Autio et al. report the safety and clinical activity of an anti-CSF-1 receptor antibody (LY3022855) in patients with metastatic breast and castration-resistant prostate cancer (MBC and mCRPC). LY3022855 increased the levels of circulating CSF-1 and IL-34, and reduced circulating proinflammatory CD14DIMCD16BR monocytes. Out of 34 treated patients, 5 MBC and 3 mCRPC patients showed SD. Two MBC patients showed durable SD for over 9 months. Patients with SD had an increase in circulating LAG3+CD4+ and LAG3+CD8+ T cells and intratumoral immune activation-related gene expression. No unexpected treatment related adverse effects were seen.
Contributed by Shishir Pant
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 ³1 dose of LY3022855. At Day 8, circulating CSF_1 levels increased and pro-inflammatory monocytes CD14(DIM)CD16(BRIGHT) 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.
Author Info: (1) Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center/Weill Cornell Medical College autiok@mskcc.org. (2) Center for Cell Engineering,
Author Info: (1) Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center/Weill Cornell Medical College autiok@mskcc.org. (2) Center for Cell Engineering, Memorial Sloan Kettering Cancer Center. (3) Oncology Translational Research, Pfizer. (4) Clinical Development, Hutchison MediPharma. (5) Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center. (6) Medicine, Memorial Sloan Kettering Cancer Center. (7) Immigrant Health and Cancer Disparities, Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center. (8) Oncology Research, Eli Lilly and Company. (9) Eli Lilly and Company. (10) Medicine, Memorial Sloan Kettering Cancer Center. (11) Medicine(Genitourinary Oncology Service), Memorial Sloan Kettering Cancer Center. (12) Oncology Bioinformatics, Eli Lilly and Company. (13) Radiology, Memorial Sloan Kettering Cancer Center. (14) Radiology, Memorial Sloan-Kettering. (15) Radiology, Memorial Sloan Kettering Cancer Center/Weill Cornell Medical College. (16) Medical Oncology, Cedars-Sinai Medical Center. (17) Eli Lilly and Company. (18) Memorial Sloan Kettering Cancer Center. (19) Radiology, Memorial Sloan Kettering Cancer Center. (20) Cedars-Sinai Medical Center. (21) Medicine, Memorial Sloan-Kettering Cancer Center/Weill Cornell Medical College. (22) Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College. (23) Translational Medicine, Bristol-Myers Squibb (United States). (24) Memorial Sloan Kettering Cancer Center/Weill Cornell Medical College. (25) Memorial Sloan Kettering Cancer Center/Weill Cornell Medical College. (26) Global PK/PD, Eli Lilly and Company. (27) Lilly Research Laboratories, Eli Lilly and Company. (28) Oncology, Eli Lilly and Company. (29) Immunology, Memorial Sloan Kettering Cancer Center. (30) Breast Medical Oncology, Cedars-Sinai Medical Center.
