Boehringer takes Imdelltra rival straight to first line

Boehringer Ingelheim is taking its DLL3-targeting T-cell engager obrixtamig straight from phase 1 into a pivotal trial in first-line extensive-stage small-cell lung cancer, according to a recent posting on clinicaltrials.gov.This shows Boehringer wanting to advance quickly into early settings rather than competing in the crowded second-line space, where Amgen already holds full approval for its DLL3-targeting bispecific Imdelltra. Still, Amgen has front-line hopes of its own.The new phase 3 trial, Dareon-Lung-1, will evaluate obrixtamig in combination with the standard-of-care regimen Tecentriq plus chemo, versus Tecentriq plus chemo alone, with overall survival as the primary endpoint.This looks like a similar approach to the one Amgen is taking with one of its front-line pivotal trials in ES-SCLC, Dellphi-312, which tests Imdelltra plus Imfinzi and chemo as induction therapy, followed by Imdelltra plus Imfinzi as maintenance.Durability advantage?Boehringer's pivotal design builds on data presented at ESMO from the uncontrolled phase 1 Dareon-8, which tested induction with obrixtamig plus Tecentriq and chemo, followed by maintenance with obrixtamig plus Tecentriq, in first-line ES-SCLC. Among 28 patients the response rate was 68%, comparable to historical chemo-immunotherapy outcomes in this setting.Durability could be where obrixtamig stands out. The ESMO discussant, Dr Helena Linardou, noted a potential benefit in progression-free survival, as 52% of patients remained progression-free at nine months.Safety is also central to the earlier-line push. Moving T-cell engagers into early treatment, when patients are fitter, could help blunt cytokine-release syndrome, a class-defining toxicity. In Dareon-8 50% of patients experienced this adverse event, all of whom had grade 1 or 2 events.Still, the approach also raises a question: is the checkpoint inhibitor necessary? As noted by the ESMO discussant, immunotherapy has historically shown modest activity in first-line SCLC. Even so, both Boehringer and Amgen have opted to retain checkpoint inhibitors in their respective regimens, and neither appears ready to test their T-cell engagers in combination with chemotherapy alone in this setting.Amgen also has phase 3 studies ongoing in first-line ES-SCLC maintenance and in limited-stage SCLC, a potentially curative setting. It will be interesting to see if Boehringer also follows suit here.  Selected DLL3-targeting bispecifics in first-line pivotal trialsTrialSettingRegimenPrimary endpointNotePh3 Dellphi-3051st-line ES-SCLC (maintenance)+Imfinzi, vs ImfinziOSCompletes Jul 2027Ph3 Dellphi-3061st-line LS-SCLC (maintenance)Vs placeboPFSCompletes Mar 2030; Imfinzi was approved in this setting in Dec 2024Ph3 Dellphi-3121st-line ES-SCLC+ Imfinzi + chemo, vs Imfinzi + chemoOSCompletes Jan 2029Ph3 Dareon-Lung-11st-line ES-SCLC+ Tecentriq + chemo, vs Tecentriq + chemoOSStarts Apr 2026Source: OncologyPipeline.