Dr Alder on Time-of-Day Impact on Tarlatamab Infusions for SCLC

With BiTEs, we probably have a little bit more of that signal just because of that T-cell efficacy, and we know that circadian rhythms can affect immune biology. With ADCs, there is some bystander effect and maybe some immune activation, but I think it's much less.

In the second segment of an interview at the IASLC 2026 World Conference on Lung Cancer (WCLC) in Seoul, Laura Alder, MD, assistant professor of medicine, Division of Medical Oncology, discussed a multicenter retrospective analysis of time of day of tarlatamab (Imdelltra) infusion and outcomes in small cell lung cancer (SCLC).

Alder and colleagues presented a retrospective analysis of 58 patients with SCLC treated with tarlatamab at Duke University and the University of North Carolina between June 2024 and October 2025. Building on evidence that early-day administration of immune checkpoint inhibitors may enhance T-cell activation, the investigators hypothesized that early time-of-day infusion (8 AM to 3 PM) during cycle 1 would improve outcomes.

Patients were grouped by the number of early infusions received on cycle 1 day 1 and day 8: none (n = 14), 1 (n = 24), or 2 (n = 20); all patients received the day 15 dose in the early window. Baseline characteristics, including median age (67 years), ECOG performance status of 0 or 1 (78%), and prior lines of therapy (median, 1), were balanced across groups.

Contrary to the hypothesis, early infusion was not associated with better outcomes. Objective response rates were 35.7%, 29.2%, and 20.0% for 0, 1, and 2 early doses, respectively, with disease control rates of 57.1%, 54.2%, and 40.0%.

Median progression-free survival (PFS) was 8.82, 3.38, and 2.10 months, and median overall survival (OS) was not reached, 14.66 months, and 8.46 months. Cytokine release syndrome occurred in 21.4%, 58.3%, and 30.0% of patients, and immune effector cell–associated neurotoxicity syndrome in 21.4%, 20.8%, and 35.0%.

Alder was direct about the scope of the work: the poster is not practice changing, she said, but the question was clinically interesting and worth asking. Even with balanced groups, she noted, subtle differences in disease burden and patient characteristics, including liver metastases, which are associated with higher CRS risk, and brain metastases, which were present in roughly 90% of each group, could influence the result and would need to be fully accounted for.

The next step, in her view, is a larger retrospective cohort to see whether the same signal holds. If it does, a randomized trial could follow, and its design would have to settle how to define early versus late infusion and whether the 8 AM to 3 PM window used here should be narrowed.

On biology, Alder said bispecific T-cell engagers are the class most likely to show a time-of-day effect because their activity depends on T-cell function, and circadian influence on immune biology has been demonstrated in several studies. Antibody-drug conjugates, which act mainly through payload delivery and bystander effect with comparatively little immune activation, would be expected to show much less signal, she said.

Alder said she would be interested to know whether ongoing trials of bispecific and trispecific T-cell engagers are capturing infusion time, which would allow the question to be examined in far larger populations.