KEY TAKEAWAYS
- The Phase I trial aimed to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion of BI 764532 in patients with locally advanced/metastatic DLL3-positive tumors.
- BI 764532 demonstrated promising efficacy and safety in patients with LCNEC.
Delta-like ligand 3 (DLL3) is a protein expressed on many cancers, including large cell neuroendocrine carcinoma of the lung (LCNEC). LCNEC has a poor prognosis, with a 5-year survival rate of approximately 5%, highlighting the need for effective treatments. BI 764532 is a DLL3/CD3 IgG-like T-cell engager that binds to DLL3 on tumor cells and CD3 on T-cells, triggering a T-cell-mediated immune response against DLL3-expressing tumor cells.
This ongoing Phase I trial, led by Martin Wermke and his team, is evaluating BI 764532 in patients with locally advanced/metastatic DLL3-positive small-cell lung cancer (SCLC), extrapulmonary neuroendocrine carcinoma, or LCNEC.
The primary objective of Phase Ia is to determine the MTD and/or recommended dose for expansion. Secondary objectives include safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy.
Patients received BI 764532 intravenously in 4 regimens that were Regimen A (fixed dose every 3 weeks), Regimen B1 (fixed dose weekly), and Regimens B2 and B3 (step-in dose followed by target dose). Treatment continued until disease progression, unacceptable toxicity, withdrawal, or a maximum of 36 months.
As of February 21, 2024, 168 patients had received at least one dose of BI 764532. The study reported 6 dose-limiting toxicities (DLTs), but none occurred in patients with LCNEC. The MTD was not reached. About 14 patients with LCNEC were treated. The most common treatment-related adverse events (TRAEs) were CRS (36%), dysgeusia (36%), asthenia (21%), and nausea (21%).
In 13 evaluable patients with LCNEC, ORR/DCR across all dose levels was 54%/77% (70%/90% in patients who received ≥90 µg/kg). The median duration of response (DoR) has not been reached. The estimated 6-month rates of DoR and progression-free survival (PFS) were 63% and 28%, respectively, with a median PFS of 3.6 months.
The study concluded that BI 764532 shows promise in treating LCNEC, demonstrating an ORR of 70% at active dose levels with a manageable safety profile.
The trial was sponsored by Boehringer Ingelheim.
Source: https://cattendee.abstractsonline.com/meeting/20598/presentation/741
Clinical Trial: https://clinicaltrials.gov/study/NCT04429087
Wermke M, Gambardella V, Kuboki Y, et al. (2024). “Phase I trial of DLL3/CD3 IgG-like T-cell engager BI 764532 in patients with DLL3-positive tumors: patients with LCNEC.” Presented at: World Conference on Lung Cancer (WCLC); September 8, 2024; Singapore. September 9, 2024.
