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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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001006.full |
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| author | Jeanne Tie Dirk Jäger Victor Moreno Dirk Nagorsen Gloria Juan Kyriakos P Papadopoulos Anthony J Olszanski Erik Rasmussen Nehal Lakhani Albiruni RA Razak James M Cleary Michael Boyer Emiliano Calvo Aller William Edenfield R Donald Harvey Annemie Rutten Manish A Shah David P Ryan Hansen Wong Neelesh Soman Marie-Anne Damiette Smit |
| author_facet | Jeanne Tie Dirk Jäger Victor Moreno Dirk Nagorsen Gloria Juan Kyriakos P Papadopoulos Anthony J Olszanski Erik Rasmussen Nehal Lakhani Albiruni RA Razak James M Cleary Michael Boyer Emiliano Calvo Aller William Edenfield R Donald Harvey Annemie Rutten Manish A Shah David P Ryan Hansen Wong Neelesh Soman Marie-Anne Damiette Smit |
| author_sort | Jeanne Tie |
| collection | DOAJ |
| 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 |
| format | Article |
| id | doaj-art-c86d4e961e1c408ea5c8168b4d7c83df |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-c86d4e961e1c408ea5c8168b4d7c83df2024-11-10T02:05:07ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/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 tumorsJeanne Tie0Dirk Jäger1Victor Moreno2Dirk Nagorsen3Gloria Juan4Kyriakos P Papadopoulos5Anthony J Olszanski6Erik Rasmussen7Nehal Lakhani8Albiruni RA Razak9James M Cleary10Michael Boyer11Emiliano Calvo Aller12William Edenfield13R Donald Harvey14Annemie Rutten15Manish A Shah16David P Ryan17Hansen Wong18Neelesh Soman19Marie-Anne Damiette Smit207 Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, AustraliaDepartment of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Heidelberg, Germany3 Consortium for Biomedical Research in Epidemiology and Public Health, CIBERESP, Madrid, Spain12Affini-T Therapeutics, Watertown, MA, USAAff7 0000 0001 0657 5612grid.417886.4Amgen Inc Thousand Oaks California USASTART San Antonio, San Antonio, Texas, USA11 Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USAAff7 0000 0001 0657 5612grid.417886.4Amgen Inc Thousand Oaks California USASTART Midwest, Grand Rapids, Michigan, USA1 Division of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, CanadaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USAChris O`Brien Lifehouse, Camperdown, New South Wales, Australia5 Early Phase Clinical Drug Development in Oncology, START Madrid - CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain6 Prisma Health Institute for Translational Oncology Research, Greenville, South Carolina, USA8 Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University Hospital, Atlanta, Georgia, USA9 GasthuisZusters Antwerpen Sint-Augustinus, Antwerp, Belgium17 Department of Medicine, Weill Cornell Medicine, New York, New York, USA14 Department Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA16 Amgen Inc, South San Francisco, California, USA15 Amgen 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 |
| spellingShingle | Jeanne Tie Dirk Jäger Victor Moreno Dirk Nagorsen Gloria Juan Kyriakos P Papadopoulos Anthony J Olszanski Erik Rasmussen Nehal Lakhani Albiruni RA Razak James M Cleary Michael Boyer Emiliano Calvo Aller William Edenfield R Donald Harvey Annemie Rutten Manish A Shah 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 |
| 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_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_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_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 |
| url | https://jitc.bmj.com/content/8/2/e001006.full |
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