Clinical potential of antibody-drug conjugates in early-phase clinical trials for late-line treatment of advanced solid tumors.

Abstract

Recently, comprehensive genomic profiling (CGP)-matched therapy and antibody-drug conjugates (ADCs) have garnered increased attention. However, their response rates and prognoses in early-phase clinical trials are not yet widely appreciated in clinical practice. We conducted a retrospective chart review of patients with advanced solid tumors who enrolled in clinical trials as a late-line treatment in our department between January 2020 and December 2023. This study aimed to evaluate clinical outcomes, including overall response rate (ORR), disease control rate (DCR), overall survival (OS), and associated prognostic factors. A total of 574 cases were referred, including 173 in the late-line setting. The ADCs group achieved the highest ORR and DCR (31.9% and 68.1%, respectively). ADCs also demonstrated a longer median progression-free survival (PFS) compared to CGP-matched and other trials (median PFS: ADCs 4.0 months vs. CGP-matched trials 1.9 months vs. others 1.7 months; p = 0.001). Multivariate analysis identified ADCs as significantly associated with improved PFS, while CGP-matched therapy was associated with better OS. The findings suggest that, even in early phase clinical trials for the late-line setting, ADCs can enhance therapeutic responses. These results underscore the need to avoid overreliance on CGP outcomes and instead prioritize early referral to Phase 1 facilities, timely intervention, and the appropriate inclusion of patients to achieve optimal clinical outcomes.