BI 764532

Overview

Obrixtamig (BI 764532) is an investigational, intravenously administered, IgG-like bispecific T-cell engager being developed for cancers expressing delta-like ligand 3 (DLL3), particularly small-cell lung cancer (SCLC), extrapulmonary neuroendocrine carcinoma (epNEC), and large-cell neuroendocrine carcinoma of the lung (LCNEC-L). Clinical development has advanced to randomized phase III trials, but efficacy evidence currently consists primarily of nonrandomized early-phase studies. (pmc.ncbi.nlm.nih.gov)

Mechanism of action

One arm of obrixtamig binds DLL3 on tumor cells and the other binds CD3 on T cells, bringing the cells together and inducing T-cell activation and tumor-cell lysis. Preclinical studies demonstrated DLL3-dependent cytotoxicity, T-cell infiltration, and tumor regression in SCLC models. (drugs.ncats.io)

Efficacy

In the peer-reviewed phase I monotherapy trial, 168 previously treated patients with DLL3-positive SCLC, epNEC, or LCNEC-L received escalating doses:

• Across all doses and tumor types, the objective response rate (ORR) was 23%; median duration of response was 8.5 months, with an estimated 70% of responses lasting at least six months.
• In the step-up dosing groups receiving effective doses, ORR was 28% overall: 21% in SCLC, 27% in epNEC, and 70% in LCNEC-L. The LCNEC-L estimate was based on a small subgroup. (ascopubs.org)
• A subsequent epNEC analysis suggested greater activity in tumors with high DLL3 expression: ORR was 40% and median response duration 7.9 months in DLL3-high disease. In a 20-patient genitourinary epNEC subgroup, ORR was 50% in DLL3-high tumors versus 0% in DLL3-low tumors. (ascopubs.org)

Preliminary phase Ib data for obrixtamig plus topotecan in relapsed SCLC showed a 69% confirmed ORR among 23 evaluable patients, including one complete response, and an 87% disease-control rate. These small, nonrandomized combination results require confirmation. (ascopubs.org)

Safety

In the 168-patient monotherapy trial, the most frequent treatment-related toxicity was cytokine-release syndrome (CRS), occurring in 57% of patients and at grade 3 or higher in 3%. CRS generally arose during early treatment, had a median duration of two days, and was usually reversible. Other common treatment-related events included taste disturbance, fever, fatigue/asthenia, and decreased lymphocyte counts. Grade 3 or higher treatment-related adverse events occurred in approximately 24%; treatment-related dose reductions and discontinuations occurred in approximately 2% and 4%, respectively. Rare severe or fatal neurologic events, including immune effector cell-associated neurotoxicity syndrome (ICANS), were reported. The maximum tolerated dose was not reached. (ascopubs.org)

With obrixtamig plus topotecan, CRS was grade 1 in 44% and grade 2 in 4%, with no grade 3 or higher CRS. Grade 3–4 cytopenias were frequent, consistent with topotecan toxicity. (ascopubs.org)

Further reading

• Peer-reviewed phase I monotherapy results — Journal of Clinical Oncology
• Preclinical DLL3/CD3 T-cell-engager study — Clinical Cancer Research
• Phase Ib obrixtamig plus topotecan results — Journal of Clinical Oncology
• Genitourinary epNEC subgroup analysis — Journal of Clinical Oncology
• EMA orphan-designation summary

Last updated: Sep 2026