Dr Strosberg on Research Clarifying the Role of Obrixtamig in SCLC and Other Neuroendocrine Cancers

"Currently, there’s no standard…treatment beyond platinum etoposide for poorly differentiated neuroendocrine carcinomas. [Accordingly, the DAREON-5] study is looking at obrixtamig [for] patients [with SCLC and NECs] who have at least received 1 prior line of treatment."

Jonathan Strosberg, MD, a professor and leader of the Neuroendocrine Tumor Division and the Department of Gastrointestinal Oncology Research Program at Moffitt Cancer Center, discussed how the ongoing phase 2 DAREON-5 trial (NCT05882058) may clarify the role of obrixtamig (BI 764532)—a bispecific T-cell engager targeting delta-like ligand-3 (DLL3) and CD3—in the treatment of patients with extensive-stage small cell lung cancer (SCLC), extrapulmonary neuroendocrine carcinomas (NECs), and large-cell NEC of the lung.

Strosberg noted that patients with poorly differentiated NECs currently have limited treatment options beyond platinum-based chemotherapy. In gastrointestinal NECs, regimens such as FOLFIRINOX (leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin) may be employed, and dual checkpoint inhibition with ipilimumab (Yervoy) and nivolumab (Opdivo) has demonstrated modest activity, with response rates of approximately 10% to 15% in real-world datasets, he added. However, there remains no widely accepted or effective second-line standard of care (SOC), Strosberg emphasized.

DAREON-5 is an open-label, multicenter trial evaluating obrixtamig in adult patients with extensive-stage SCLC and other NECs, Strosberg continued. Eligible patients with SCLC must have received at least 2 prior lines of therapy, including platinum-based chemotherapy and a PD-L1 inhibitor, if SOC in their region. Patients with extrapulmonary or large-cell NEC of the lung must have received at least 1 prior platinum-based regimen. Part 1 of the study includes safety run-in and dose expansion phases, and part 2 focuses on efficacy.

The primary end point for parts 1 and 2 is objective response rate (ORR) as assessed by RECIST 1.1 criteria, and rate of treatment-emergent adverse effects (TEAEs) is an additional primary end point for part 1. Secondary end points include duration of response, progression-free survival, disease control rate, overall survival, health-related quality of life, and TEAEs leading to treatment discontinuation.

Strosberg emphasized that ORR is an appropriate primary end point in this single-arm study, given the absence of effective therapies in this setting and the observation that responses to obrixtamig appear to be durable. The trial may offer insights into the utility of DLL3-targeted therapies across NEC subtypes and help address an urgent unmet need, he concluded.