Phase 3 results — presented at ESMO 2026, published in NEJM (2026-10-24) Later-line use: approved in the US, Japan and UK First-line maintenance: not yet approved (phase 3 completed)
The small cell lung cancer drug tarlatamab (brand name Imdelltra) cut the risk of death by 58% in a phase 3 trial of maintenance therapy given right after first treatment for extensive-stage disease. Patients who received tarlatamab with the immunotherapy durvalumab (Imfinzi) had a median overall survival of 21.1 months, more than 8 months longer than with durvalumab alone (12.7 months). The results were presented at the ESMO Presidential Symposium on October 24, 2026 and published the same day in the NEJM.
Tarlatamab brings T cells right next to cancer cells
Small cell lung cancer grows quickly and spreads early. Many people are already at the "extensive" stage, with spread beyond the lung, when they are diagnosed. Until now, standard first-line treatment for extensive-stage disease has been platinum chemotherapy and etoposide plus an immunotherapy drug, followed by maintenance with the immunotherapy alone. With this approach, median survival has generally been about 12–13 months.
Tarlatamab is a bispecific T-cell engager (BiTE). One arm binds CD3 on T cells; the other binds DLL3, a protein found in large amounts on small cell lung cancer cells. By holding the two cells together, it lets the T cell attack the cancer cell directly. Unlike CAR-T, which is made from a patient's own cells, it is a ready-to-use injectable drug. For an overview of immune cell treatments, see types of immune cell therapy compared.
Tarlatamab had already shown benefit as a later-line treatment. The DeLLphi-305 trial moved it earlier, into maintenance right after first treatment. Dr. Jacob Sands of Dana-Farber Cancer Institute, who presented the data, said the combination "sets a new standard of care."
Who is it for? People with extensive-stage disease that has not progressed after first-line chemotherapy
The trial enrolled 563 people at 175 sites in 29 countries, randomized 1:1. Key entry criteria were:
- Adults with extensive-stage small cell lung cancer
- Four cycles of platinum and etoposide, with durvalumab given in at least three of them
- No disease progression after first-line treatment
- Good performance status (ECOG 0–1)
People with brain metastases without symptoms could take part whether or not these had been treated; about 20% of participants had brain metastases, and about one third had liver metastases. Treatment options for brain metastases are covered in our article on stereotactic radiation for brain metastases.
Results: 21.1 months median survival and 79% alive at one year
This was a pre-planned interim analysis using data collected up to July 7, 2026, with a median follow-up of about 16 months. Survival was measured from the start of maintenance therapy.
| Measure | Tarlatamab + durvalumab | Durvalumab alone |
|---|---|---|
| Median overall survival | 21.1 months | 12.7 months |
| Hazard ratio for death | 0.42 (58% lower risk of death) | |
| 1-year survival | 79.4% | 53.3% |
| Median progression-free survival | 7.4 months | 1.9 months |
| 1-year progression-free survival | 38.4% | 9.5% |
| Objective response rate | 26.4% | 4.1% |
| Median duration of response | 12.7 months | 5.6 months |
Sources: ESMO 2026 LBA3, NEJM 2026 (Pérol et al.). A hazard ratio below 1 favors the treatment; progression-free survival is the time without cancer growth.
The survival benefit was similar across subgroups, including people with brain or liver metastases. Dr. Stephen Liu of Georgetown Lombardi Comprehensive Cancer Center called the longer time without relapse "quite remarkable." It is the first phase 3 trial in which a bispecific T-cell engager improved overall survival as first-line maintenance in small cell lung cancer.
Side effects and management: watching for cytokine release syndrome after the first two doses
The most common side effect was cytokine release syndrome (CRS), a reaction in which immune cells activate all at once, causing fever, chills or low blood pressure. It occurred in 49.6% of the tarlatamab group, mostly grade 1 (41.8%) or grade 2 (7.4%). One patient (0.4%) had grade 3, and there were no grade 4 or fatal cases. It usually appeared about a day after one of the first two doses.
Immune effector cell-associated neurotoxicity syndrome (ICANS) was rare at 1.1%, all grade 2 or lower. 5.7% of patients stopped tarlatamab because of side effects. Treatment-related grade 3 or higher side effects occurred in 20.9%, compared with 10.8% with durvalumab alone. Low white blood cell counts, loss of appetite, fatigue, weight loss and taste changes were also reported.
Monitoring is therefore built into the schedule. Tarlatamab is given as a one-hour intravenous infusion: 1 mg on day 1, 10 mg on days 8 and 15, then 10 mg every 2 weeks. The US prescribing information recommends 22–24 hours of monitoring in a healthcare setting after the day 1 and day 8 doses, then staying within one hour of a hospital with a caregiver for 48 hours. For a similar approach to CRS care, see the CAR-T treatment process.
