Dr Preeshagul on Emerging Treatments in SCLC

“[The FDA approvals of tarlatamab and durvalumab have] improved and enhanced [the SCLC treatment paradigm] because now we have options. It used to be chemotherapy, and then we’d [wait and] watch patients.”

Isabel Preeshagul, DO, MBS, a thoracic medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, discussed the role of emerging treatments in the small cell lung cancer (SCLC) landscape.

The SCLC landscape witnessed significant milestones in recent years, which has improved and enhanced the treatment paradigm, Preeshagul began. In May 2024, the FDA granted accelerated approval to tarlatamab-dlle (Imdelltra) for the treatment of patients with extensive-stage SCLC (ES-SCLC) who experienced disease progression on or after platinum-based chemotherapy. The regulatory decision was based on data from the phase 2 DeLLphi-301 trial (NCT05060016), which included 99 patients. Following tarlatamab, in December 2024, the FDA approved durvalumab (Imfinzi) after concurrent frontline chemoradiotherapy for the treatment of patients with limited-stage SCLC (LS-SCLC), which was supported by data from the phase 3 ADRIATIC trial (NCT03703297).

Previously, treatment for SCLC entailed chemotherapy and a wait-and-watch approach, Preeshagul continued. Specifically, she noted that topotecan was often given in the second-line setting before lurbinectedin was added to the toolbox of treatments. Nevertheless, there are now more options beyond chemotherapy, such as tarlatamab and durvalumab, which have further opened the door for additional agents, she explained. The approval of tarlatamab and the DeLLphi-301 study have emphasized the potential significance of DLL3, which could be an important marker in SCLC, Preeshagul concluded.

Results from the DeLLphi-301 study, published in The New England Journal of Medicine, revealed that the objective response rate (ORR) was 40% (95% CI, 31%-51%) and the median duration of response was 9.7 months (range, 2.7-20.7+) with tarlatamab. In patients with evaluable platinum-sensitivity status (n = 69), 27 patients had an ORR of 52% (95% CI, 32%-71%); patients with platinum-sensitive (n = 42) had an ORR of 31% (95% CI, 18%-47%). Tarlatamab also improved survival vs chemotherapy in the second-line treatment of patients with SCLC, according to data from the phase 3 DeLLphi-304 trial (NCT05740566) presented at the 2025 ASCO Annual Meeting.