Tremelimumab in Combination with Exemestane in Patients with Advanced Breast Cancer and Treatment-Associated Modulation of Inducible Costimulator Expression on Patient T Cells

摘要: Purpose: Tremelimumab is a fully human monoclonal antibody specific for CTL-associated antigen 4 (CTLA4) with single-agent activity in certain tumors but has not been evaluated patients breast cancer. Experimental Design: In phase 1 study, 26 advanced, hormone-responsive cancer received tremelimumab (3-10 mg/kg) every 28 days or 90 plus exemestane 25 mg daily. The objectives were to determine safety and the maximum tolerated dose (MTD) of and, secondarily, assess tumor response, pharmacokinetics, immune pharmacodynamics. Results: Most treatment-related adverse events mild moderate most common being diarrhea (46% patients), pruritus (42%), constipation (23%), fatigue (23%). Dose-limiting toxicities transient serum transaminase elevations (one patient) (four patients). MTD was 6 mg/kg days. Among 13 treated at MTD, none developed grade 3 diarrhea. No pharmacokinetic interaction observed between exemestane. best overall response stable disease ≥12 weeks 11 (42%). Treatment associated increased peripheral CD4+ CD8+ T cells expressing inducible costimulator (ICOS) marked increase ratio ICOS+ FoxP3+ regulatory cells. Conclusions: tolerable advanced cells, which likely signals activation secondary blockade. Clin Cancer Res; 16(13); 3485–94. ©2010 AACR.