PT  - JOURNAL ARTICLE
AU  - Autio, Karen A.
AU  - Klebanoff, Christopher A.
AU  - Schaer, David
AU  - Kauh, John Sae Wook
AU  - Slovin, Susan F.
AU  - Adamow, Matthew
AU  - Blinder, Victoria S.
AU  - Brahmachary, Manisha
AU  - Carlsen, Michelle
AU  - Comen, Elizabeth
AU  - Danila, Daniel C.
AU  - Doman, Thompson N.
AU  - Durack, Jeremy C.
AU  - Fox, Josef J.
AU  - Gluskin, Jill S.
AU  - Hoffman, David M.
AU  - Kang, Suhyun
AU  - Kang, Praneet
AU  - Landa, Jonathan
AU  - McAndrew, Philomena F.
AU  - Modi, Shanu
AU  - Morris, Michael J.
AU  - Novosiadly, Ruslan
AU  - Rathkopf, Dana E.
AU  - Sanford, Rachel
AU  - Chapman, Sonya C.
AU  - Tate, Courtney M.
AU  - Yu, Danni
AU  - Wong, Phillip
AU  - McArthur, Heather L.
TI  - Immunomodulatory Activity of a Colony-stimulating Factor-1 Receptor Inhibitor in Patients with Advanced Refractory Breast or Prostate Cancer: A Phase I Study
AID  - 10.1158/1078-0432.CCR-20-0855
DP  - 2020 Nov 01
TA  - Clinical Cancer Research
PG  - 5609--5620
VI  - 26
IP  - 21
4099  - http://clincancerres.aacrjournals.org/content/26/21/5609.short
4100  - http://clincancerres.aacrjournals.org/content/26/21/5609.full
SO  - Clin Cancer Res2020 Nov 01; 26
AB  - 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.