A Phase 1, First-In-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacokinetics of AMG 820 in Adult Subjects With Advanced Solid Tumors

First in human, open-label, sequential dose escalation and expansion study of AMG 820 in subjects with advanced solid tumors.

Start Date31 Mar 2008

Sponsor / Collaborator

AmMax Bio, Inc.Startup

100 Clinical Results associated with AMG-820

100 Translational Medicine associated with AMG-820

100 Patents (Medical) associated with AMG-820

Literatures (Medical) associated with AMG-820

01 Oct 2020·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors

Q2 · MEDICINE

ArticleOA

Author: Rasmussen, Erik ; Smit, Marie-Anne Damiette ; Tie, Jeanne ; Soman, Neelesh ; Lakhani, Nehal ; Razak, Albiruni Ra ; Papadopoulos, Kyriakos P ; Cleary, James M ; Rutten, Annemie ; Shah, Manish A ; Calvo Aller, Emiliano ; Moreno, Victor ; Wong, Hansen ; Nagorsen, Dirk ; Harvey, R Donald ; Edenfield, William ; Olszanski, Anthony J ; Jäger, Dirk ; Juan, Gloria ; Boyer, Michael ; Ryan, David P

BackgroundTo 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 methodsPatients 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.ResultsOverall, 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.ConclusionsThe 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

01 Oct 2017·Clinical Cancer ResearchQ1 · MEDICINE

First-in-Human Study of AMG 820, a Monoclonal Anti-Colony-Stimulating Factor 1 Receptor Antibody, in Patients with Advanced Solid Tumors

Q1 · MEDICINE

Article

Author: Amore, Benny M. ; Nagorsen, Dirk ; Papadopoulos, Kyriakos P. ; Ngarmchamnanrith, Gataree ; Hill, John S. ; Stephenson, Joe ; Tolcher, Anthony W. ; Rasmussen, Erik ; Gluck, Larry ; Martin, Lainie P. ; Olszanski, Anthony J.

AbstractPurpose: Binding of colony-stimulating factor 1 (CSF1) ligand to the CSF1 receptor (CSF1R) regulates survival of tumor-associated macrophages, which generally promote an immunosuppressive tumor microenvironment. AMG 820 is an investigational, fully human CSF1R antibody that inhibits binding of the ligands CSF1 and IL34 and subsequent ligand-mediated receptor activation. This first-in-human phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 820.Experimental Design: Adult patients with relapsed or refractory advanced solid tumors received intravenous AMG 820 0.5 mg/kg once weekly or 1.5 to 20 mg/kg every 2 weeks until disease progression, adverse event (AE), or consent withdrawal.Results: Twenty-five patients received ≥1 dose of AMG 820. AMG 820 was tolerated up to 20 mg/kg; the MTD was not reached. One dose-limiting toxicity was observed (20 mg/kg; nonreversible grade 3 deafness). Most patients (76%) had treatment-related AEs; the most common were periorbital edema (44%), increased aspartate aminotransferase (AST; 28%), fatigue (24%), nausea (16%), increased blood alkaline phosphatase (12%), and blurred vision (12%). No patients had serious or fatal treatment-related AEs; 28% had grade ≥3 treatment-related AEs. Grade 3 AST elevations resolved when treatment was withheld. AMG 820 showed linear pharmacokinetics, with minimal accumulation (<2-fold) after repeated dosing. Pharmacodynamic increases in serum CSF1 concentrations and reduced numbers of skin macrophages were observed. Best response was stable disease in 8 patients (32%).Conclusions: AMG 820 was tolerated with manageable toxicities up to 20 mg/kg every 2 weeks. Pharmacodynamic response was demonstrated, and limited antitumor activity was observed. Clin Cancer Res; 23(19); 5703–10. ©2017 AACR.

100 Deals associated with AMG-820

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 2	BE	AmMax Bio, Inc.Startup	14 Apr 2016
Advanced Malignant Solid Neoplasm	Phase 2	US	AmMax Bio, Inc.Startup	14 Apr 2016
Advanced Malignant Solid Neoplasm	Phase 2	ES	AmMax Bio, Inc.Startup	14 Apr 2016
Advanced Malignant Solid Neoplasm	Phase 2	CA	AmMax Bio, Inc.Startup	14 Apr 2016
Advanced Malignant Solid Neoplasm	Phase 2	AU	AmMax Bio, Inc.Startup	14 Apr 2016
Advanced Malignant Solid Neoplasm	Phase 2	DE	AmMax Bio, Inc.Startup	14 Apr 2016
Non-Small Cell Lung Cancer	Phase 2	AU	AmMax Bio, Inc.Startup	14 Apr 2016
Non-Small Cell Lung Cancer	Phase 2	AU	Amgen, Inc.	14 Apr 2016
Non-Small Cell Lung Cancer	Phase 2	US	AmMax Bio, Inc.Startup	14 Apr 2016
Non-Small Cell Lung Cancer	Discovery	CA	AmMax Bio, Inc.Startup	14 Apr 2016

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02713529 (Pubmed \| J Immunother Cancer) Manual	Phase 1/2	HR-positive/HER2-low Solid Tumors	116	AMG 820+pembrolizumab	(mzzaqgxsut) = fftkdfbbrh umgybkcehe (shviloyrkl ) View more	Negative	01 Oct 2020
AACR2016	Not Applicable	HR-positive/HER2-low Solid Tumors	25	AMG 820	(eflvhapmww) = Most common TRAEs (in > 10% of pts overall) were blurred vision (3, 12%) cbglplwgct (exfsbxamts ) View more	-	15 Jul 2016

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

AMG-820

Overview

Basic Info

Gene Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation