People With a Fast-Moving Lung Cancer Lived Longer With an Added Immune Therapy

CATEGORY: IMMUNE HEALTH

For people with extensive-stage small cell lung cancer, the hardest stretch often comes after the first treatment works. Chemotherapy plus immunotherapy beats the disease back, maintenance immunotherapy continues, and then everyone waits, because this cancer usually returns within months. A phase 3 trial called DeLLphi-305 changed what that waiting can look like: adding tarlatamab to standard maintenance stretched median survival to 21.1 months versus 12.7 months, a 58% lower risk of death.¹ At one year, 79% of people on the combination were alive versus 53% on standard maintenance alone.

A Second Guard Posted After the First Assault

The trial enrolled 563 adults at 175 hospitals in 29 countries, all with extensive-stage disease that hadn’t progressed after platinum chemotherapy, etoposide and the immunotherapy durvalumab. From there, a random draw split them evenly: durvalumab maintenance alone, or durvalumab plus tarlatamab. Tarlatamab works like a molecule with two hands. One hand grips a protein found on small cell lung cancer cells, the other grips a T cell, and the forced introduction tells the immune system exactly what to kill. Nobody chose their own arm, though the treatments themselves were open label. Researchers then tracked survival, the trial’s primary endpoint. People whose cancer had already spread to the brain could join if the lesions weren’t causing symptoms, which matters because this disease reaches the brain often, and trials that exclude those patients flatter their own results.¹

Eight Extra Months, and What They Cost

The survival gap was wide for an aggressive cancer: a hazard ratio of 0.42, meaning a 58% lower risk of death during follow-up, with the combination’s median at 21.1 months. Tumors stayed controlled far longer too, a median 7.4 months versus 1.9 before progression, and at the one-year mark 38% of the combination group remained progression-free against 10% of the comparison group. Among people with measurable tumors, 26.4% saw their cancer shrink on the combination versus 4.1% on durvalumab alone, and those responses lasted a median 12.7 months rather than 5.6. The price was a distinctive side effect. Half the people getting tarlatamab, 49.6%, developed cytokine release syndrome, a flood of immune signaling that brings fever and low blood pressure. Nearly all of it was mild; 7.4% was moderate, one case was severe, and none was fatal. It also arrived predictably, typically within a day of an infusion, which is why early doses come with hours of observation. About one in five patients needed steroids to settle it. Severe or worse side effects overall ran 46.8% versus 40.6%, and only 5.7% stopped tarlatamab over side effects. No deaths in the combination arm were attributed to treatment.¹

What an Interim Answer Does and Doesn’t Settle

These results come from a planned interim analysis, so the final survival numbers can still shift, and the trial was funded by Amgen, tarlatamab’s maker. The drug is already approved in the US for small cell lung cancer that has progressed after chemotherapy; this earlier, maintenance use isn’t approved yet. The control arm’s 12.7-month median is itself a fair picture of what current first-line care achieves in this disease. Against that baseline, an 8.4-month gain in the median is a large move in a disease where progress has come slowly. Small cell lung cancer grows fast, spreads early and is tightly bound to smoking. That’s the population this trial speaks to. If regulators approve the earlier use, the first months after diagnosis would become the moment this drug goes to work. The results were published in the New England Journal of Medicine the same day they were presented at the European cancer congress.¹

Key Takeaways

• Adding tarlatamab to maintenance durvalumab raised median survival from 12.7 to 21.1 months in extensive-stage small cell lung cancer.
• Cytokine release syndrome hit about half of those on tarlatamab but was almost always mild and never fatal in the trial.
• The findings are interim, the maintenance use isn’t yet approved, and the trial was run and funded by the drug’s maker.

References

1. Pérol M, Yoshida T, Ahn MJ, et al. Tarlatamab–Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer. New England Journal of Medicine. 2026; NEJMoa2609482. link