Where is it available? Later-line use is approved in Japan and the US
- United States: accelerated approval in May 2024, then full approval on November 19, 2025 for extensive-stage small cell lung cancer that progressed after platinum chemotherapy. In the supporting DeLLphi-304 phase 3 trial, median survival was 13.6 months versus 8.3 months with standard chemotherapy.
- Japan: approved in December 2024 and listed on the national health insurance price list on April 16, 2025. In March 2026 the label was revised, based on phase 3 data, to widen second-line use. A phase 1b trial of subcutaneous tarlatamab (DeLLphi-308, jRCT2061240070) is also recruiting in Japan.
- United Kingdom: approved by the MHRA on December 31, 2024, for use after two previous treatments.
- First-line maintenance: as of November 2026, not yet approved in any country. These phase 3 results are expected to support future regulatory reviews.
For another lung cancer advance, see savolitinib after Tagrisso resistance.
What to check and questions for your doctor
- Is my disease extensive-stage? Is it considered stable after first-line chemotherapy?
- Can tarlatamab be added to durvalumab maintenance in my country now?
- What are the conditions for receiving tarlatamab as second-line treatment?
- How long will I need to stay in hospital or be monitored for the first two doses?
- Whom should I contact if I develop fever, dizziness or slurred speech?
Frequently asked questions
What is the small cell lung cancer drug tarlatamab?
It is a bispecific antibody injection that binds both T cells and the DLL3 protein on small cell lung cancer cells, so the T cells attack the cancer. Its brand name is Imdelltra, and it was developed by Amgen in the US.
How good were the DeLLphi-305 results?
In 563 people with extensive-stage disease that had not progressed after first-line chemotherapy, adding tarlatamab to durvalumab gave a median survival of 21.1 months versus 12.7 months with durvalumab alone. The risk of death was 58% lower, and 79.4% were alive at one year.
How are tarlatamab side effects managed?
The most common, cytokine release syndrome, was mostly grade 1–2 and usually occurred after the first two doses. Patients are monitored in a healthcare setting at that time, and most cases settled with supportive care such as fever reducers and fluids.
Is tarlatamab available in Japan?
Yes. It was approved in Japan in December 2024 and has been covered by national health insurance since April 2025. Current approval covers small cell lung cancer that has progressed after chemotherapy; first-line maintenance is not yet approved.
Related: Keytruda for TMB-high solid tumors: FDA full approval · Phase 3 treatment after Tagrisso resistance · All articles by cancer type
Sources
- NEJM — Pérol M, et al. Tarlatamab–Durvalumab Maintenance for Extensive-Stage Small-Cell Lung Cancer (2026)
nejm.org
Checked: 2026-11-02 - News-Medical / Dana-Farber — Immunotherapy combination sets a new standard of care for extensive-stage small cell lung cancer (2026-10-26)
news-medical.net
Checked: 2026-11-02 - Targeted Oncology — ESMO 2026 Presidential Symposium I late-breaking recap (DeLLphi-305, LBA3)
targetedonc.com
Checked: 2026-11-02 - OncoDaily — DeLLphi-305: Tarlatamab–Durvalumab Redefines First-Line Maintenance in Extensive-Stage SCLC (ESMO 2026)
oncodaily.com
Checked: 2026-11-02 - pharmaphorum — ESMO26: “Unprecedented” results from DeLLphi-305 in SCLC
pharmaphorum.com
Checked: 2026-11-02 - Amgen — IMDELLTRA in combination with IMFINZI demonstrated landmark improvement in overall survival (2026-09)
amgen.com
Checked: 2026-11-02 - Oncology Practice Management — FDA grants traditional approval to tarlatamab-dlle (2025-11-19, DeLLphi-304)
oncpracticemanagement.com
Checked: 2026-11-02 - PharmaJapan — Amgen rolls out Imdelltra for SCLC in Japan (2025-04)
pj.jiho.jp
Checked: 2026-11-02 - PharmaJapan — Amgen wins label update for Imdelltra in Japan following phase 3 data (2026-03)
pj.jiho.jp
Checked: 2026-11-02 - GOV.UK (MHRA) — Tarlatamab approved to treat adult patients with small cell lung cancer (2024-12-31)
gov.uk
Checked: 2026-11-02 - ClinicalTrials.gov — NCT06211036: DeLLphi-305
clinicaltrials.gov/study/NCT06211036
Checked: 2026-11-02 - jRCT — jRCT2061240070: DeLLphi-308 (subcutaneous tarlatamab, Japan)
jrct.mhlw.go.jp
Checked: 2026-11-02
Written by the FTH editorial team. Sources checked 2026-11-02 · Medical review: not applicable
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your medical team.
