Fresh off the excitement of Rasonque’s big splash in pancreatic cancer, the oncology community has another impressive clinical win to celebrate. Amgen’s T-cell engager Imdelltra has posted a massive survival benefit in small cell lung cancer, delivering what Chief Medical Officer Paul Burton, M.D., Ph.D., called a “watershed moment” for the field.
When added on top of AstraZeneca’s Imfinzi, Imdelltra reduced the risk of death by 58% as a first-line maintenance therapy for patients with extensive-stage SCLC who had not progressed following initial treatment with Imfinzi and chemotherapy.
The result came from the phase 3 DeLLphi-305 study, which showed that, compared with Imfinzi alone, Imdelltra plus Imfinzi improved median overall survival by 8.4 months to 21.1 months. These data are being presented during a presidential symposium at the European Society for Medical Oncology Congress 2026 and simultaneously published in The New England Journal of Medicine.
“I think we are at a true watershed moment in the management of small cell lung cancer,” Burton said in an interview with Fierce, labeling Imdelltra’s unprecedented trial results “transformational” for SCLC patients.
Besides the huge OS benefit, the Imdelltra regimen also lowered the risk of disease progression or death by 66% versus Imfinzi alone, with a median progression-free survival length of 7.4 months versus 1.9 months.
Burton likened Imdelltra’s SCLC data to the massive wave Revolution Medicines’ Rasonque made earlier this year in pancreatic cancer. Fueled by a 60% death risk reduction in the phase 3 RASolute 302 trial, Rasonque generated huge buzz in the oncology community and scored an expedited FDA approval in August.
In a separate interview with Fierce, AZ’s oncology R&D chief, Susan Galbraith, Ph.D., also alluded to a Rasonque comparison, noting that the current five-year survival rate of ES-SCLC is even lower than pancreatic ductal adenocarcinoma.
Moreover, Burton suggested that the survival benefit observed in DeLLphi-305 so far may actually understate Imdelltra’s true power, as the data were drawn from an interim analysis with a median follow-up of about 16 months.
The Amgen exec pointed to an updated analysis from the DeLLphi-303 phase 1b study, which tested Imdelltra either with Imfinzi or Roche’s Tecentriq as first-line maintenance therapy. With a median follow-up of 30.8 months, median overall survival reached 37.9 months, according to Amgen. At two years, 58.1% of patients remained alive.
Burton indicated that, with longer follow-up, the large DeLLphi-305 trial will show a similar survival benefit for Imdelltra as the two studies’ OS curves are “almost superimposable.”
For a difficult-to-treat cancer type in which patients’ real-world median OS currently ranges from eight months to a little over 10 months, what Imdelltra has shown across the two trials is transformational, he said.
Imdelltra’s striking data cast a long shadow over Jazz Pharmaceuticals’ Zepzelca. The Jazz chemotherapy expanded into the ES-SCLC first-line maintenance setting after showing its addition to Roche’s Tecentriq reduced the risk of death by 27%. In the phase 3 IMforte trial, the Zepzelca-Tecentriq regimen recorded a median OS of 13.2 months, versus 10.6 months for Tecentriq alone.
Imdelltra’s success also marks a major breakthrough for T-cell engagers, which need to overcome an immunosuppressive tumor microenvironment and immune side effects to work in solid tumors.
T-cell engagers, when used on their own, can cause the T cells to become exhausted. The addition of Imfinzi, a PD-L1 checkpoint inhibitor, helps rein in that mechanism and drive more durable responses, AZ’s Galbraith explained.
Burton described Imdelltra’s safety profile as “very manageable and […] very tolerable.” Even though half of patients in the Imdelltra-Imfinzi arm experienced cytokine release syndrome (CRS), only one (0.4%) reached grade 3, while the rest were managed by simple measures such as steroids.
Immune effector cell-associated neurotoxicity syndrome, or ICANS, only happened in three (1.1%) patients, with no grade 3 or above events.
Because of the risks of early-onset CRS and ICANS, Imdelltra reached the market in previously treated SCLC initially with a recommendation that patients be followed for 22 to 24 hours during their first two infusions. The FDA recently cut that monitoring time to 6 to 8 hours. And in DeLLphi-305, Amgen tested just 1 to 2 hours of monitoring.
“That comfort and confidence with the safety profile is mirrored by the fact that we can now offer patients shorter and shorter monitoring,” Burton said.
Overall, grade 3 or higher treatment-related adverse events (TRAEs) occurred in 20.9% of patients treated with Imdelltra-Imfinzi and 10.8% of those who got Imfinzi alone. Decrease in neutrophil count (3.2%), decreased appetite (2.1%) and neutropenia (2.1%) are among the most common grade 3 or greater TRAEs.
Late-line cancer patients have more exhausted T cells, which could explain why T-cell engagers confer better treatment effects in earlier treatment settings, Burton said.
As Imdelltra has conquered first-line maintenance ES-SCLC, Amgen is already evaluating the drug in combination with Imfinzi and chemo as a first-line induction and maintenance therapy in the phase 3 DeLLphi-312 trial. Another phase 3 trial, DeLLphi-306, will see if Imdelltra works following concurrent chemoradiotherapy in limited-stage SCLC.
Imdelltra’s current second-line label covers about 13,000 patients in the U.S. If those studies pan out, the drug could address a population of 35,000 to 40,000 patients, Burton noted.
But Imdelltra’s success as the first DLL3-targeted agent has fueled competitor interest in the target. These include Zai Lab’s DLL3 antibody-drug conjugate, zocilurtatug pelitecan (zoci). Early phase 1 data has linked zoci, used on top of Tecentriq, to an 81.8% confirmed ORR and an 81.9% six-month PFS rate in 33 patients, according to data shared at ESMO 2026.
Following the readout, Citi analysts said zoci is “increasingly well-positioned [...] to become a chemo-sparing backbone in SCLC for future frontline I/O and TCE combinations.”
AbbVie, Merck & Co., Novartis and Roche are also among biopharma companies circling DLL3 in various modalities.
Meanwhile, an emerging class of B7-H3 ADCs, which includes GSK’s Hansoh Pharma-partnered risvutatug rezetecan (ris-rez), could also become a force to be reckoned with in SCLC, as could the sizzling hot PD-(L)1xVEGF group. BioNTech is already exploring pairing its Bristol Myers Squibb-partnered PD-L1xVEGF bispecific pumitamig with its Duality Biologics-teamed B7-H3 candidate elfetabart drozuntecan (elfe-D) and has shown some impressive early tumor response data.
Despite a rapidly changing drug development landscape, Burton expressed confidence in Imdelltra’s future role.
“I would predict that Imdelltra will become the indispensable backbone therapy for the management of small cell lung cancer,” the Amgen exec said. “I think there are other intriguing and attractive targets. We’re exploring combination therapies as well.”
While viewed as direct competitors because of their shared DLL3 target, Imdelltra and zoci are being explored as a combination in an early-stage study sponsored by Amgen.