A groundbreaking blood test has emerged, revealing a crucial indicator that could significantly influence treatment decisions for lung cancer patients. Researchers from the Mass General Brigham Cancer Institute have identified a specific marker found on tumor cells circulating within the bloodstream, which can predict whether individuals suffering from lung cancer will respond positively to a newly approved immunotherapy known as tarlatamab. This pivotal research, published in the journal Cancer Discovery, holds the promise of enabling doctors to determine, in a straightforward and non-invasive manner, which patients are most likely to benefit from this innovative drug.
Dr. Daniel A. Haber, MD, PhD, who serves as the director of the Krantz Family Center for Cancer Research at the Mass General Brigham Cancer Institute, emphasized the potential of isolating cancer cells from blood samples. He stated, "The ability to extract these cells offers immense possibilities for guiding cancer therapies that harness the immune system, and we have pioneered advanced bioengineering techniques to effectively purify these circulating tumor cells. Although we have made significant strides in understanding the biology of these cells, we previously lacked a clinical test with direct relevance. We believe our current study has bridged that gap." Notably, the technology developed for enriching these blood cells has been licensed to TellBio, Inc., indicating its commercial potential.
The primary focus of this study was to explore how characteristics of circulating tumor cells might relate to a patient’s response to tarlatamab, which received full approval in late 2025 for treating small cell lung cancer (SCLC) after prior chemotherapy treatments. Tarlatamab functions as an antibody that engages T cells to target cancer cells exhibiting a specific neuro-endocrine marker known as DLL3.
Despite showing promise during clinical trials, it was observed that approximately fifty percent of SCLC patients encountered cancer progression within six months after beginning treatment with tarlatamab. Initially, it was assumed that all SCLC cases would express DLL3; however, Dr. Haber and his team discovered through their research that only half of the 20 patients examined had high levels of DLL3-positive cancer cells in their blood. These patients were the ones who exhibited a favorable response to tarlatamab. Their findings demonstrated that testing for DLL3 on circulating tumor cells accurately identified 85% of patients who benefited from the medication, while also achieving a perfect specificity rate of 100% for those who did not respond (85% sensitivity and 100% specificity).
This study represents a collaborative effort between experts in bioengineering, who developed the technology to analyze rare cancer cells present in blood samples, and clinicians focused on lung cancer treatment, highlighting its significant implications for patient care.
Dr. Justin Gainor, MD, who is the program director at the Center for Thoracic Cancers at the Mass General Brigham Cancer Institute and co-corresponding author of the study, remarked, "Our research may assist in predicting which SCLC patients are most likely to respond to tarlatamab, and potentially other antibodies aimed at DLL3, many of which are currently under development. Additionally, this has potential ramifications for other cancers exhibiting DLL3 expression as these cancers become increasingly aggressive, and it could further impact the realm of antibody-directed cancer therapies."
The authors of this important work include prominent researchers such as Avanish Mishra, Catherine B. Meadord, Kruthika Kikkeri, and several others from Mass General Brigham.
It's worth noting that Toner, Haber, and Maheswaran are co-founders of TellBio, a biotechnology firm actively commercializing the CTC-iChip technology utilized in this research. Further disclosures regarding the authors can be accessed in the published paper.
Funding for this pivotal study was sourced from various grants, including those from the Novartis-MGH Research Alliance, the National Institutes of Health, and the Conquer Cancer Foundation of the American Society of Clinical Oncology, among others.
For those interested in the detailed findings, the complete study can be referenced as follows: Mishra A, Meador CB, Kikkeri K, et al. "Circulating Tumor Cells Predict Response to the DLL3-targeting Bispecific Antibody Tarlatamab" Cancer Discovery DOI: 10.1158/2159-8290.CD-25-1483.
