Group leader of the Thoracic Oncology Group, 

Professor for Experimental Cancer Therapy, Head of Early Clinical Trial Unit, and Head of Trial Management NCT Clinical Trial Center.

WERMKE

“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.

Videos

Martin Wermke, MD, discusses obrixtamig in combination with topotecan for the treatment of patients with  advanced small cell lung cancer. 

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

Martin Wermke, MD, head, the Early Clinical Trial Unit, the National Center for Tumor Diseases Dresden, the University Hospital Carl Gustav Carus Dresden, the Technical University of Dresden, discusses the investigation of BI 764532 in patients with DLL3-positive small cell lung cancer (SCLC) and neuroendocrine carcinoma (NEC).

At the 2023 ASCO Annual Meeting, Wermke and colleagues presented data

 on the use of the novel DLL3-targeting T-cell engager in a phase 1 trial (NCT04429087), where data showed BI 764532 elicited tumor shrinkage across all tumor types., and patients treated with BI 764532 at doses of 90 μg/kg and higher (n = 71) achieved an overall response rate (ORR) of 25% and a disease control rate (DCR) of 52%. Although the maximum tolerated dose was not reached, 5 dose-limiting toxicities (DLTs) were reported, including grade 3/4 cytokine release syndrome (CRS; n = 2), grade 3 confusional state (n = 1), grade 2 infusion-related reaction (n = 1), and grade 3 nervous system disorder (n = 1). However, all DLTs were reversible, and all patients recovered.

A total of 107 patients were treated in the dose-escalation portion of the study, Wermke says. Dosing began at once every 3 weeks, then continued to a weekly regimen, with the goal of reducing the incidence of CRS, he adds.

The observed responses do not appear to be restricted to a specific tumor type, he continues, noting that investigators have seen durability in the responses thus far. At the time of the data cutoff, 14 out of 18 responders were ongoing, and some patients have been in response for at least one year, Wermke concludes.

Martin Wermke, MD, discusses the investigation of BI 764532 in patients with DLL3-positive small cell lung cancer and neuroendocrine carcinoma.


Martin Wermke, MD

Articles

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

Dr Wermke on the Investigation of BI 764532 in DLL3+ SCLC and NEC