Volume 2 Supplement 3

Abstracts of the 29th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)

Open Access

A Phase Ib/II open-label study to evaluate the safety and efficacy of MEDI-551 in combination with immunomodulating therapy in patients with relapsed or refractory aggressive B cell lymphomas

  • Trishna Goswami1,
  • Paola Canelos1 and
  • Radhika Parikh1
Journal for ImmunoTherapy of Cancer20142(Suppl 3):P73

https://doi.org/10.1186/2051-1426-2-S3-P73

Published: 6 November 2014

Background

MEDI-551, an IgG1k antibody-dependent cellular cytotoxicity (ADCC) enhanced anti-CD19 monoclonal antibody (mAb), has a single-agent response rate of 24% (12% with complete remission [CR]) in heavily pretreated patients with diffuse large B cell lymphoma (DLBCL). MEDI0680 (AMP-514) a humanized IgG4κ mAb against PD-1, blocks inhibitory PD-1 receptors (PD-L1) on T cells to augment immune responses. A combination of MEDI-551/MEDI0680 (AMP-514) may link the intrinsic cytotoxic capability of MEDI-551 with an agent that primes the immune cells required for ADCC or may augment immune responses from tumor cell death by MEDI-551. This study explores this novel combination regimen in patients with multiply relapsed/refractory (R/R) DLBCL who have limited opportunities for cure, and may offer a regimen with less toxicity but equal or better efficacy versus traditional chemotherapy. Study D2852C00004, a Phase Ib/2 dose escalation/expansion study, will determine the maximum tolerated dose (MTD) or the highest protocol-defined dose (HPDD) safety, and activity of the combination of MEDI-551/MEDI0680 (AMP-514) in R/R DLBCL patients who have failed 1-2 prior lines of therapy.

Study objectives

Primary objectives: to determine the MTD or HPDD (in the absence of exceeding the MTD) of MEDI-551/MEDI0680 (AMP-514); dose expansion: to evaluate the safety, tolerability, and clinical activity of MEDI-551/MEDI0680 (AMP-514). Secondary objective: to evaluate the pharmacokinetics and antidrug antibodies of MEDI-551/MEDI0680 (AMP-514) in patients with R/R DLBCL. Exploratory objectives will determine the impact of tumor PD-L1 expression on clinical activity of the combination and will follow soluble PD-1 and PD-L1 expression as biomarkers of activity.

Study design

Standard 3+3 design to determine the MTD of the combination of MEDI-551/MEDI0680 (AMP-514). Patients will receive MEDI-551 12 mg/kg once monthly with 1 of 3 possible doses of MEDI0680 administered bimonthly for 1 year. Thereafter, patients will continue MEDI-551 monthly until progressive disease or toxicity. If a patient experiences progressive disease beyond 12 months of therapy while still receiving MEDI-551 treatment, combination treatment with MEDI0680 (AMP-514) may be resumed for up to 12 additional months. After MTD identification, additional patients will be enrolled in the dose expansion portion to ensure a total sample size of 26 efficacy-evaluable patients. Thirteen of 26 efficacy-evaluable patients receiving the MTD will be required to have PD-L1 expression. Patients will be stratified by refractoriness to chemotherapy, and CD20 therapy and PD-L1 status. Results will inform additional studies to find a chemotherapy-free regimen for frail R/R DLBCL patients.

Authors’ Affiliations

(1)
MedImmune

Copyright

© Goswami et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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