Dr Wermke on the Investigation of BI 764532 in DLL3+ SCLC and NEC

Martin Wermke, MD, head, the Early Clinical Trial Unit, the National Center for Tumor Diseases Dresden, the University Hospital Carl Gustav Carus Dresden, the Technical University of Dresden, discusses the investigation of BI 764532 in patients with DLL3-positive small cell lung cancer (SCLC) and neuroendocrine carcinoma (NEC).

At the 2023 ASCO Annual Meeting, Wermke and colleagues presented data on the use of the novel DLL3-targeting T-cell engager in a phase 1 trial (NCT04429087), where data showed BI 764532 elicited tumor shrinkage across all tumor types., and patients treated with BI 764532 at doses of 90 μg/kg and higher (n = 71) achieved an overall response rate (ORR) of 25% and a disease control rate (DCR) of 52%. Although the maximum tolerated dose was not reached, 5 dose-limiting toxicities (DLTs) were reported, including grade 3/4 cytokine release syndrome (CRS; n = 2), grade 3 confusional state (n = 1), grade 2 infusion-related reaction (n = 1), and grade 3 nervous system disorder (n = 1). However, all DLTs were reversible, and all patients recovered.

A total of 107 patients were treated in the dose-escalation portion of the study, Wermke says. Dosing began at once every 3 weeks, then continued to a weekly regimen, with the goal of reducing the incidence of CRS, he adds.

The observed responses do not appear to be restricted to a specific tumor type, he continues, noting that investigators have seen durability in the responses thus far. At the time of the data cutoff, 14 out of 18 responders were ongoing, and some patients have been in response for at least one year, Wermke concludes.