- 2026-01-23
- Cancer 132(3)
- Yiyang Shan
- Bo Ding
- Feng Ji
- Hao Lin
- Weiwei Shi
- Enxiu Wang
- Chen Wang
- Yang Shen
Study Design
- Type
- Clinical Trial
- Population
- 11 patients with advanced ovarian cancer
- Methods
- First-in-human, dose-escalation trial of KT127 with rapid titration and 3+3 design, doses 1×10^6 to 2×10^7 cells/kg after lymphodepletion
- Funding
- Unclear
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.