Phase I study of local radiation and tremelimumab in patients with inoperable locally recurrent or metastatic breast cancer.

Phase I study of local radiation and tremelimumab in patients with inoperable locally recurrent or metastatic breast cancer. Oncotarget. 2019 Apr 26;10(31):2947-2958 Authors: Jiang DM, Fyles A, Nguyen LT, Neel BG, Sacher A, Rottapel R, Wang BX, Ohashi PS, Sridhar SS Abstract Immunotherapy has shown modest activity in metastatic breast cancer (MBC). In this phase I dose escalation study, we assessed safety of tremelimumab, a humanized anti-CTLA4 monoclonal antibody, at starting dose 3 mg/kg, on the third day of palliative radiotherapy (2000cGy in 5 daily fractions) in patients with MBC. Primary objective was to determine the maximum tolerated dose (MTD) of tremelimumab combined with RT. Secondary objective was to assess response. Among 6 patients enrolled between July 2010 and October 2011, 5 had hormone receptor-positive MBC, 1 had triple negative MBC. Median age was 45 years. Common toxicities included lymphopenia (83%), fatigue (50%) and rash (33%). One dose-limiting toxicity occurred at 6 mg/kg, however the trial closed before MTD could be determined. One patient discontinued treatment due to a pathological fracture. Best response was stable disease (SD), 1 patient had SD for >6 months. Median follow up was 27.0 months. Median OS was 50.8 months, with 1 patient surviving >8 years. Peripheral blood mononuclear cell (PBMC) profiles showed increasing proliferating (Ki67+) Treg cells 1 week post treatment in 5 patients. Overall,...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research