Cancer. 2026 Feb 1;132(3):e70279. doi: 10.1002/cncr.70279.
ABSTRACT
BACKGROUND: Ovarian cancer remains a formidable therapeutic challenge due to late diagnosis, high recurrence rates, and limited treatment options. Mesothelin (MSLN) is highly expressed in ovarian cancer, making it a promising target for immunotherapy. Given this target profile, the authors developed a novel T-cell receptor (TCR)-like chimeric antigen receptor (CAR) T-cell therapy targeting MSLN, designated KT127.
METHODS: A first-in-human, dose-escalation trial of KT127 was conducted following preclinical evaluation in vitro and in vivo. A combination of rapid titration and a standard «3 + 3» dose-escalation design was implemented. Eleven patients received KT127 at doses ranging from 1 × 106 to 2 × 107 cells/kg following lymphodepletion. The primary objectives were to assess the safety and tolerability of KT127. Secondary objectives included overall survival, disease control rate (DCR), and progression-free survival as efficacy measures. Quality of life (QOL) was assessed using the European Organisation for Research and Treatment of Cancer QLQ-OV28 questionnaire.
RESULTS: No dose-limiting toxicities, cytokine release syndrome, or immune effector cell-associated neurotoxicity syndrome were observed. The DCR was 80% (95% confidence interval, 44.4%-97.5%). QOL assessments indicated improvement in abdominal/gastrointestinal symptoms post-treatment (p = .037), with no significant deterioration in other domains. Proteomic analysis identified differential expression of kallikrein-related peptidases (KLK13, KLK14) and chemokine CXCL17 at baseline, potentially linked to treatment outcomes.
CONCLUSIONS: This study highlights that KT127 has a manageable safety profile and shows preliminary biological activity in patients with advanced ovarian cancer, particularly those who have failed multiple lines of therapies.
PMID:41575866 | DOI:10.1002/cncr.70279
