Amgen's Imdelltra Plus Imfinzi Hits Primary Endpoint in First-Line ES-SCLC Maintenance
核心洞察
The Phase III DeLLphi-305 trial met its primary endpoint, showing tarlatamab plus durvalumab significantly improved overall survival versus durvalumab alone in extensive-stage SCLC.
The combination also improved progression-free survival and objective response rate as first-line maintenance in patients whose disease had not progressed after induction therapy.
Amgen and AstraZeneca reported the survival benefit at a planned interim analysis, with full data to be presented at an upcoming medical meeting.
Amgen and AstraZeneca have reported positive high-level Phase III results from the DeLLphi-305 trial, showing that adding Imdelltra (tarlatamab) to Imfinzi (durvalumab) as first-line maintenance therapy significantly improved overall survival (OS) compared with durvalumab alone in patients with extensive-stage small cell lung cancer (搜索) (ES-SCLC).
The study met its primary endpoint at a prespecified interim analysis, according to the companies, demonstrating a statistically significant and clinically meaningful improvement in OS. The combination also produced improvements in progression-free survival (PFS) and objective response rate (ORR). The trial enrolled patients whose disease had not progressed after standard induction therapy with platinum, etoposide and durvalumab.
The safety profile of the dual regimen was consistent with what is already known about the two individual medicines, the companies reported. Full results are expected to be shared with the scientific community at an upcoming medical meeting.
A DLL3-Targeted Bispecific Moves Earlier
Imdelltra is a DLL3xCD3 bispecific T-cell engager (TCE) that was approved in the United States for accelerated use on May 16, 2024, for ES-SCLC patients with disease progression on or after platinum-based chemotherapy. The drug has become a key growth product for Amgen, with sales reaching $627 million in 2025, its first full year on the market.
"Imdelltra has already revolutionised the standard of survival for patients with extensive-stage small cell lung cancer (搜索) whose disease progressed on or after prior treatment," said Jay Bradner, Amgen's R&D head. "These landmark results from DeLLphi-305 suggest Imdelltra will further revolutionise the standard for survival earlier in the treatment journey and meaningfully shift the treatment paradigm for people facing this devastating disease."
For AstraZeneca, the data offer the prospect of extending the Imfinzi label beyond its current uses in ES-SCLC — in combination with chemotherapy as a first-line therapy, and as maintenance therapy for limited-stage SCLC (LS-SCLC) in patients whose disease has not progressed following concurrent platinum-based chemo and radiation therapy (cCRT). Imfinzi has been approved by the FDA as a first-line treatment for ES-SCLC since 2020.
The Unmet Need in a Rapidly Relapsing Disease
Small cell lung cancer (搜索) remains one of the most aggressive forms of lung cancer, with limited treatment advances and poor long-term outcomes for many patients. Clinicians emphasized that the disease's rapid progression leaves little room for later-line therapy.
"Given the aggressive nature of small cell lung cancer (搜索), many patients quickly relapse on current therapy and never reach second-line treatment," said Jacob Sands, a thoracic oncology specialist at Dana-Farber Cancer Institute. "These patients do not have time to wait, making substantial progress in the first-line setting critically important. In my career treating people with extensive-stage small cell lung cancer (搜索), these are among the most compelling survival results I have seen."
Rajat Thawani, Assistant Professor at the Knight Cancer Institute at OHSU, noted that about 40% of these patients never reach second-line treatment. "The whole argument is that we should move what works earlier, and it looks like it landed," he said, adding that the hazard ratio will be important to assess whether maintenance can be adopted "without second thoughts."
Experts Await Mature Data and Detail
Commenting on the announcement, several oncologists welcomed the results while flagging outstanding questions. Gilberto Lopes, Chief of the Division of Medical Oncology at Sylvester Comprehensive Cancer Center, said the PFS and ORR findings were also positive but that "we still need the numbers: HR, median OS, subgroups and detailed safety. If the magnitude holds up, this could meaningfully change first-line ES-SCLC treatment."
Giannis Mountzios, Director of the 4th Oncology Department and Clinical Trials Unit at Henry Dunant Hospital Center, framed the result as a potential shift: "Time to move T-cell engagers to 1st-L maintenance? A new era is dawning for our patients with SCLC."
Mohit Manrao, SVP and Head of US Oncology at AstraZeneca, said the results "suggest a potential new approach to extending survival earlier in the treatment journey and represent an important step forward for the small cell lung cancer (搜索) community."
Access, Toxicity and Biomarker Questions
Beyond efficacy, specialists raised implementation challenges. Misty Shields, Assistant Professor at Indiana University School of Medicine, Indiana University Health, noted that tarlatamab was approved in the US for accelerated use in May 2024, yet patients globally still cannot access it in most countries outside of a trial. "Access: Progress only matters IF we can get therapies to those who need it," she said, asking how long first-line maintenance would take to implement and how equitable access could be provided.
Shields also pointed to the need for proactive management of T-cell engager toxicities, stating that cytokine release syndrome (CRS), ICANS and dysgeusia require aggressive multidisciplinary support to mitigate and manage. She further called for biomarker discovery beyond DLL3 (搜索) to identify who will benefit from intensification of first-line maintenance versus who could avoid potential time, treatment and financial toxicities.
Estela Rodriguez, Associate Director of Community Outreach-Thoracic Oncology at Sylvester Comprehensive Cancer Center, similarly highlighted questions around improving access, easing administration, refining patient selection and minimizing toxicity.
The DeLLphi-305 trial is registered as NCT06211036.