Amgen's Imdelltra with AstraZeneca's Imfinzi cuts small cell lung cancer death risk 58%

Amgen and AstraZeneca reported on Oct 24 that adding Amgen's Imdelltra (tarlatamab) to AstraZeneca's Imfinzi (durvalumab) cut the risk of death by 58% compared with Imfinzi alone in a Phase 3 trial in extensive-stage small cell lung cancer. The interim results from the DeLLphi-305 trial were presented at the European Society for Medical Oncology (ESMO) Congress in Madrid and published the same day in The New England Journal of Medicine.

The trial tested the pair as first-line maintenance treatment, for patients whose cancer had not progressed after initial treatment with Imfinzi, platinum chemotherapy and etoposide. Amgen said in September that the trial had met its overall survival goal but gave no figures at the time.

The results

The trial enrolled 563 patients: 282 received the combination and 281 received Imfinzi alone. The 58% reduction in the risk of death (a hazard ratio of 0.42) came from a planned interim analysis at a median follow-up of about 16 months. The risk of disease progression or death fell by 66%.

AstraZeneca said the survival benefits were consistent across all prespecified patient subgroups, including patients whose cancer had spread to the brain or liver. Amgen also released longer follow-up from DeLLphi-303, an earlier Phase 1b trial of Imdelltra with Imfinzi or Roche's Tecentriq in the same setting, in which median overall survival reached 37.9 months after a median follow-up of 30.8 months.

Safety

Serious treatment-related side effects (grade 3 or higher) occurred in 20.9% of patients on the combination and 10.8% of patients on Imfinzi alone. Cytokine release syndrome, an immune overreaction linked to this class of drug, occurred in 49.6% of patients who received Imdelltra. Nearly all cases were grade 1 or 2, with one grade 3 case.

Who is exposed

Amgen sells Imdelltra, a bispecific T-cell engager that steers the immune system's T cells to attack cancer cells. It was first approved in May 2024, and its current label covers patients whose cancer has progressed after platinum-based chemotherapy. Truist Securities estimated that a first-line maintenance label would raise the drug's addressable US population to about 21,600 patients from about 12,900 under the current label, and Guggenheim Partners forecasts about $1 billion in US Imdelltra sales in 2026.

AstraZeneca sells Imfinzi, the immunotherapy used in both arms of the trial and in the initial treatment all patients received.

Jazz Pharmaceuticals sells Zepzelca, which is already approved with Roche's Tecentriq in the same first-line maintenance setting. In its Phase 3 IMforte trial, that combination cut the risk of death by 27%, with median overall survival of 13.2 months versus 10.6 months for Tecentriq alone.

What comes next

• Amgen said it is moving with urgency to share the DeLLphi-305 results with regulators worldwide and has not given a filing date.
• Amgen reports third-quarter results after the market closes on Nov 3.