Immunomodulatory Activity of a Colony-Stimulating Factor-1 Receptor Inhibitor in Patients With Advanced Refractory Breast or Prostate Cancer: A Phase 1 Study.
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.
|Authors:||Autio KA, Klebanoff CA, Schaer DA, Kauh JS, Slovin SF, Adamow M, Blinder V, Brahmachary M, Carlsen M, Comen E, Danila DC, Doman TN, Durack JC, Fox JJ, Gluskin JS, Hoffman DMJ, Kang S, Kang P, Landa J, McAndrew P, Modi S, Morris MJ, Novosiadly RD, Rathkopf|
|Journal:||Clin. Cancer Res.;2020 Nov 1;26(21):5609-5620. doi:10.1158/1078-0432.CCR-20-0855|
|PubMed:||PMID: 32847933 (Go to PubMed)|