A combination of AstraZeneca’s Imfinzi (durvalumab) and Amgen’s Imdelltra (tarlatamab) have 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.
In the Phase III, open-label DeLLphi-305 study (NCT06211036), the pair assessed the efficacy and safety of Imfinzi-Imdelltra as a maintenance treatment – specifically in patients with frontline ES-SCLC who didn’t progress after induction treatment with an Imfinzi-chemotherapy combination.
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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.
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.
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, with researchers observing no new safety signals linked to their use in tandem.
Following the positive outcome of the DeLLphi-305 study, AstraZeneca and Amgen plan to share these data with global regulatory authorities.
If this combination secures approval, it could offer an enhanced commercial opportunity for Amgen in lung cancer – moving 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.
Influencing the SoC in ES-SCLC
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.
According to Jacob Sands, associate chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, progress in the frontline SCLC setting is crucial, as many patients quickly relapse after initial treatment and never reach second-line options.
In his eyes, the DeLLphi-305 results are among the “most compelling” survival results he’s seen – indicating the potential of Imfinzi-Imdelltra to “reshape the natural history of SCLC.”
“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 added.
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.
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.
