City of Hope, one of the largest cancer research and treatment organizations in the United States, has secured a landmark contract worth up to $23.7 million from the Advanced Research Projects Agency for Health (ARPA-H) to develop a comprehensive biomap of tumor evolution and resistance mechanisms in advanced or metastatic non-small cell lung cancer (NSCLC). The initiative represents a paradigm shift toward adaptive precision oncology, moving away from static treatment protocols to dynamic therapeutic strategies that evolve with tumor biology.
Addressing Critical Treatment Gaps in Lung Cancer
NSCLC accounts for 87% of all lung cancer cases, affecting approximately 200,000 patients diagnosed annually in the United States. Current immunotherapy approaches face significant limitations, with existing biomarkers showing poor predictive reliability and patient response rates below 40%. The primary biomarker used to select immunotherapy, PD-L1 expression, has proven insufficient for guiding treatment decisions and predicting secondary resistance patterns.
"Changes in cancer may occur over time, creating resistance to immunotherapy and complicating oncologists' ability to identify the next best treatment approach," said Dr. Ravi Salgia, professor and chair of City of Hope's Department of Medical Oncology & Therapeutics Research and principal investigator of the study. "Developing a biomap that detects mutations and other alterations early and predicts a patient's cancer trajectory will enable us to match treatments to evolving tumor biology and improve our patients' long-term survival."
Revolutionary Clinical Trial Design
The cornerstone of this ambitious project is a six-year clinical trial enrolling 535 patients with advanced NSCLC. Unlike traditional cancer studies that focus on first-line therapy without flexibility for treatment modification, this trial is designed to adjust treatment strategies as resistance emerges. The research team aims to increase progression-free survival by 50% in at least one patient group through this adaptive approach.
City of Hope's Beckman Research Institute researchers will employ state-of-the-art diagnostic techniques including liquid biopsies, single-cell sequencing, and radiomic imaging to monitor tumor trajectory and patient response in near real-time. The methodology encompasses serial sample collection and detailed data gathering at regular intervals throughout the treatment course, providing unprecedented resolution of tumor heterogeneity and immune microenvironment dynamics.
"Instead of measuring a few data types at a single timepoint with limited predictive ability, the ADAPT program will take many measurements of diverse data over time and through multiple lines of treatments," explained Dr. Aritro Nath, City of Hope assistant professor with the Division of Molecular Pharmacology. "The insights gleaned will help identify newly acquired resistant traits in tumors, predict the right therapies at each point in a patient's treatment and identify strategies that provide better long-term prognoses."
Multi-Dimensional Biomarker Integration
The project will integrate multi-parametric data including genomic, transcriptomic, proteomic, and imaging information to create a comprehensive, temporally resolved biomap reflecting tumor adaptive states. This approach contrasts sharply with current practices that rely on limited biomarkers with poor predictive power.
Dr. Jyoti Malhotra, associate professor and interim division chief of Thoracic Medical Oncology at City of Hope, emphasized the clinical significance: "We expect our collaboration with ADAPT will uncover predictive biomarkers that will enhance patient treatment and boost immunotherapy responses in non-small cell lung cancer. The information we gather will allow for informed adjustments in treatments and improve patient outcomes."
National Impact and Data Sharing
The trial leverages City of Hope's extensive network of more than 35 clinical sites whose populations reflect the nation's lung cancer patients, ensuring broad generalizability of findings. Patient enrollment is anticipated to begin within 12 months, with the research team planning swift mobilization of resources and expertise.
Importantly, algorithms and aggregate datasets developed under the program will be made publicly available, enabling scientists worldwide to visualize trends and evaluate implications in near real-time. This open-science approach is designed to accelerate global cancer research and foster collaborative innovation.
Part of Broader ARPA-H Initiative
City of Hope's project operates within ARPA-H's Advanced Analysis for Precision Cancer Therapy (ADAPT) program, a $142 million initiative combining cutting-edge technologies with national expertise in tumor biology to deliver customized cancer care that adapts to evolving disease states. The program represents a coordinated effort to decode cancer's evolving biology and tailor treatments to the mutable nature of tumor ecosystems.
Dr. Salgia, who oversees more than 130 medical oncologists including a nationwide team of 30 clinicians dedicated to lung cancer, brings over 30 years of experience in clinical trials and translational research. His leadership has been instrumental in uncovering key variants in lung cancer, positioning City of Hope at the forefront of this transformative research initiative.
"We are incredibly excited to launch this ambitious project," said Dr. Salgia. "Our analysis of host and tumor biology will help clinicians counter the limits of current treatment choices and lead to better patient management strategies for advanced and metastatic non-small cell lung cancer."
