Uncovering Subsequent Research Considerations for Tarlatamab in ES-SCLC

Biomarker research, different formulations, and modified dose schedules are among the next steps for evaluating tarlatamab-dlle (Imdelltra) as a second-line treatment option for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC). Bingnan Zhang, MD, MBA, an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed these considerations and more among the aforementioned patient group in a conversation with CancerNetwork®.

Zhang explained that numerous active clinical trials are exploring multiple avenues for tarlatamab research, including for a subcutaneous formulation to better mitigate common toxicities, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), among this patient population, different dose schedules, and optimizing tarlatamab by moving it to an outpatient setting. Next, she emphasized that biomarker research is warranted, given a 35% response rate among patients with ES-SCLC, despite DLL3, which tarlatamab binds to, being present in 80% of patients. This research would help identify why some patients experience a short-term response or none.

Finally, she discussed combination strategies for tarlatamab, including with cytotoxic agents, such as chemotherapy, and antibody drug conjugates, which she claimed are a new class of drugs for patients with SCLC, as well as strategies for bolstering the immune system over the course of treatment.

Transcript:

There is a lot of research ongoing, even for tarlatamab. There are ongoing clinical trials testing different formulations of tarlatamab. The subcutaneous formulation may have lower toxicity for CRS and ICANS, and that’s an active clinical trial. Also, exploring different dosing schedules; right now, it's every 2 weeks. Also, potentially moving it to an outpatient regimen, so optimizing the tarlatamab medication itself.

In terms of improving patient outcomes and for better efficacy long-term, we need biomarker research to figure out which patients are more likely to derive benefit and response–to have a durable response to tarlatamab– because DLL3 as a target is widely present in patients [with SCLC]; about 80%. The response rate to tarlatamab is around 40%. There is a subset of patients that can derive long-term benefit, but there’s also a substantial percentage who may not respond at all or have a short-term response.

One aspect is to figure out how to better select this treatment to match patients who are most likely to respond, and learning mechanisms of resistance and why patients are not responding to [tarlatamab]. We can come up with rational combination therapies, either combining different cytotoxic agents like chemotherapy or antibody drug conjugates, which are a new class of agents coming to the treatment of the [SCLC] paradigm, or figuring out a way to make the immune system more responsive or less exhausted over the course of tarlatamab treatment. These are all active areas of translational and biomarker research.

Reference

Mountzios G, Sun L, Cho BC, et al. Tarlatamab in small-cell lung cancer after platinum-based chemotherapy. N Engl J Med. 2025;393(4):349-361. doi:10.1056/NEJMoa2502099