Boehringer takes Imdelltra's 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 suggests Boehringer wants to advance quickly into earlier settings rather than compete 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 is testing 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 may be where obrixtamig stands out. ESMO discussant Helena Linardou noted the 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 earlier lines, 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 trials

Source: OncologyPipeline.