Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Immunomodulatory Activity of a Colony-Stimulating Factor-1 Receptor Inhibitor in Patients With Advanced Refractory Breast or Prostate Cancer: A Phase 1 Study.

Abstract

PURPOSE: Tumor-associated macrophages correlate with increased invasiveness, growth, and immunosuppression. Activation of the colony-stimulating factor-1 receptor (CSF-1R) results in proliferation, differentiation, and migration of monocytes/macrophages. This Phase 1 study evaluated the immunologic and clinical activity, and safety profile of CSF-1R inhibition with the monoclonal antibody LY3022855. EXPERIMENTAL DESIGN: Patients with advanced refractory metastatic breast cancer (MBC) or metastatic castration-resistant prostate cancer (mCRPC) were treated with LY3022855 intravenously in 6-week cycles in cohorts: A) 1.25 mg/kg every two weeks (Q2W); B) 1.0 mg/kg on Weeks 1, 2, 4, and 5; C) 100 mg once weekly; D)100 mg Q2W. mCRPC patients were enrolled in Cohorts A and B; MBC patients were enrolled in all cohorts. Efficacy was assessed by RECIST and Prostate Cancer Clinical Trials Working Group 2 criteria. RESULTS: Thirty-four patients (22 MBC; 12 mCRPC) received >=1 dose of LY3022855. At Day 8, circulating CSF-1 levels increased and pro-inflammatory monocytes CD14DIMCD16BRIGHT decreased. Best RECIST response was stable disease in five MBC patients (23%; duration 82-302 days) and three mCRPC patients (25%; duration 50-124 days). Two MBC patients (Cohort A) had durable stable disease >9 months and a third MBC patient had palpable reduction in a nontarget neck mass. Immune-related gene activation in tumor biopsies post-treatment was observed. Common any grade treatment-related adverse events were fatigue, decreased appetite, nausea, asymptomatic increased lipase, and creatine phosphokinase. CONCLUSIONS: LY3022855 was well tolerated and showed evidence of immune modulation. Clinically meaningful stable disease >9 months was observed in two MBC patients.