, 2 derived clinical benefit to N monotherapy. In sequential biopsies before and after exposure to checkpoint inhibitors, increase in infiltrating CD8 T cells was associated with clinical benefit. Conclusion: While there were no significant toxicity concerns with combination checkpoint inhibition in TKI-resistant EGFR mutant NSCLC, durable response was not demonstrated in our study. High GEP alone did not seem to predict for response to checkpoint inhibitors in EGFR mutant NSCLC, possibly due an immunosuppressive tumor microenvironment.

Addressing CPI resistance in NSCLC: targeting TAM receptors to modulate the tumor microenvironment and future prospects

“…In cAxl-positive postchemotherapy and post-CPI patients, the clinical benefit rate was 73% and 86%, respectively. 106 Bemcentinib in combination with a PD-L1 inhibitor recently received a fast track designation from the FDA for the treatment of patients with serine/ threonine kinase 11 (STK11)-altered advanced/metastatic NSCLC without actionable mutations. 107 BA3011 is a humanized monoclonal antibody conjugate (CAB-AxL-ADC) that specifically binds to AxL in conditions similar to those found within the TME.…”