A combination of AstraZeneca’s Imfinzi (durvalumab) and Amgen’s Imdelltra (tarlatamab) has been shown to significantly boost patient outcomes versus Imfinzi alone in a Phase III extensive-stage small cell lung cancer (ES-SCLC) trial, which analysts say could pave the way to a new frontline standard of care (SoC) for the condition.
Trial Results Show Promise
The Phase III, open-label DeLLphi-305 study (NCT06211036) assessed the efficacy and safety of Imfinzi-Imdelltra as a maintenance treatment. Specifically, it involved patients with frontline ES-SCLC who had not progressed after induction treatment with an Imfinzi-chemotherapy combination. During the trial, patients given the combination experienced a statistically significant improvement in overall survival (OS) over those who received Imfinzi alone, meeting the trial’s primary endpoint. The study design focused on a population that had already demonstrated a response to initial platinum-based chemotherapy and subsequent immunotherapy consolidation, evaluating whether the addition of a bispecific T-cell engager could prolong the time before the disease progresses further.
Alongside its ability to improve OS, researchers identified Imfinzi-Imdelltra’s potential to significantly boost progression-free survival (PFS) and objective response rates (ORR) compared with Imfinzi as a monotherapy, leading the drug to hit two of its secondary endpoints. These secondary outcomes are critical in oncology trials as they provide a more granular view of how quickly tumors shrink or stop growing, offering patients valuable interim benefits while waiting for the ultimate survival data to mature. The combination’s mechanism allows for the redirection of T-cells directly to the tumor site, potentially amplifying the body’s own immune defenses in a way that a single-agent therapy might not achieve.
Patients also tolerated the combination of Imfinzi, a PD-L1-targeting immunotherapy, and Imdelltra, a DLL3 x CD3 bispecific T-cell engager (BiTE), similarly to each drug alone. Researchers observed no new safety signals linked to their use in tandem. The manageable safety profile observed in this maintenance setting is particularly encouraging, as it suggests that the risks associated with the therapy do not compound when administered sequentially rather than simultaneously. This observation is vital for establishing a new standard of care, as patient adherence to long-term maintenance regimens often depends on the tolerability of the treatment regimen.
Regulatory Next Steps
Following the positive outcome of the DeLLphi-305 study, AstraZeneca and Amgen plan to share these data with global regulatory authorities. The sharing of full efficacy and safety data is a necessary step toward seeking marketing authorizations that will allow the combination to be prescribed for this specific patient population. Regulatory bodies will scrutinize the magnitude of benefit relative to existing standards, making the detailed statistical breakdowns a focal point of the submission process.
If this combination secures approval, it could offer an enhanced commercial opportunity for Amgen in lung cancer. This would move Imdelltra from its current place in the second-line therapeutic paradigm into the frontline setting. Currently, GlobalData analysts forecast peak sales of more than $10bn and $3bn for Imfinzi and Imdelltra, respectively, within the 2026-2032 forecast period. Expanding into the frontline space would not only increase the total addressable market for Imdelltra but also create a broader portfolio cooperation with Imfinzi, which is already established in the maintenance setting.
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While multiple new targeted therapies have now made it to market in SCLC, the aggressive nature of this type of cancer means it remains hard to treat. Progress in the frontline SCLC setting is critical, as many patients quickly relapse after initial treatment and never reach second-line options. The high relapse rate shows the urgent need for effective maintenance strategies that can keep the disease at bay for extended periods, turning a terminal diagnosis into a manageable chronic condition for some.
Expert Reaction and Impact
According to Jacob Sands, associate chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, the DeLLphi-305 results are among the “most compelling” survival results he has seen. Sands indicated the potential of Imfinzi-Imdelltra to “reshape the natural history of SCLC.” He added, “DeLLphi-305 represents an unprecedented milestone and suggests we may be entering a new era where meaningfully longer survival is possible for more patients.” Sands’ perspective highlights the profound clinical impact that improved survival metrics can have on patient prognosis and quality of life.
Meanwhile, Philip Hart, consulting director at GlobalData-owned Deallus, notes that Imdelltra’s win in the solid tumour maintenance setting is an interesting signal. However, he is waiting to see full data—including “medians, hazard ratios and especially subgroups such as platinum sensitivity, brain metastases, DLL3 expression and performance status”—to determine whether Imfinzi-Imdelltra will become the default or a more selected option. Hart’s cautionary approach reflects the subtle reality of clinical decision-making, where subgroup analyses often reveal that a drug works better in specific patient subsets than in the broader population.
In the eyes of analysts at William Blair, while neither Amgen nor AstraZeneca has disclosed numerical results form DeLLphi-305, prior data and stopping at an interim suggest that Imdelltra will “likely set a new standard of care” in the frontline ES-SCLC setting.
They added that a reduced monitoring requirement of one-to-two hours after the first two infusions with favourable safety, compared with the 22-24 hours as laid out on the US prescription label, could pave the way for potential label modifications – potentially making Imdelltra’s uptake in the frontline setting easier. The practical considerations of administration, such as the length of time a patient must remain under observation post-infusion, are often decisive factors in the adoption of new biologics and targeted therapies.
