Emerging ADCs in SCLC: Spotlight on B7-H3 and MHB088C

Biomarkers in small cell lung cancer (SCLC) present complex challenges, particularly when it comes to antibody-drug conjugates (ADCs). Unlike other cancers where PD-L1 expression can guide immunotherapy decisions, PD-L1 has proven to be an unreliable marker in SCLC. Emerging targets such as B7-H3 and DLL3 show promise, but the relationship between target expression and treatment response is not straightforward. Although DLL3 is widely expressed in SCLC tumors, response rates to DLL3-targeted therapies remain modest. This discrepancy may be due to tumor heterogeneity, changes in biomarker expression over time, and reliance on archival tissue samples that may not reflect the current tumor biology. Therefore, there is a growing need for longitudinal biomarker monitoring through noninvasive methods like plasma assays to better understand the dynamics of these targets.

The development of targeted therapies in SCLC is still in its early stages, with many parallels to the evolution seen in non–small cell lung cancer (NSCLC) treatments over the past 2 decades. Just as multiple generations of EGFR inhibitors have emerged through ongoing research, the understanding of biomarkers like DLL3, B7-H3, and others will likely improve, leading to more effective therapies. Clinical trials play a crucial role in this process, offering patients access to cutting-edge treatments and providing essential data to advance the field. Increasing equitable access to these trials is vital, especially for historically underrepresented populations, ensuring that progress benefits all patients and not just a select few.

Despite the excitement around ADCs, platinum doublet chemotherapy remains the first-line standard of care due to its high initial response rate, particularly important for patients with a heavy disease burden. However, studies are underway to explore combinations of ADCs with immunotherapy or even to replace components of the platinum regimen. These efforts aim to improve efficacy while potentially reducing toxicity. While replacing platinum doublet chemotherapy is a high bar, ongoing research and trial participation may soon shift current treatment paradigms, offering new hope for patients with SCLC.