Amgen takes Imdelltra front line

Amgen, fresh from a phase 3 win in second-line small-cell lung cancer, is taking its DLL3-targeting T-cell engager Imdelltra into untreated disease. The company said last week during its first-quarter earnings that it would start the first-line Dellphi-312 study by mid-year.

There aren’t many details yet on trial design, but Amgen plans to combine Imdelltra with chemo and AstraZeneca’s checkpoint inhibitor Imfinzi.

Imdelltra’s 2024 accelerated approval, in second-line extensive-stage SCLC based on the uncontrolled Dellphi-301, was controversial, with questions about protocol deviations and the under-reporting of adverse events. Amgen has a chance to draw a line under this with a recent victory in the confirmatory Dellphi-304 study – which is set to feature as an ASCO late-breaker.

Imdelltra sold $115m in 2024, and another $81m in the first quarter of 2025, but expansion into first-line disease would give the drug a real boost.

The company already has an ongoing front-line phase 3, Dellphi-305; however, this is testing maintenance therapy. In the maintenance setting, the phase 1 Dellphi-303 study found a median progression-free survival of 5.6 months with Imdelltra plus either Imfinzi or Tecentriq. Presenting the data at last year’s World Lung meeting, Dr Sally Lau of the Perlmutter Cancer Center flagged a historical 2.6-month PFS for Tecentriq in first-line maintenance.

Other interesting but early avenues of research for Imdelltra include a subcutaneous version, and a combination with MediLink’s B7-H3-targeting ADC YL201, under a clinical trial collaboration signed last October.

Amgen isn’t the only one to go down this mechanistic path: Merck & Co, for example, is testing its anti-DLL3 TCE gocatamig (MK-6070), gained through its $680m purchase of Harpoon, alongside its Daiichi-partnered B7-H3-targeting ADC ifinatamab deruxtecan. A phase 1/2 of the combo in relapsed/refractory SCLC started in February, while an earlier phase 1/2 study of gocatamig in SCLC and neuroendocrine tumours was amended to include ifinatamab-dxd. Data from this combo cohort could come in 2026 or 2027, Merck has said.

Various anti-B7-H3 ADCs have shown promise in SCLC, but MediLink’s YL201 is the only one that’s currently unpartnered.

Notable trials of Imdelltra

Note: AA=accelerated approval; ES=extensive stage; LS=limited stage. Source: OncologyPipeline, clinicaltrials.gov & company releases.