PMID- 33046621
OWN - NLM
STAT- MEDLINE
DCOM- 20211005
LR  - 20211005
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 8
IP  - 2
DP  - 2020 Oct
TI  - Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor 
      antibody, in combination with pembrolizumab in adults with advanced solid tumors.
LID - 10.1136/jitc-2020-001006 [doi]
LID - e001006
AB  - 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 naive 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 naive. 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.
CI  - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Razak, Albiruni Ra
AU  - Razak AR
AD  - Division of Medical Oncology and Hematology, University Health Network, Princess 
      Margaret Cancer Centre, Toronto, Ontario, Canada.
FAU - Cleary, James M
AU  - Cleary JM
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts, USA.
FAU - Moreno, Victor
AU  - Moreno V
AD  - Early Phase Unit START Madrid-FJD, Servicio de Oncologia Medica, Fundacion 
      Jimenez Diaz University Hospital, Madrid, Spain.
FAU - Boyer, Michael
AU  - Boyer M
AD  - Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South 
      Wales, Australia.
FAU - Calvo Aller, Emiliano
AU  - Calvo Aller E
AD  - Early Phase Clinical Drug Development in Oncology, START Madrid - CIOCC, Centro 
      Integral Oncologico Clara Campal, Madrid, Spain.
FAU - Edenfield, William
AU  - Edenfield W
AD  - Prisma Health Institute for Translational Oncology Research, Greenville, South 
      Carolina, USA.
FAU - Tie, Jeanne
AU  - Tie J
AD  - Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, 
      Victoria, Australia.
FAU - Harvey, R Donald
AU  - Harvey RD
AD  - Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory 
      University Hospital, Atlanta, Georgia, USA.
FAU - Rutten, Annemie
AU  - Rutten A
AD  - GasthuisZusters Antwerpen Sint-Augustinus, Antwerp, Belgium.
FAU - Shah, Manish A
AU  - Shah MA
AD  - Department of Medicine, Division of Hematology and Medical Oncology, Solid Tumor 
      Service, Weill Cornell Medicine, New York, New York, USA.
FAU - Olszanski, Anthony J
AU  - Olszanski AJ
AD  - Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, 
      Pennsylvania, USA.
FAU - Jager, Dirk
AU  - Jager D
AD  - Department of Medical Oncology, Nationales Centrum fur Tumorerkrankungen 
      Heidelberg, Heidelberg, Germany.
FAU - Lakhani, Nehal
AU  - Lakhani N
AD  - Developmental Cancer Therapeutics, START Midwest, Grand Rapids, Missouri, USA.
FAU - Ryan, David P
AU  - Ryan DP
AD  - Department Hematology/Oncology, Massachusetts General Hospital, Boston, 
      Massachusetts, USA.
FAU - Rasmussen, Erik
AU  - Rasmussen E
AD  - Amgen Inc, Thousand Oaks, California, USA.
FAU - Juan, Gloria
AU  - Juan G
AD  - Amgen Inc, Thousand Oaks, California, USA.
FAU - Wong, Hansen
AU  - Wong H
AD  - Amgen Inc, South San Francisco, California, USA.
FAU - Soman, Neelesh
AU  - Soman N
AD  - Amgen Inc, Thousand Oaks, California, USA.
FAU - Smit, Marie-Anne Damiette
AU  - Smit MD
AD  - Amgen Inc, Thousand Oaks, California, USA.
FAU - Nagorsen, Dirk
AU  - Nagorsen D
AD  - Amgen Inc, Thousand Oaks, California, USA.
