Outlining Next Steps for Tarlatamab in Early-Line ES-SCLC and Beyond

Using bispecific T-cell engagers (BiTEs) like tarlatamab-dlle (Imdelltra) in earlier lines of extensive-stage small cell lung cancer (ES-SCLC) treatment, in patients with limited-stage SCLC, and in combination with other standard SCLC therapies are among the next steps for further researching this treatment modality, according to Daniel R. Carrizosa, MD, MS.

CancerNetwork® spoke with Carrizosa, associate professor of Cancer Medicine at Wake Forest University School of Medicine, associate program director of the Hematology/Oncology Fellowship at Levine Cancer Institute/Carolinas Medical Center, and senior assistant director of Community Outreach & Engagement at Wake Forest Baptist Comprehensive Cancer Center, about efficacy findings supporting the approval of tarlatamab in patients with ES-SCLC.¹ He also discussed other novel advancements in T-cell engagers and next steps for researching BiTEs in lung cancer and beyond.

Highlighting its May 2024 approval in ES-SCLC, he pointed to data from the phase 3 DeLLphi-304 trial (NCT05740566) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, which showed that tarlatamab produced a median overall survival (OS) of 13.6 months vs 8.3 months with chemotherapy (HR, 0.60; 95% CI, 0.47-0.77; P <.001).² According to Carrizosa, this outcome, along with advantageous response and progression-free survival (PFS) data, support tarlatamab’s use as the standard of care in second-line SCLC.

Furthermore, he outlined other advancements in T-cell engagers, touching upon tri-specifics showing promising safety and efficacy. Another area of interest, he suggested, included identifying targets and biomarkers beyond lung cancer, with sarcoma and uveal melanoma both having approved bispecifics.

He concluded by expressing that although tarlatamab is solely approved for use in the second line, he hopes that the agent could move into earlier lines of therapy, as well as other SCLC indications. Finally, he explained that tarlatamab is currently being investigated with checkpoint inhibitors, with considerations for use with antibody drug conjugates or other therapies in the future.

Transcript:

Tarlatamab was approved by the FDA in 2024 based on the DeLLphi studies, most recently DeLLphi-304, [which] was presented at ASCO 2025. This showed that there was a survival advantage of over 5 months between tarlatamab and our standard of care in the second line. This also had a good durable response and [PFS], and it is therefore now considered [the] standard of care in second-line SCLC.

Tarlatamab is the first in probably a long line of new therapies that are coming out in SCLC and, eventually, in other types of cancers. Tarlatamab is being used because of its bispecifics, but multiple other companies are also looking at [BiTEs]. There are also tri-specific T-cell constructs that are also being studied; some of them have also recently been reported at ASCO, showing responses and efficacy. We are looking to see if we can find newer biomarkers and targets outside of [SCLC] and lung cancer. Currently, uveal melanoma also has a bispecific that is approved, as well as sarcoma. This is only the beginning for a whole new line of therapies for solid tumors.

Currently, tarlatamab is only approved in the second line. It has this efficacy in a disease that has few treatment options that do not last long. The hope is to move this up in its treatment area, to either the maintenance phase, hopefully the first-line area, or even the limited-stage SCLC [area], which is our curable area. We also are trying to see if we can add this to checkpoint inhibitors that are currently standard in SCLC. Then, the question would be other [combinations], such as antibody drug conjugates or other types of therapies that may be used in conjunction with tarlatamab.

References

1. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. News release. FDA. May 16, 2024. Accessed July 30, 2025. https://tinyurl.com/48k34rw5
2. Rudin CM, Mountzios GS, Sun L, et al. Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): primary analysis of ph3 DeLLphi-304. J Clin Oncol. 2025;43(suppl 17):8008. doi:10.1200/JCO.2025.43.17_suppl.LBA8008