Abstract A76: Enhancement of cetuximab-induced antibody-dependent cellular cytotoxicity with lenalidomide in advanced solid tumors: A Phase I trial.
Molecular Cancer Therapeutics(2013)
Abstract
Introduction: Antibody-dependent cellular cytotoxicity (ADCC) is one mechanism of action of monoclonal antibody (mAb) therapy. ADCC occurs via the innate immune system9s ability to recognize mAb coated cancer cells and activate effector cells. Lenalidomide is an immunomodulatory agent with capacity to stimulate T cell proliferation, activate natural killer cells, and effect immune cytokines including IL-2, IL-12, and interferon gamma. Both preclinical and clinical data demonstrate the ability of lenalidomide to increase ADCC activity of mAb therapy. This Phase I CTEP sponsored trial aims to evaluate the combination of cetuximab with lenalidomide to enhance ADCC activity in advanced colorectal (CRC) and head and neck squamous cell cancers (HNSCC). Patients/Methods: This Phase I dose escalation trial included patients with locally advanced or metastatic CRC (KRAS wild type) or HNSCC. Treatment consisted of cetuximab 500 mg/m2 IV every 2 weeks with lenalidomide orally days 1-21 every 28 days. Cetuximab dose was the same in all cohorts although dose reductions were permitted for toxicity. Three dose levels of lenalidomide were evaluated (15 mg, 20 mg, and 25 mg). Prior treatment with cetuximab, panitumumab, or other EGFR directed therapy was allowed. Planned correlative studies include measurement of ADCC using an in vitro chromium release assay, serum interferon gamma and NK cytokine profiles, and Fc gamma receptor polymorphisms. Results: A total of 22 patients have been treated (19 CRC, 3 HNSCC). Grade 3 fatigue has been the only observed dose-limiting toxicity. One partial response was observed and 7 patients had stable disease as best response. Two patients remain on treatment. The recommended Phase II dose is cetuximab 500 mg/m2 with lenalidomide 25 mg daily days 1-21. Conclusions: Cetuximab and lenalidomide was well-tolerated with minimal activity. Although response was not a primary endpoint, there is evidence of anti-tumor activity and clinical efficacy. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A76. Citation Format: Erin M. Bertino, Jeffrey S. Rose, Christina Wu, Tanios Bekaii-Saab, Panayiotis S. Savvides, Richard M. Goldberg, Miguel Villalona, Gerard Lozanski, William Carson, Michael Grever, Gregory Otterson. Enhancement of cetuximab-induced antibody-dependent cellular cytotoxicity with lenalidomide in advanced solid tumors: A Phase I trial. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A76.
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Key words
cytotoxicity,lenalidomide,advanced solid tumors,cetuximab-induced,antibody-dependent
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