FAU - Papadopoulos, Kyriakos P
AU  - Papadopoulos KP
AUID- ORCID: 0000-0002-0667-2620
AD  - Clinical Research, South Texas Accelerated Research Therapeutics (START), San 
      Antonio, Texas, USA kyri.papadopoulos@startsa.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT02713529
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/pharmacology/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/pharmacology/*therapeutic use
MH  - Antineoplastic Agents, Immunological/pharmacology/*therapeutic use
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
PMC - PMC7552843
OTO - NOTNLM
OT  - clinical trials as topic
OT  - drug therapy, combination
OT  - gastrointestinal neoplasms
OT  - immunotherapy
OT  - lung neoplasms
COIS- Competing interests: ARAR reports research support from Amgen and Merck, during 
      the conduct of the study. JMC reports grants from AstraZeneca, Merck, and Tesaro, 
      outside the submitted work; personal fees from Bristol Myers Squibb, outside the 
      submitted work; and other from Roche, outside the submitted work. VM reports 
      personal fees from Bayer, Bristol Myers Squibb, Janssen, and Pieris, outside the 
      submitted work. MB reports grants from Amgen, during the conduct of the study; 
      grants from Ascentage Pharma, AstraZeneca, Bristol Myers Squibb, Merck Sharp & 
      Dohme, Novartis, Oncomed, and Pfizer, outside the submitted work; personal fees 
      from AstraZeneca, outside the submitted work; and non-financial support from 
      AstraZeneca and Merck Sharp & Dohme, outside the submitted work. ECA reports 
      grants from AbbVie, Amcure, Amgen, AstraZeneca, Bayer, BeiGene, Bristol Myers 
      Squibb, Boehringer Ingelheim, CytomX, Eli Lilly, H3, Incyte, Janssen, Kura, Loxo, 
      Macrogenics, Menarini, Merck Serono, Merck, Merus, Millennium, Nanobiotix, 
      Nektar, Novartis, Pfizer, PharmaMar, Principia, PsiOxus, Puma, Rigontec, 
      Roche/Genentech, Sanofi, START, Taiho, and Tesaro, outside the submitted work; 
      and other from AbbVie, Amcure, AstraZeneca, Celgene, Cerulean Pharma, EUSA, GLG, 
      Guidepoint Global, HM Hospitals Group, International Cancer Consultants, 
      Janssen-Cilag, Nanobiotix, Novartis, NPO Foundation Intheos (Investigational 
      Therapeutics in Oncological Sciences), Oncoart Associated, Pfizer, Pierre Fabre, 
      PsiOxus Therapeutics, Roche/Genentech, Seattle Genetics, Servier, and START, 
      outside the submitted work. WE has nothing to disclose. JT reports other funding 
      from Amgen, during the conduct of the study. RDH reports grants from Amgen and 
      Merck, during the conduct of the study. AR reports honoraria for public speaking 
      and advisory board meetings for Roche, Bristol Myers Squibb, Novartis, Pierre 
      Fabre, and Sanofi. MAS reports grants from Merck, during the conduct of the 
      study. AJO reports personal fees from Merck, during the conduct of the study; and 
      personal fees from Array, Bristol Myers Squibb, Novartis, and Pfizer, outside the 
      submitted work. DJ has nothing to disclose. NL reports other from Amgen, during 
      the conduct of the study; personal fees from Innovent Biologics, outside the 
      submitted work; and other from Alexion, ALX Therapeutics, Apexian, Asana 
      BioSciences, Ascentage, BeiGene, Cerulean Pharma, Constellation, CytomX, 
      Formation Biologics, Forty Seven, Ikena, Incyte, InhibRx, Innovent Biologics, 
      Jounce Therapeutics, Livzon, Loxo, MacroGenics, Merck, Northern Biologics, 
      Odonate Therapeutics, Pfizer, Regeneron, Symphogen, and TaiRx, outside the 
      submitted work. DPR reports equity in Acworth Pharmaceuticals and MPM Capital and 
      is an advisor for 28/7 Therapeutics, Gritstone Oncology, Maverick Therapeutics, 
      MPM Capital, and Oncorus, outside the submitted work. ER is an employee and 
      stockholder of Amgen. GJ is an employee and stockholder of Amgen. HW is an 
      employee and stockholder of Amgen. NS is an employee and stockholder of Amgen. 
      M-ADS is an employee of Amgen. DN is an employee and stockholder of Amgen. KPP 
      reports funding to START for conduct of this clinical trial from Amgen; funding 
      to START for conduct of clinical trials from 3D Medicines, AbbVie, ADC 
      Therapeutics, ArQule, Calithera Biosciences, Curegenix, Daiichi Sankyo, EMD 
      Serono, Formation Biologics, Incyte, Jounce Therapeutics, MabSpace Biosciences, 
      MedImmune, Merck, Mersana, OncoMed, Peloton Therapeutics, Regeneron, Sanofi, and 
      Syros Pharmaceuticals, outside the submitted work; and advisory board fees from 
      ArQule, Basilea, and Bayer, outside the submitted work.
EDAT- 2020/10/14 06:00
MHDA- 2021/10/06 06:00
PMCR- 2020/10/12
CRDT- 2020/10/13 05:33
PHST- 2020/06/30 00:00 [accepted]
PHST- 2020/10/13 05:33 [entrez]
PHST- 2020/10/14 06:00 [pubmed]
PHST- 2021/10/06 06:00 [medline]
PHST- 2020/10/12 00:00 [pmc-release]
AID - jitc-2020-001006 [pii]
AID - 10.1136/jitc-2020-001006 [doi]
PST - ppublish
SO  - J Immunother Cancer. 2020 Oct;8(2):e001006. doi: 10.1136/jitc-2020-001006.