A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti–PD-1 Agent Pembrolizumab
Abstract
Malignant pleural diseases, comprising metastatic lung and breast cancers and malignant pleural mesothelioma (MPM), are aggressive solid tumors with poor therapeutic response. We developed and conducted a first-in-human, phase I study of regionally delivered, autologous, mesothelin-targeted chimeric antigen receptor (CAR) T-cell therapy. Intrapleural administration of 0.3M to 60M CAR T cells/kg in 27 patients (25 with MPM) was safe and well tolerated. CAR T cells were detected in peripheral blood for >100 days in 39% of patients. Following our demonstration that PD-1 blockade enhances CAR T-cell function in mice, 18 patients with MPM also received pembrolizumab safely. Among those patients, median overall survival from CAR T-cell infusion was 23.9 months (1-year overall survival, 83%). Stable disease was sustained for ≥6 months in 8 patients; 2 exhibited complete metabolic response on PET scan. Combination immunotherapy with CAR T cells and PD-1 blockade agents should be further evaluated in patients with solid tumors.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 15, 2021
- Source ID
- 10.1158/2159-8290.cd-21-0407
Entities
People
- Alain Vincent
- Amy Zhu
- Bobby Daly
- Brigitte Senechal
- Charles Rudin
- Claudia Diamonte
- Daniel Ngai
- David R Jones
- Devanjan Sikder
- Elizabeth Halton
- Erin Mcgee
- Isabelle Rivière
- Jennifer L Sauter
- John Pineda
- Jose A. Araujo Filho
- Kay See Tan
- Marjorie Zauderer
- Michel Sadelain
- Mithat Gönen
- Navin K. Chintala
- Prasad S Adusumilli
- Renier J. Brentjens
- Rocio Perez-Johnston
- Roisin E. O'Cearbhaill
- Shanu Modi
- Stephen B. Solomon
- Valerie W. Rusch
- Waseem Cheema
- William D. Travis
- Xiuyan Wang
Organizations
- Memorial Sloan Kettering Cancer Center
- National Institutes of Health
- United States Department of Defense