Amgen has detailed a positive phase 3 readout for its T-cell engager Imdelltra in previously treated small cell lung cancer (SCLC).
The DLL3xCD3 bispecific has shown that it can help patients live longer, has a more tolerable safety profile and improves certain cancer-related symptoms compared with chemotherapy in second-line SCLC, according to results from the phase 3 DeLLphi-304 trial. The data will be presented June 2 at the 2025 American Society of Clinical Oncology annual meeting and simultaneously published in The New England Journal of Medicine.
The drug significantly reduced the risk of death by 40% versus chemo in SCLC patients who had tried one line of platinum-based chemotherapy. Patients in the Imdelltra arm lived a median 13.6 months, compared with 8.3 months for chemo.
All patient subgroups appeared to have benefited, regardless of their prior PD-1/L1 exposure, presence of brain metastases or liver metastases, and the type of prior chemotherapy. Among those who had tried a PD-1/L1 inhibitor, Imdelltra’s death risk reduction was 39%. In PD-1/L1-naïve patients, the number was 35%.
“These data underscore Imdelltra’s potential to transform patient outcomes and the small cell lung cancer treatment paradigm,” Amgen’s R&D chief, Jay Bradner, M.D., said in a statement.
Findings from the DeLLphi-304 trial could help convert Imdelltra’s accelerated approval earned last year into a full approval.
Besides hitting its overall survival endpoint at the planned interim analysis, the DeLLphi-304 trial also showed other benefits for Imdelltra.
Imdelltra was linked to a 29% lower risk of disease progression or death compared with chemotherapy. The median progression-free survival time was 4.2 months and 3.7 months, respectively.
The rate of grade 3 or higher treatment-related adverse events was notably lower among Imdelltra takers, at 27%, than in the 62% recorded in the chemotherapy group. Three percent of patients in the Imdelltra group discontinued treatment due to adverse events, whereas the number was 6% in the control arm.
On cytokine release syndrome (CRS), a known side effect of T-cell engagers, Imdelltra recorded no grade 4 or 5 events, and grade 3 cases only occurred in 1% of patients. All told, CRS occurred in 56% of Imdelltra patients.
On another side effect of interest for T-cell immunotherapies, immune effector cell-associated neurotoxicity syndrome (ICANS), Imdelltra saw one (0.4%) death.
“The patient’s death was attributed to ICANS in the context of progressive neurologic decline concurrent with persistent fever, hypoxemia and hypotension,” the study’s investigators wrote in the NEJM article.
All the other 14 (5.6%) ICANS cases in the Imdelltra arm were grade 1 or 2.
Treatment with Imdelltra also resulted in significantly better outcomes for cancer-related symptoms of shortness of breath and cough, according to prespecified analyses of patient-reported changes at Week 19.
However, although data favored Imdelltra, the difference in chest pain score between the two arms was not significant. As a result, physical functioning and global health status were not formally tested.
Amgen currently has three phase 3 trials running or being planned for Imdelltra in first-line SCLC. They are DeLLphi-305 for Imdelltra and AstraZeneca’s Imfinzi as a first-line maintenance treatment for extensive-stage SCLC, DeLLphi-306 for Imdelltra in first-line maintenance limited-stage SCLC, and DeLLphi-312, in which Amgen plans to add Imdelltra to chemo and Imfinzi in extensive-stage SCLC.
Imdelltra’s success has sparked much interest in DLL3 as a target. Also at ASCO 2025, Legend Biotech reported preliminary efficacy results of a phase 1 study of LB2102, a DLL3-targeted CAR-T candidate being partnered with Novartis.
Legend reported no dose-limiting toxicities up to the highest dose of LB2102 tested and observed better tumor shrinkage results as the dose went higher, according to an abstract covering nine patients who received one of three dose levels of the therapy. Although the data were limited, researchers suggested further exploration of higher dose levels is warranted.
Novartis in 2023 paid Legend $100 million upfront to work on DLL3-targeted CAR-T candidates including LB2102.