1
INVITED SPEAKER PRESENTATION Open Access S49. Clinical activity and development of biomarkers for an engineered anti PDL1 antibody MPDL3280A E Cha From 1st Immunotherapy of Cancer Conference (ITOC1) Munich, Germany. 12-14 March 2014 Background Human cancer cells may suppress the adaptive immune response by expressing PD-L1 and down-regulating T cell activity through PD-L1/PD-1 and PD-L1/B7.1 interactions. Disruption of PD-L1 signaling restores anti- tumor immunity, resulting in durable responses across multiple human tumor types. Here we describe the clini- cal activity and development of predictive biomarkers for MPDL3280A, a human monoclonal antibody with an engineered Fc-domain designed to optimize safety and efficacy, that targets PD-L1 and prevents binding to receptors PD-1 and B7.1. Materials & methods We evaluated a multitude of biomarkers from pretreat- ment tumor specimens collected during clinical study of MPDL3280A. MPDL3280A has been administered as a monotherapy in over 300 pts with locally advanced or metastatic solid tumors in a phase 1 study. Results To date, MPDL3280A has been well tolerated across multiple dose levels and no G3-5 pneumonitis has been reported. Responses were observed in multiple tumor types, including NSCLC, RCC, and melanoma, with ongoing responses seen in the majority of responders. We report the association between pretreatment immune-related markers and response to MPDL3280A. Conclusion Overall, our assessment of tumor specimens not only has resulted in markers that may potentially identify response to MPDL3280A but also has furthered our understanding of the biologic activity of PD-L1 inhibi- tion on treatment. Published: 12 March 2014 doi:10.1186/2051-1426-2-S2-I21 Cite this article as: Cha: S49. Clinical activity and development of biomarkers for an engineered anti PDL1 antibody MPDL3280A. Journal for ImmunoTherapy of Cancer 2014 2(Suppl 2):I21. Submit your next manuscript to BioMed Central and take full advantage of: Convenient online submission Thorough peer review No space constraints or color figure charges Immediate publication on acceptance Inclusion in PubMed, CAS, Scopus and Google Scholar Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Genentech, South San Francisco, CA 94080, USA Cha Journal for ImmunoTherapy of Cancer 2014, 2(Suppl 2):I21 http://www.immunotherapyofcancer.org/content/2/S2/I21 © 2014 Cha; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

S49. Clinical activity and development of biomarkers for an engineered anti PDL1 antibody MPDL3280A

  • Upload
    e

  • View
    216

  • Download
    1

Embed Size (px)

Citation preview

Page 1: S49. Clinical activity and development of biomarkers for an engineered anti PDL1 antibody MPDL3280A

INVITED SPEAKER PRESENTATION Open Access

S49. Clinical activity and development ofbiomarkers for an engineered anti PDL1antibody MPDL3280AE Cha

From 1st Immunotherapy of Cancer Conference (ITOC1)Munich, Germany. 12-14 March 2014

BackgroundHuman cancer cells may suppress the adaptive immuneresponse by expressing PD-L1 and down-regulatingT cell activity through PD-L1/PD-1 and PD-L1/B7.1interactions. Disruption of PD-L1 signaling restores anti-tumor immunity, resulting in durable responses acrossmultiple human tumor types. Here we describe the clini-cal activity and development of predictive biomarkers forMPDL3280A, a human monoclonal antibody with anengineered Fc-domain designed to optimize safety andefficacy, that targets PD-L1 and prevents binding toreceptors PD-1 and B7.1.

Materials & methodsWe evaluated a multitude of biomarkers from pretreat-ment tumor specimens collected during clinical study ofMPDL3280A. MPDL3280A has been administered as amonotherapy in over 300 pts with locally advanced ormetastatic solid tumors in a phase 1 study.

ResultsTo date, MPDL3280A has been well tolerated acrossmultiple dose levels and no G3-5 pneumonitis has beenreported. Responses were observed in multiple tumortypes, including NSCLC, RCC, and melanoma, withongoing responses seen in the majority of responders.We report the association between pretreatmentimmune-related markers and response to MPDL3280A.

ConclusionOverall, our assessment of tumor specimens not onlyhas resulted in markers that may potentially identifyresponse to MPDL3280A but also has furthered our

understanding of the biologic activity of PD-L1 inhibi-tion on treatment.

Published: 12 March 2014

doi:10.1186/2051-1426-2-S2-I21Cite this article as: Cha: S49. Clinical activity and development ofbiomarkers for an engineered anti PDL1 antibody MPDL3280A. Journalfor ImmunoTherapy of Cancer 2014 2(Suppl 2):I21.

Submit your next manuscript to BioMed Centraland take full advantage of:

• Convenient online submission

• Thorough peer review

• No space constraints or color figure charges

• Immediate publication on acceptance

• Inclusion in PubMed, CAS, Scopus and Google Scholar

• Research which is freely available for redistribution

Submit your manuscript at www.biomedcentral.com/submit

Genentech, South San Francisco, CA 94080, USA

Cha Journal for ImmunoTherapy of Cancer 2014, 2(Suppl 2):I21http://www.immunotherapyofcancer.org/content/2/S2/I21

© 2014 Cha; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.