The phase 3 DeLLphi-305 trial tested whether adding tarlatamab before the cancer returned could keep it controlled longer. The results, presented at the 2026 European Society for Medical Oncology (ESMO) conference and published in The New England Journal of Medicine, showed a meaningful improvement in survival.

Tarlatamab as a Maintenance Therapy

The trial included 563 people with extensive-stage small cell lung cancer. Extensive-stage means the cancer has spread beyond one area of the lung and cannot be treated with radiation to a single field.

Patients first received four cycles of platinum chemotherapy, etoposide, and the immunotherapy drug durvalumab. When cancer shrank or remained stable, those patients then received either:

• Tarlatamab plus durvalumab
• Durvalumab alone

This next phase is called maintenance therapy. It is treatment given after the first, more intensive treatment to keep the cancer controlled for as long as possible.

Tarlatamab (brand name: Imdelltra) is a bispecific T-cell engager. One part attaches to DLL3, a protein found on many small cell lung cancer cells. The other attaches to immune cells called T cells. This brings the immune system close enough to find and attack the cancer.

What Did the Trial Show?

Median overall survival was 21.1 months with tarlatamab and durvalumab, compared with 12.7 months with durvalumab alone. The combination reduced the risk of death by 58%.

At one year, 79% of patients receiving the combination were alive, compared with 53% receiving durvalumab alone.

The median is the midpoint, meaning half of the patients lived longer, and half lived for a shorter time. These numbers do not predict exactly how long one person will live.

There is also an important detail: survival was measured from the beginning of maintenance therapy, after patients had completed their first chemotherapy and immunotherapy. It was not measured from diagnosis.

Median progression-free survival, the time before the cancer grew or spread, was 7.4 months with the combination and 1.9 months with durvalumab alone. At one year, 38% of patients receiving the combination had not experienced progression, compared with 10% in the control group.

“What this shows is that by giving tarlatamab with durvalumab in the maintenance setting, patients have longer-term disease control and they live longer,” Dr. Sands explains.

What This Could Mean for Patients

Tarlatamab is currently approved after small cell lung cancer progresses during or after platinum chemotherapy. DeLLphi-305 suggests it may be more effective to use the drug earlier, while the cancer is still controlled.

If the FDA expands its approval, doctors may discuss tarlatamab immediately after initial chemotherapy and durvalumab. Dr. Sands believes the results support the combination as a new maintenance standard.

This does not mean every patient will have years of disease control. But some patients remained free from progression well beyond the median, which offers real reason for hope.

“On the best end, patients can live for years,” Dr. Sands says.

Side Effects and Early Monitoring

Tarlatamab can cause cytokine release syndrome, or CRS. This happens when activated immune cells release inflammatory signals into the blood. Symptoms may include fever, chills, dizziness, low blood pressure, or trouble breathing.

CRS occurred in about half of patients receiving tarlatamab, but nearly all cases were mild or moderate. Only one patient, or 0.4%, had grade 3 CRS. There were no grade 4 or fatal cases.

WATCH: What is Cytokine Release Syndrome (CRS) and How is It Managed?

A neurologic reaction called ICANS occurred in 1.1% of patients. ICANS can cause confusion, unusual sleepiness, or trouble speaking. No grade 3 or higher cases occurred.

In the study, U.S. patients were observed in the infusion clinic for one to two hours after the first two tarlatamab doses. Final routine monitoring requirements will depend on FDA instructions and the treatment center.

Grade 3 or higher treatment-related side effects occurred in 20.9% of patients receiving the combination and 10.8% receiving durvalumab alone. Only 3.2% stopped tarlatamab because of a treatment-related side effect. Dr. Sands explains that altered taste could be a possible long-term concern.

The results do not mean that extensive-stage small cell lung cancer is cured. They do show that longer control and longer survival are possible. For a cancer that often returns quickly, that is a meaningful change.

Questions to Ask Your Doctor

• Am I a candidate for tarlatamab maintenance therapy?
• What monitoring would I need after the first doses?
• What symptoms should my caregiver and I watch for?
• Are there any clinical trials I should consider joining?

Learn more about SurvivorNet's rigorous medical review process.

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