Abstract
INTRODUCTION: Immunotherapy has revolutionized the treatment of NSCLC. However, trials that led to approval of these agents and ongoing trials often include overly included overly restrictive exclusion criteria, limiting access for a significant proportion of patients. We propose the immunotherapy clinical trial inclusivity score (ICTIS), a scoring system to evaluate trial eligibility criteria for inclusivity. METHODS: ICTIS was developed using national guidelines and validated with a Cohen's Kappa statistics of 0.807. Eligibility criteria for advanced NSCLC immunotherapy trials on ClinicalTrials.gov were scored using a binary scale (0 = exclusive, 1 = inclusive), with higher summed scores indicating higher inclusivity. Mean ICTIS scores were compared across lines of treatment, start date, and trial phase. RESULTS: The mean ICTIS score among 142 trials was 12.7 (SD 4), with 28 trials (19.7%) rated as excellent and 34 trials (23.9%) rated poor. The most restrictive criteria were Eastern Cooperative Oncology Group performance status (78.8%), organ function criteria of bilirubin (76.1%), and absolute neutrophil count (65.5%). First-line trials were significantly more exclusive to patients with pneumonitis history, with 64% exclusion versus 45.5% in second-line (χ(2) = 4.917, p = 0.027). The platelet count requirement was more stringent in monotherapy trials. Inclusion of treated leptomeningeal disease improved over time (χ(2) = 7.99, p = 0.018), but eligibility criteria remained consistent across different time periods, lines of treatment, and trial phases. CONCLUSIONS: Despite the release of national guidelines, immunotherapy trials have overall retained restrictive eligibility criteria. ICTIS provides a standardized framework for evaluating inclusivity and can assist in designing immunotherapy studies to be more inclusive.