| Autor: |
Heather L. McArthur, Phillip Wong, Danni Yu, Courtney M. Tate, Sonya C. Chapman, Rachel Sanford, Dana E. Rathkopf, Ruslan Novosiadly, Michael J. Morris, Shanu Modi, Philomena F. McAndrew, Jonathan Landa, Praneet Kang, Suhyun Kang, David M. Hoffman, Jill S. Gluskin, Josef J. Fox, Jeremy C. Durack, Thompson N. Doman, Daniel C. Danila, Elizabeth Comen, Michelle Carlsen, Manisha Brahmachary, Victoria S. Blinder, Matthew Adamow, Susan F. Slovin, John Sae Wook Kauh, David Schaer, Christopher A. Klebanoff, Karen A. Autio |
| Rok vydání: |
2023 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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