Immunogenicity of pembrolizumab in patients with advanced tumors.

Immunogenicity of pembrolizumab in patients with advanced tumors.

Publication date: Aug 08, 2019

Pembrolizumab is a potent, humanized, monoclonal anti-programmed death 1 antibody that has demonstrated effective antitumor activity and acceptable safety in multiple tumor types. Therapeutic biologics can result in the development of antidrug antibodies (ADAs), which may alter drug clearance and neutralize target binding, potentially reducing drug efficacy; such immunogenicity may also result in infusion reactions, anaphylaxis, and immune complex disorders. Pembrolizumab immunogenicity and its impact on exposure, safety, and efficacy was assessed in this study.

Pembrolizumab immunogenicity was assessed in 3655 patients with advanced or metastatic cancer treated in 12 clinical studies. Patients with melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, colorectal cancer, urothelial cancer, and Hodgkin lymphoma were treated with pembrolizumab at 2 mg/kg every 3 weeks, 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 200 mg every 3 weeks. An additional study involving 496 patients with stage III melanoma treated with 200 mg adjuvant pembrolizumab every 3 weeks after complete resection was analyzed separately.

Of 3655 patients, 2000 were evaluable for immunogenicity analysis, 36 (1.8%) were treatment-emergent (TE) ADA-positive; 9 (0.5%) of these TE-positive patients had antibodies with neutralizing capacity. The presence of pembrolizumab-specific ADAs did not impact pembrolizumab exposure, nor did pembrolizumab immunogenicity affect the incidence of drug-related adverse events (AEs) or infusion-related reactions. There was no clear relationship between the presence of pembrolizumab-specific ADAs and changes in tumor size across treatment regimens. Of the 496 patients treated with pembrolizumab as adjuvant therapy, 495 were evaluable, 17 (3.4%) were TE ADA-positive; none had neutralizing antibodies.

The incidence of TE (neutralizing positive) ADAs against pembrolizumab was low in patients with advanced tumors. Furthermore, immunogenicity did not appear to have any clinically relevant effects on the exposure, safety, or efficacy of pembrolizumab., NCT01295827 (February 15, 2011), NCT01704287 (October 11, 2012), NCT01866319 (May 31, 2013), NCT01905657 (July 23, 2013), NCT02142738 (May 20, 2014), NCT01848834 (May 8, 2013), NCT02255097 (October 2, 2014), NCT02460198 (June 2, 2015), NCT01953692 (October 1, 2013), NCT02453594 (May 25, 2015), NCT02256436 (October 3, 2014), NCT02335424 (January 9, 2015), NCT02362594 (February 13, 2015).

van Vugt, M.J.H., Stone, J.A., De Greef, R.H.J.M.M., Snyder, E.S., Lipka, L., Turner, D.C., Chain, A., Lala, M., Li, M., Robey, S.H., Kondic, A.G., De Alwis, D., Mayawala, K., Jain, L., and Freshwater, T. Immunogenicity of pembrolizumab in patients with advanced tumors. 23703. 2019 J Immunother Cancer (7):1.

Concepts Keywords
ADA III melanoma
ADAs Adjuvant therapy
Adjuvant Medicine
Adjuvant Therapy Clinical medicine
Anaphylaxis Medical specialties
Antibodies Immunology
Antibody Breakthrough therapy
Biologics Antineoplastic drugs
Colorectal Cancer Immune system
Immune Complex Merck
Immunogenicity Pembrolizumab
Incidence Immunogenicity
Infusion Monoclonal antibody
Lung Cancer Antibodies
Squamous Carcinoma
Urothelial Cancer


Type Source Name
disease DOID ADA
disease DOID Hodgkin lymphoma
disease MESH Hodgkin lymphoma
pathway BSID Colorectal cancer
disease DOID colorectal cancer
disease MESH colorectal cancer
disease DOID head and neck squamous cell carcinoma
disease MESH head and neck squamous cell carcinoma
pathway BSID Non-small cell lung cancer
disease DOID non-small cell lung cancer
disease MESH non-small cell lung cancer
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
disease DOID cancer
disease MESH anaphylaxis
disease MESH development
disease MESH death
disease MESH tumors
drug DRUGBANK Pembrolizumab


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