Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors
Background To determine the safety and efficacy of the anti-colony-stimulating factor 1 receptor (anti-CSF1R) monoclonal antibody AMG 820 in combination with pembrolizumab in patients with select solid tumors.Patients and methods Patients had advanced, refractory mismatch repair-proficient colorecta...
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doaj-c86d4e961e1c408ea5c8168b4d7c83df2021-07-13T15:01:37ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-07-018210.1136/jitc-2020-001006Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumorsAlbiruni RA Razak0James M Cleary1Michael Boyer2Emiliano Calvo Aller3William Edenfield4R Donald Harvey5Annemie Rutten6David P Ryan7Hansen Wong8Neelesh Soman9Marie-Anne Damiette Smit10Division of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, CanadaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USADepartment of Medical Oncology, Chris O’Brien Lifehouse, Camperdown, New South Wales, AustraliaEarly Phase Clinical Drug Development in Oncology, START Madrid - CIOCC, Centro Integral Oncológico Clara Campal, Madrid, SpainPrisma Health Institute for Translational Oncology Research, Greenville, South Carolina, USADepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University Hospital, Atlanta, Georgia, USAGasthuisZusters Antwerpen Sint-Augustinus, Antwerp, BelgiumDepartment Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts, USAAmgen Inc, South San Francisco, California, USAAmgen Inc, Thousand Oaks, California, USAAmgen Inc, Thousand Oaks, California, USABackground To determine the safety and efficacy of the anti-colony-stimulating factor 1 receptor (anti-CSF1R) monoclonal antibody AMG 820 in combination with pembrolizumab in patients with select solid tumors.Patients and methods Patients had advanced, refractory mismatch repair-proficient colorectal cancer, pancreatic cancer, or non-small cell lung cancer (NSCLC) with low (<50%) programmed cell death-ligand 1 (PD-L1) expression and were naïve to anti-programmed cell death-1 (PD-1)/PD-L1 or had relapsed/refractory NSCLC after anti-PD-1/PD-L1 treatment with low or high (≥50%) PD-L1 expression; all were anti-CSF1/CSF1R naïve. Patients received 1100 mg or 1400 mg AMG 820 plus 200 mg pembrolizumab intravenously every 3 weeks. The primary endpoints were incidence of dose-limiting toxicities (DLTs) and adverse events (AEs) and objective response rate per immune-related Response Evaluation Criteria in Solid Tumours at the recommended combination dose.Results Overall, 116 patients received ≥1 dose of AMG 820 plus pembrolizumab (18 at 1400 mg AMG 820; 98 at 1100 mg AMG 820). Most patients (64%) were male; the median age was 64 (range 30–86) years. Seven patients had DLTs (1 at 1400 mg AMG 820; 6 at 1100 mg AMG 820). Almost all patients (99.1%) had AEs, 87.9% with grade ≥3 AEs. The most common AEs were increased aspartate aminotransferase (59.5%), fatigue (48.3%), periorbital/face edema (48.3%), and rash/maculopapular rash (37.1%). The best response was immune-related partial response in 3 patients (3%; duration of response 9.2, 10.0, 12.5 months) and immune-related stable disease in 39 patients (34%). None of the completed phase II cohorts met the predefined threshold for efficacy. Post-treatment there was accumulation of serum colony-stimulating factor 1 (CSF1) and interleukin-34, reduction in CSF1-dependent CD16-expressing monocytes, and increased PD-L1 expression and CD4 and CD8 cell numbers in tumor biopsies.Conclusions The recommended combination dose of 1100 mg AMG 820 plus 200 mg pembrolizumab had an acceptable safety profile. Although pharmacodynamic effects were observed, antitumor activity was insufficient for further evaluation of this combination in selected patient populations.Trial registration number NCT02713529https://jitc.bmj.com/content/8/2/e001006.full |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Albiruni RA Razak James M Cleary Michael Boyer Emiliano Calvo Aller William Edenfield R Donald Harvey Annemie Rutten David P Ryan Hansen Wong Neelesh Soman Marie-Anne Damiette Smit |
spellingShingle |
Albiruni RA Razak James M Cleary Michael Boyer Emiliano Calvo Aller William Edenfield R Donald Harvey Annemie Rutten David P Ryan Hansen Wong Neelesh Soman Marie-Anne Damiette Smit Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors Journal for ImmunoTherapy of Cancer |
author_facet |
Albiruni RA Razak James M Cleary Michael Boyer Emiliano Calvo Aller William Edenfield R Donald Harvey Annemie Rutten David P Ryan Hansen Wong Neelesh Soman Marie-Anne Damiette Smit |
author_sort |
Albiruni RA Razak |
title |
Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors |
title_short |
Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors |
title_full |
Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors |
title_fullStr |
Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors |
title_full_unstemmed |
Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors |
title_sort |
safety and efficacy of amg 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors |
publisher |
BMJ Publishing Group |
series |
Journal for ImmunoTherapy of Cancer |
issn |
2051-1426 |
publishDate |
2020-07-01 |
description |
Background To determine the safety and efficacy of the anti-colony-stimulating factor 1 receptor (anti-CSF1R) monoclonal antibody AMG 820 in combination with pembrolizumab in patients with select solid tumors.Patients and methods Patients had advanced, refractory mismatch repair-proficient colorectal cancer, pancreatic cancer, or non-small cell lung cancer (NSCLC) with low (<50%) programmed cell death-ligand 1 (PD-L1) expression and were naïve to anti-programmed cell death-1 (PD-1)/PD-L1 or had relapsed/refractory NSCLC after anti-PD-1/PD-L1 treatment with low or high (≥50%) PD-L1 expression; all were anti-CSF1/CSF1R naïve. Patients received 1100 mg or 1400 mg AMG 820 plus 200 mg pembrolizumab intravenously every 3 weeks. The primary endpoints were incidence of dose-limiting toxicities (DLTs) and adverse events (AEs) and objective response rate per immune-related Response Evaluation Criteria in Solid Tumours at the recommended combination dose.Results Overall, 116 patients received ≥1 dose of AMG 820 plus pembrolizumab (18 at 1400 mg AMG 820; 98 at 1100 mg AMG 820). Most patients (64%) were male; the median age was 64 (range 30–86) years. Seven patients had DLTs (1 at 1400 mg AMG 820; 6 at 1100 mg AMG 820). Almost all patients (99.1%) had AEs, 87.9% with grade ≥3 AEs. The most common AEs were increased aspartate aminotransferase (59.5%), fatigue (48.3%), periorbital/face edema (48.3%), and rash/maculopapular rash (37.1%). The best response was immune-related partial response in 3 patients (3%; duration of response 9.2, 10.0, 12.5 months) and immune-related stable disease in 39 patients (34%). None of the completed phase II cohorts met the predefined threshold for efficacy. Post-treatment there was accumulation of serum colony-stimulating factor 1 (CSF1) and interleukin-34, reduction in CSF1-dependent CD16-expressing monocytes, and increased PD-L1 expression and CD4 and CD8 cell numbers in tumor biopsies.Conclusions The recommended combination dose of 1100 mg AMG 820 plus 200 mg pembrolizumab had an acceptable safety profile. Although pharmacodynamic effects were observed, antitumor activity was insufficient for further evaluation of this combination in selected patient populations.Trial registration number NCT02713529 |
url |
https://jitc.bmj.com/content/8/2/e001006.full |
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