TY - JOUR
T1 - Immunomodulatory activity of a colony-stimulating factor-1 receptor inhibitor in patients with advanced refractory breast or prostate cancer
T2 - A phase I study
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.
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.
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.
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U2 - 10.1158/1078-0432.CCR-20-0855
DO - 10.1158/1078-0432.CCR-20-0855
M3 - Article
C2 - 32847933
AN - SCOPUS:85100911786
SN - 1078-0432
VL - 26
SP - 5609
EP - 5620
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 21
ER -