The addition of tarlatamab-dlle (Imdelltra) to durvalumab (Imfinzi) resulted in a significant improvement in overall survival (OS) and progression-free survival (PFS) compared with durvalumab alone when used as first-line maintenance treatment in patients with extensive-stage small cell lung cancer (ES-SCLC) who did not progress after standard induction durvalumab plus platinum chemotherapy and etoposide, according to data from the planned interim analysis of the phase 3 DeLLphi-305 trial (NCT06211036).1
The doublet also resulted in a significantly improved objective response rate (ORR) vs the monotherapy. The toxicity profile of the combination regimen was in line with what has previously been reported with the individual agents, and no new safety signals were observed.
Full data are expected to be presented at a forthcoming medical meeting and shared with global regulatory authorities, according to a news release issued by AstraZeneca.
DeLLphi-305 in Frontline ES-SCLC Maintenance: Key Takeaways
- Durvalumab plus tarlatamab met the primary end point of OS at a planned interim analysis of the phase 3 DeLLphi-305 trial, marking the first survival benefit reported for an immunotherapy plus bispecific T-cell engager combination in this setting.
- The combination also significantly improved the secondary end points of PFS and ORR vs durvalumab alone in this population.
- Full findings from the trial are expected at a forthcoming medical meeting and will be shared with global regulators.
“Given the aggressive nature of [SCLC], many patients quickly relapse on current therapy and never reach second-line treatment. These patients do not have time to wait, making substantial progress in the first-line setting critically important,” Jacob Sands, MD, associate chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, in Boston, Massachusetts, stated in the news release. “In my career treating people with [ES-SCLC], these are among the most compelling survival results I have seen, indicating the potential 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.”
How was the DeLLphi-305 trial designed?
DeLLphi-305 is a phase 3, randomized, open-label, multicenter trial that enrolled 563 patients with ES-SCLC—including those with treated or untreated asymptomatic brain metastases—who had completed 3 to 4 cycles of investigator's choice of carboplatin or cisplatin and etoposide plus durvalumab as frontline induction without disease progression, which was defined as ongoing response or stable disease per RECIST 1.1 criteria.1-3 Eligible patients were 18 years or older with an ECOG performance status of 0 to 1, a minimum life expectancy of more than 12 weeks, and acceptable organ function.2
Participants were randomized 1:1 to durvalumab plus tarlatamab or durvalumab alone as maintenance until progression or unacceptable toxicity, with durvalumab dosed every 4 weeks and tarlatamab dosed every 2 weeks in the combination arm.2,3 After tarlatamab infusions on day 1 of cycle 1 and day 8 of cycle 1, patients were monitored in a healthcare setting for 1 to 2 hours; in certain regions, including Europe, they were monitored for 6 to 8 hours.1
The primary end point of the study is OS, and key secondary end points include PFS, ORR, disease control rate, and duration of response, each assessed by investigators per RECIST 1.1 criteria.2,3
In a recent OncLive Peer Exchange program, Sands and the rest of the expert panel—which was comprised of Joshua K. Sabari, MD; Anne Chiang, MD; Ticiana A. Leal, MD; and Misty D. Shields, MD, PhD—unpacked tarlatamab's unique mechanism as a bispecific T-cell engager linking DLL3 on tumor cells to CD3 on T cells, creating an antigen-directed immune response distinct from other therapeutic approaches.4
