A research team has discovered that a particular marker on circulating tumor cells (CTCs) may indicate whether a patient with small cell lung cancer (SCLC) will experience a lasting response to tarlatamab-dlle, a newly approved immunotherapy. The findings, which were published by Mishra in Cancer Discovery, may allow clinicians to easily and noninvasively determine which patients should receive the drug.
“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 [CTCs],” 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. “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.”
The study focused on whether properties of CTCs might correlate with a patient’s response to tarlatamab, which was fully approved by the U.S. Food and Drug Administration in November 2025 as a treatment for adult patients with extensive-stage SCLC whose disease progressed on or after receiving platinum-based chemotherapy. Tarlatamab is an antibody that recruits T cells to cancer cells expressing a specific neuroendocrine marker called DLL3.
Although tarlatamab showed promise in clinical trials, about half of patients with SCLC experience disease progression within 6 months of initiating therapy. It was thought that every SCLC case expresses DLL3, but Dr. Haber and colleagues found that only half of the 20 patients they studied had abundant DLL3-positive cancer cells in their blood—and these were the patients who responded to tarlatamab. DLL3 testing on CTCs correctly identified 85% of patients who had a clinical benefit from the drug and 100% who did not (85% sensitivity, 100% specificity).
The study—which was a collaboration between bioengineering experts who had developed the technology to analyze rare cancer cells in blood specimens and lung cancer clinicians—has important implications for clinical care.
“Our work may help predict which patients with SCLC are likely to respond to tarlatamab and potentially other antibodies targeting DLL3, 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. “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.”
DISCLOSURE: The blood cell enrichment technology has been licensed to TellBio, Inc. For full disclosures of the study authors, visit aacrjournals.org/cancerdiscovery.
