In brief
- A planned interim analysis of the Phase III DeLLphi-305 trial reported a statistically significant improvement in overall survival for durvalumab plus tarlatamab against durvalumab alone, given as first-line maintenance in extensive-stage small cell lung cancer.
- Progression-free survival and objective response rate, both secondary endpoints, also reached statistical significance.
- 563 patients whose disease had not progressed after durvalumab-based induction with platinum chemotherapy and etoposide were randomised 1:1.
- No efficacy figures were released. The announcement carries no hazard ratio for either survival endpoint, no median survival in either arm, no response rate and no duration of follow-up.
- Safety was reported as consistent with the known profiles of the two drugs, with no new signals identified and no adverse event rates given.
Study at a glance
- Source trial: DeLLphi-305, global Phase III, randomised, open-label, sponsored by Amgen with partial funding and durvalumab provided by AstraZeneca
- Population: 563 patients with extensive-stage small cell lung cancer whose disease had not progressed after induction; treated and untreated asymptomatic brain metastases were permitted at baseline
- Induction received: durvalumab with carboplatin or cisplatin at investigator’s choice, plus etoposide
- Randomised treatment: durvalumab plus tarlatamab against durvalumab alone, 1:1, until progression or unacceptable toxicity
- Primary endpoint: overall survival, reported as statistically significant at a planned interim analysis
- Secondary endpoints: progression-free survival and objective response rate, both reported as statistically significant
- What was not reported: hazard ratios, median overall and progression-free survival, objective response rates, follow-up duration, adverse event rates
- Safety: consistent with the known profiles of both drugs, no new safety signals identified
563 patients randomised only after induction was complete
DeLLphi-305 tested maintenance rather than induction. Patients entered the randomisation only if their disease had not progressed on standard first-line treatment, which in this trial was durvalumab together with platinum chemotherapy, at the investigator’s choice of carboplatin or cisplatin, and etoposide. The 563 patients who completed that induction were assigned 1:1 to continue durvalumab with tarlatamab added, or to continue durvalumab alone, until progression or unacceptable toxicity. Patients with asymptomatic brain metastases were eligible whether or not those metastases had been treated.
The trial is sponsored by Amgen, with partial funding and durvalumab provided by AstraZeneca. Overall survival is the primary endpoint and progression-free survival a key secondary endpoint. The result announced comes from a planned interim analysis rather than a final one.
Statistically significant on survival, with no hazard ratio or median disclosed
The announcement states that the combination improved overall survival against durvalumab alone, and that progression-free survival and objective response rate also reached statistical significance. It carries no measure of how large any of those differences were: no hazard ratio for either survival endpoint, no median survival in either arm, no response rate for either arm, and no follow-up time at the data cut. The size of the benefit cannot be judged from what has been made public.
AstraZeneca states that the data will be presented at a forthcoming medical meeting and shared with regulatory authorities. The underlying data have not been published or presented, and the description of the improvement as clinically meaningful is the company’s own. AstraZeneca also describes the regimen as the first combination of an immunotherapy with a bispecific T-cell engager to show a survival benefit in this setting.
Measured against a median overall survival of about one year
Checkpoint inhibitors established the current first-line standard in extensive-stage disease and improved overall survival, but median overall survival with that standard is approximately one year. About two-thirds of small cell lung cancer is diagnosed at the extensive stage, and 3.6% of those patients are alive five years after diagnosis, against 18.1% in limited-stage disease. An estimated 195,000 people worldwide will be treated for extensive-stage disease during 2026.
Tarlatamab binds DLL3 on the surface of the tumour cell and CD3 on the T cell, and thereby activates T cells against DLL3-expressing cells. DLL3 is present on small cell tumour cells in about 85% to 96% of patients and is minimally expressed on healthy cells.
“Given the aggressive nature of small cell lung cancer, many patients quickly relapse on current therapy and never reach second-line treatment.”Jacob Sands, MD, Associate Chief of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute
No new safety signals, and observation in clinic after the first two doses
The safety and tolerability profile of durvalumab with tarlatamab was consistent with what is already known about each drug, and no new safety signals were identified, according to the announcement. No adverse event rates were released for either arm, so the tolerability of the combination relative to durvalumab alone cannot yet be quantified.
Patients were observed in a healthcare setting for one to two hours after the tarlatamab infusions on day 1 and day 8 of the first cycle, and for six to eight hours in certain regions including Europe. That observation period applies to each of the first two doses of a regimen that then continues until progression.
Sources
- AstraZeneca. Imfinzi plus Imdelltra demonstrated a statistically significant and highly clinically meaningful improvement in overall survival and progression-free survival in 1st-line extensive-stage small cell lung cancer (2026-09-08). astrazeneca.com
This article was produced independently by the Lung Summit editorial team, without industry funding or input.
