Blood Test Identifies Small Cell Lung Cancer Patients Who Will Respond to Tarlatamab Immunotherapy
Key Insights
Mass General Brigham researchers developed a blood test that predicts which small cell lung cancer patients will benefit from tarlatamab, a newly approved immunotherapy targeting DLL3 (search)-positive cancer cells.
The test analyzes circulating tumor cells for DLL3 (search) expression and demonstrated 85% sensitivity and 100% specificity in identifying patients who would clinically benefit from the drug.
Only half of the 20 patients studied had abundant DLL3 (search)-positive cancer cells in their blood, and these were the patients who responded to tarlatamab treatment.
Investigators at the Mass General Brigham Cancer Institute (search) have developed a blood test that can predict which patients with small cell lung cancer (SCLC) will respond to tarlatamab, a newly approved immunotherapy. The research, published in Cancer Discovery, offers a noninvasive method to identify patients most likely to benefit from the drug before treatment begins.
Novel Biomarker Discovery
The study focused on analyzing circulating tumor cells (CTCs) in blood samples to determine their correlation with patient response to tarlatamab. Tarlatamab, which received full approval in late 2025 for treating SCLC after prior chemotherapy, is an antibody that recruits T cells to cancer cells expressing the neuro-endocrine marker DLL3 (search).
"Isolating cancer cells from the blood has tremendous potential to guide immune-related cancer therapies, and our group has created cutting edge bioengineering technologies for purification of these circulating tumor cells," said senior and co-corresponding author Daniel A. Haber, MD, PhD, director of the Krantz Family Center for Cancer Research at the Mass General Brigham Cancer Institute (search). "We've learned a lot about the biology of these cells, but we haven't had a test that has direct clinical relevance. In this study, we believe that we achieved this."
Clinical Performance and Implications
The research team studied 20 patients and discovered that only half had abundant DLL3 (search)-positive cancer cells in their blood. Significantly, these were the patients who responded to tarlatamab treatment. The DLL3 testing on CTCs demonstrated impressive clinical performance, correctly identifying 85% of patients who had a clinical benefit from the drug and 100% of those who did not, achieving 85% sensitivity and 100% specificity.
This finding challenges the previous assumption that every SCLC case expresses DLL3 (search). The discovery is particularly important given that approximately half of patients with SCLC experience cancer progression within six months of initiating tarlatamab therapy, despite the drug's promise in clinical trials.
Broader Therapeutic Applications
The research has implications beyond tarlatamab treatment. "Our work may help predict which patients with SCLC are likely to respond to tarlatamab and potentially other antibodies targeting DLL3 (search), many of which are in development," said co-corresponding author Justin Gainor, MD, program director of the Center for Thoracic Cancers at the Mass General Brigham Cancer Institute (search). "It also has potential implications for other cancers that express DLL3 as they become more aggressive and for the field of antibody-directed cancer therapies."
Technology Transfer and Future Development
The blood cell enrichment technology underlying this breakthrough has been licensed to TellBio, Inc. (search), indicating potential for commercial development. The study represents a collaboration between bioengineering experts who developed the technology to analyze rare cancer cells in blood specimens and lung cancer clinicians, highlighting the interdisciplinary approach needed for such innovations.
The research offers a practical solution to a significant clinical challenge in SCLC treatment, potentially allowing clinicians to make more informed treatment decisions and improve patient outcomes through personalized therapy selection.