Abstract LB-A005: DAREON-8: A Phase I trial of first-line obrixtamig plus chemotherapy and atezolizumab in extensive-stage small cell lung carcinoma (ES-SCLC)

Abstract Background Obrixtamig (BI 764532) is a DLL3/CD3 IgG-like T-cell engager. We report the first safety and efficacy data for the dose-escalation part of the Phase I DAREON-8 (NCT06077500) trial investigating obrixtamig + first-line (1L) standard of care (SOC; carboplatin + etoposide + atezolizumab) in patients (pts) with ES-SCLC. Methods Pts received intravenous obrixtamig as step-up dosing followed by the target dose (3 dose levels) plus SOC. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Obrixtamig treatment (Tx) was continued until progression, unacceptable toxicity, or pt withdrawal. The primary endpoint was occurrence of dose-limiting toxicities (DLTs) during the maximum tolerated dose (MTD) evaluation period. Secondary endpoints included objective response (investigator assessed) according to RECIST v1.1. Results Pts (n = 22) received ≥1 dose of obrixtamig plus SOC. The median number of cycles of obrixtamig plus SOC was 5 (range: 1–12). Median age was 68 years (range: 44–75); ECOG PS was 0 or 1 in 23%/77% of pts. One obrixtamig-related DLT occurred during the MTD evaluation period (grade 3 tumor-related pain); the MTD was not reached. There were no grade 5 AEs. Treatment-related adverse events (TRAEs) were reported in all patients. The rate of cytopenias was as expected for a chemotherapy-based combination; with only one case of grade 2 neutropenia related to obrixtamig but not SOC. Cytokine release syndrome was observed in 46% of patients, with no grade ≥3 events. No pts discontinued Tx due to TRAEs. The dose-expansion part has been initiated based on the safety observation in dose escalation. Conclusions Obrixtamig + SOC was tolerable with no unexpected toxicities; the MTD was not reached. The frequency and severity of AEs reported with the combination were consistent with the known safety profiles of the individual treatments. The combinability of obrixtamig with chemotherapy and an anti–PD-L1 antibody observed in this trial warrants further development of this combination in 1L ES-SCLC. Citation Format: Solange Peters, Rafal Dziadziuszko, Ewa Kalinka, Anas Gazzah, Sophie Cousin, Maria E. Olmedo, David V. Baz, Tirrell Johnson, Tatsuya Yoshida, Ticiana Leal, Yiyuan Ma, Nicolas Dorleacq, Dian Yang. DAREON-8: A Phase I trial of first-line obrixtamig plus chemotherapy and atezolizumab in extensive-stage small cell lung carcinoma (ES-SCLC) abstract. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr LB-A005.