Two-year follow-up of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, for second-line (2L) treatment of non-small cell lung cancer (NSCLC).

9558 Background: Bintrafusp alfa (M7824) is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. Interim analysis of a global phase 1 study (NCT02517398) found an objective response rate (ORR) of 27.5% and a manageable safety profile in patients with NSCLC who received bintrafusp alfa 1200 mg in the 2L setting; median overall survival (OS) was not reached. Here we present the longest efficacy and safety follow-up in a cohort receiving bintrafusp alfa. Methods: Patients with advanced NSCLC unselected for PD-L1 expression level who progressed after first-line standard treatment (no prior immunotherapy) were randomized to receive bintrafusp alfa 500 or 1200 mg (n = 40 each) Q2W until disease progression, unacceptable toxicity or trial withdrawal. The primary objective was best overall response (BOR) per RECIST 1.1; secondary and exploratory objectives include safety and OS, respectively. Results: As of October 15, 2019, a total of 40 patients received bintrafusp alfa at the recommended phase 2 dose of 1200 mg Q2W for a median of 17 (range, 2-136) weeks, with a median follow-up of 128 weeks; 18 patients were still alive, 3 patients had an ongoing response, and 1 patient remained on treatment. Results for the 1200 mg dose cohort showed an ORR of 27.5%, and a median duration of response of 18 months. The 18- and 24-month progression-free survival and OS rates were 18.4% and 11.0%, and 49.7% and 39.7%, respectively. Duration of response rates at 18 and 24 months were 42.4% and 21.2%, respectively. Median OS in patients with positive (≥1%) PD-L1 expression was 21.7 months; 6 of 7 patients with high (≥80% with Ab clone 73-10, which is equivalent to ≥50% with 22C3) PD-L1 expression were still alive. The overall safety profile has remained consistent since the interim analysis, with no new safety signals or deaths and 1 additional treatment-related discontinuation (blood alkaline phosphatase increased). Conclusions: After two years of follow-up, bintrafusp alfa continues to show manageable safety with durable responses and encouraging long-term survival, especially in patients with high PD-L1 expression. A study evaluating bintrafusp alfa vs pembrolizumab as first-line treatment for NSCLC is ongoing in patients with high PD-L1 expression (NCT03631706). Clinical trial information: NCT02517398 .