Immunomodulatory activity of a colony-stimulating factor-1 receptor inhibitor in patients with advanced refractory breast or prostate cancer: A phase I study Journal Article
| Authors: | Autio, K. A.; Klebanoff, C. A.; Schaer, D.; Kauh, J. S. W.; Slovin, S. F.; Adamow, M.; Blinder, V. S.; Brahmachary, M.; Carlsen, M.; Comen, E.; Danila, D. C.; Doman, T. N.; Durack, J. C.; Fox, J. J.; Gluskin, J. S.; Hoffman, D. M.; Kang, S.; Kang, P.; Landa, J.; McAndrew, P. F.; Modi, S.; Morris, M. J.; Novosiadly, R.; Rathkopf, D. E.; Sanford, R.; Chapman, S. C.; Tate, C. M.; Yu, D.; Wong, P.; McArthur, H. L. |
| Article Title: | Immunomodulatory activity of a colony-stimulating factor-1 receptor inhibitor in patients with advanced refractory breast or prostate cancer: A phase I 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 I study evaluated the immunologic and clinical activity, and safety profile of CSF-1R inhibition with the mAb LY3022855. Patients and Methods: 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 2 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; patients with MBC 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 proinflammatory monocytes CD14DIMCD16BRIGHT decreased. Best RECIST response was stable disease in five patients with MBC (23%; duration, 82-302 days) and three patients with mCRPC (25%; duration, 50-124 days). Two patients with MBC (cohort A) had durable stable disease >9 months and a third patient with MBC had palpable reduction in a nontarget neck mass. Immune-related gene activation in tumor biopsies posttreatment 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 patients with MBC. © 2020 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 26 |
| Issue: | 21 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2021-11-01 |
| Start Page: | 5609 |
| End Page: | 5620 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-20-0855 |
| PUBMED: | 32847933 |
| PROVIDER: | scopus |
| PMCID: | PMC8519606 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2021 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work