Dr Halmos on Novel Targets for Drug Development in SCLC

"We're hoping for a lot more [advancements in] extensive-stage SCLC. It's been welcome news to understand a bit more of the biology and the different kind of molecular subsets of s SCLC, but also the important critical functional value of certain molecules such as DLL3."

Balazs Halmos, MD, professor, Department of Oncology (Medical Oncology), professor, Department of Medicine (Oncology & Hematology), associate director, Clinical Science, Montefiore Einstein Comprehensive Cancer Center, discusses novel targets for drug development in small cell lung cancer (SCLC).

Recent advances in immunotherapy have brought welcome news for patients with SCLC; however, challenges remain in treating extensive-stage SCLC (ES-SCLC), Halmos begins. Although immune checkpoint inhibitors have become an essential addition to the treatment armamentarium in limited-stage SCLC (LS-SCLC), their affect on outcomes in ES-SCLC has been more limited, he explains. Accordingly, there is renewed focus on improving understanding of disease biology in ES-SCLC, especially the role of molecules like DLL3, Halmos states. DLL3 has emerged as a potential treatment target, and DLL3-targeted bispecific antibody T-cell engagers (BiTEs) in development have shown early activity and, in some cases, durable responses, he reports.

Although the development of BiTEs has been a key advancement in SCLC, it also introduces new challenges, Halmos notes. Adverse effects associated with these therapies, such as cytokine release syndrome and neurotoxicity, may be unfamiliar to those used to managing solid tumors. These novel therapies require careful management and a learning curve for clinical practice, he says.

In addition to BiTE molecules, antibody-drug conjugates (ADCs) are also of interest in SCLC, Halmos continues. B7-H3–directed ADCs are particularly exciting, as they have demonstrated significant clinical benefit with response rates of approximately 50%, he details. These agents are gaining traction, and their relative tolerability makes them more suitable for integration into community practice. As clinical development continues, ADCs could become an important part of the treatment repertoire for SCLC, offering another option for patients with limited treatments, Halmos concludes.