Molecular Response Adaptive Immuno-Chemotherapy in Patients With NSCLC

In Partnership with Cancer Research Institute (2019-PRESENT)

Valsamo Anagnostou, MD, PhD, Johns Hopkins University

Valsamo Anagnostou, MD, PhD

Lung cancer is the leading cause of cancer-related deaths worldwide. Systemic therapy is generally indicated for patients who present with metastases (stage IV) or recur following initial first-line treatment. Disease management goals for patients with advanced non-small cell lung cancer (NSCLC), the most common type of lung cancer, are to prolong survival, maintain quality of life, and minimize side effects due to treatment.

While immune checkpoint therapy is effective for certain subsets of lung cancer patients, optimal management of individual patients treated with these immune-based therapies is complicated by challenges including high costs as well as complex interpretation of imaging data meant to inform on therapeutic response, side effects, and resistance. Limitations associated with conventional radiologic imaging in assessing patient response to immune checkpoint inhibition highlight an urgent need for novel biomarkers that are more precise and that can be measured more rapidly. Development of a such biomarkers will maximize clinical benefit by quickly identifying patients who should continue on immune checkpoint therapy, while reducing both the monetary and time costs for non-responding patients who should be moved to an alternative therapy.

The Cancer Research Institute (CRI) and The Mark Foundation for Cancer Research (MFCR) have launched a first-of-its-kind phase 2, multi-center clinical trial that aims to demonstrate the utility of a novel, ultra-sensitive, circulating tumor DNA (ctDNA) biomarker-directed blood test, or liquid biopsy, in assessing NSCLC patient responses to immunotherapy. Non-invasive liquid biopsy approaches have the potential to accurately and rapidly predict therapeutic response to immune checkpoint blockade, supporting future implementation within standard immune checkpoint treatment schema to inform on and drive more efficient treatment decisions.

published research

Anagnostou V, Ho C, Nicholas G, Juergens RA, Sacher A, Fung AS, Wheatley-Price P, Laurie SA, Levy B, Brahmer JR, Balan A, Niknafs N, Avrutin E, Zhu L, Sausen M, Bradbury PA, O’Donnell-Tormey J, Gaudreau PO, Ding K, Dancey J. ctDNA response after pembrolizumab in non-small cell lung cancer: phase 2 adaptive trial results. Nat Med. 2023.

Kelly RJ, Landon BV, Zaidi AH, Singh D, Canzoniero JV, Balan A, Hales RK, Voong KR, Battafarano RJ, Jobe BA, Yang SC, Broderick S, Ha J, Marrone KA, Pereira G, Rao N, Borole A, Karaindrou K, Belcaid Z, White JR, Ke S, Amjad AI, Weksler B, Shin EJ, Thompson E, Smith KN, Pardoll DM, Hu C, Feliciano JL, Anagnostou V, Lam VK. Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses. Nat Med. 2024.