Dr Wermke on the Efficacy and Safety of Obrixtamig With Topotecan in Advanced SCLC

“We really have something that goes beyond the effect of either component alone, at least this is what we think from the limited data set we have thus far, but it's certainly something we need to follow up on.”

Martin Wermke, MD, group leader, Thoracic Oncology Group, professor for experimental cancer therapy, head of the Early Clinical Trial Unit and of the Trial Management National Center for Tumor Diseases Dresden (NCT/UCC) Clinical Trial Center, highlighted the clinical potential of obrixtamig, a DLL3/CD3-directed bispecific T-cell engager, in combination with topotecan for the treatment of patients with advanced small cell lung cancer (SCLC), based on early-phase data from the ongoing phase 1 DAREON-9 trial (NCT05990738).

The trial utilized a step-up dosing strategy for obrixtamig to mitigate immune-mediated toxicities. The study enrolled patients who progressed after 1 or more lines of platinum-based treatment with or without a PD-1/PD-L1 inhibitor. Three dose levels of obrixtamig were evaluated in the study.

Interim results showed an encouraging overall response rate (ORR) of 70% (95% CI, 47%-87%), with responses maintained at 69% (95% CI, 39%-91%) among the 13 patients who underwent confirmatory imaging. Wermke noted that these early findings may suggest synergistic activity between obrixtamig and topotecan, warranting further exploration.

Wermke noted that safety outcomes were consistent with expectations based on the known toxicity profiles of each agent alone. Topotecan-associated cytopenias were reported, including neutropenia (68%) and thrombocytopenia (92%), though no associated infectious or bleeding complications occurred.

Obrixtamig-related cytokine release syndrome (CRS) occurred in 48% of patients; these were mostly grade 1 effects (44%), with a few grade 2 cases (4%). No grade 3 or higher CRS was observed. Additionally, neurotoxicity including immune effector cell–associated neurotoxicity syndrome was rare, with only two patients experiencing grade 1 or 2 muscle spasms.