Dr Peters on Obrixtamig Plus Atezolizumab/Chemo in First-Line ES-SCLC

Higher doses [of obrixtamig] were [evaluated later in the study], so we need to wait to see [how] these patients [do] over time [in terms of] toxicity. However, if this continues to be feasible and safe, the main question is, is it better to give this T-cell engager immediately [at] cycle 1, day 1? Or should we wait for maintenance or wait for the second line?

Solange Peters, MD, PhD, chair of the Medical Oncology Department at Lausanne University Hospital in Switzerland, discussed findings from the phase 1 DAREON-8 trial (NCT06077500), which evaluated obrixtamig (BI 764532) in combination with carboplatin, etoposide, and atezolizumab (Tecentriq) as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC).

During the 2025 ESMO Congress, investigators presented results from the dose-escalation portion of the study, which assessed dose-limiting toxicities, the maximum tolerated dose (MTD), and overall tolerability of the regimen.

Efficacy findings demonstrated that evaluable patients treated in the first-line setting (n = 28) achieved a confirmed overall response rate (ORR) of 68% (95% CI, 49%-82%) and a confirmed disease control rate of 89% (95% CI, 73%-96%). Best overall responses comprised complete response (4%), partial response (64%), stable disease (21%), progressive disease (4%), and not evaluable/missing (7%).

The median duration of response was 7.3 months (95% CI, 4.4-not calculable). Additionally, the median progression-free survival (PFS) was not reached, and patients experienced 3-, 6-, and 9-month PFS rates of 96% (95% CI, 89%-100%), 73% (95% CI, 55%-92%), and 52% (95% CI, 27%-77%), respectively.

According to Peters, the combination demonstrated a manageable safety profile with no unexpected toxicities, and the MTD was not reached. Obrixtamig-related adverse effects (AEs) of any grade occurred in 96% of patients, including 39% who had grade 3 or higher AEs related to the agent. The most common AEs related to obrixtamig in at least 25% of patients included cytokine release syndrome (any-grade, 50%; grade ≥3, 0%), dysgeusia (39%; 0%), decreased appetite (32%; 0%), neutropenia (29%; 21%), pyrexia (29%; 0%), anemia (25%; 0%), and fatigue (25%; 4%). No instances of grade 3 or higher immune effector cell–associated neurotoxicity syndrome (ICANS) were reported; grade 1 and grade 2 ICANS were reported in 1 patient each (4%).

In terms of the overall safety profile of the combination, the most common grade 3 or higher treatment-emergent AEs (TEAEs) were cytopenias and were related to chemotherapy. Grade 3 or higher TEAEs occurred in 79% of patients, including 75% who had grade 3 or higher TEAEs related to chemotherapy. The most common grade 3 or higher TEAEs included neutropenia (all instances, 54%; related to chemotherapy, 54%), anemia (18%; 18%), decreased neutrophil count (14%; 14%), asthenia (11%; 4%), and thrombocytopenia (7%; 7%).

Peters explained that future analyses will help determine the optimal timing of obrixtamig administration—whether it should be given at cycle 1, day 1 alongside chemotherapy and immunotherapy, or whether it should be held for maintenance or as a second-line treatment. These forthcoming data will guide the design of subsequent phase 3 randomized trials.

Reference

Peters S, Dziadziuszko R, Kalinka E. DAREON-8: A phase I trial of first-line obrixtamig plus chemotherapy and atezolizumab in extensive-stage small cell lung carcinoma (ES-SCLC). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 2759MO.