Dr Puri on Future Research Directions in SCLC

“It’s such an exciting time to be a researcher in small cell lung cancer. We are looking at more personalized treatments, more targets, and more innovative treatment approaches. [This includes] antibody-drug conjugates that have shown promising responses or are in development.”

Sonam Puri, MD, a thoracic oncologist and clinical medical director at Moffitt Cancer Center, discussed future research directions and ongoing developments in small cell lung cancer (SCLC).

Efforts to develop more personalized treatments and identify additional treatment targets are of great interest in SCLC, Puri began. For example, agents targeting delta-like ligand 3 (DLL3) and SEZ6 have shown promise in preclinical and early-phase trials, she noted. Radiopharmaceuticals are also being developed to interact with targets on the surface of SCLC tumor cells, she added. More sophisticated methods to engage T cells are being examined, including trispecific T-cell activating constructs, as well as approaches to engage other immune cells, Puri said.

During the 2025 ASCO Annual Meeting, multiple studies examining DLL3-targeted agents for the treatment of patients with SCLC were presented. Preliminary data from a phase 1 trial (NCT06179069) demonstrated that patients who received the DLL3-targeted antibody drug conjugate ZL-1310 (n = 28) achieved an overall response rate (ORR) of 68%, including a complete response (CR) rate of 4%. Findings from a phase 2 study (NCT06283719) showed that the DLL3/DLL3/CD3 trispecific T-cell engager alveltamig (ZG006) produced an ORR of 62.5% (95% CI, 40.6%-81.2%) and a disease control rate of 70.8% (95% CI, 48.9%-87.4%) among patients with refractory SCLC who received the agent at a dose of 10 mg every 2 weeks (n = 24).

Additionally, the ongoing phase 1/2 SKYBRIDGE study (NCT05652686) is examining the anti-DLL3/anti-CD47 bispecific antibody peluntamig (PT217) in patients with SCLC and other neuroendocrine carcinomas. The agent is designed to facilitate tumor cell attack via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. The study is presently enrolling patients at 9 sites across the US and comprises both monotherapy and combination cohorts.