ICTIS: A Novel Scoring System to Assess the Inclusivity of Advanced NSCLC Immunotherapy Trials

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.

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.

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 (χ² = 4.917, p = 0.027). The platelet count requirement was more stringent in monotherapy trials. Inclusion of treated leptomeningeal disease improved over time (χ² = 7.99, p = 0.018), but eligibility criteria remained consistent across different time periods, lines of treatment, and trial phases.

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.