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12.09.2018 | Clinical Trial Report Open Access

A phase I/randomized phase II study of GM.CD40L vaccine in combination with CCL21 in patients with advanced lung adenocarcinoma

Zeitschrift:
Cancer Immunology, Immunotherapy
Autoren:
Jhanelle E. Gray, Alberto Chiappori, Charlie C. Williams, Tawee Tanvetyanon, Eric B. Haura, Ben C. Creelan, Jongphil Kim, Theresa A. Boyle, Mary Pinder-Schenck, Farah Khalil, Soner Altiok, Rebecca Devane, David Noyes, Melanie Mediavilla-Varela, Renee Smilee, Emily L. Hopewell, Linda Kelley, Scott J. Antonia
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00262-018-2236-7) contains supplementary material, which is available to authorized users.
Preliminary results were presented as a poster at the American Society of Clinical Oncology (ASCO) (May 31–June 4, 2013; Chicago, Illinois, USA) and as a poster at the 15th Annual World Conference on Lung Cancer (WCLC) (October 27–October 30, 2013; Sydney, Australia).

Abstract

The GM.CD40L vaccine, which recruits and activates dendritic cells, migrates to lymph nodes, activating T cells and leading to systemic tumor cell killing. When combined with the CCL21 chemokine, which recruits T cells and enhances T-cell responses, additive effects have been demonstrated in non-small cell lung cancer mouse models. Here, we compared GM.CD40L versus GM.CD40L plus CCL21 (GM.CD40L.CCL21) in lung adenocarcinoma patients with ≥ 1 line of treatment. In this phase I/II randomized trial (NCT01433172), patients received intradermal vaccines every 14 days (3 doses) and then monthly (3 doses). A two-stage minimax design was used. During phase I, no dose-limiting toxicities were shown in three patients who received GM.CD40L.CCL21. During phase II, of evaluable patients, 5/33 patients (15.2%) randomized for GM.DCD40L (p = .023) and 3/32 patients (9.4%) randomized for GM.DCD40L.CCL21 (p = .20) showed 6-month progression-free survival. Median overall survival was 9.3 versus 9.5 months with GM.DCD40L versus GM.DCD40L.CCL21 (95% CI 0.70–2.25; p = .44). For GM.CD40L versus GM.CD40L.CCL21, the most common treatment-related adverse events (TRAEs) were grade 1/2 injection site reaction (51.4% versus 61.1%) and grade 1/2 fatigue (35.1% versus 47.2%). Grade 1 immune-mediated TRAEs were isolated to skin. No patients showed evidence of pseudo-progression or immune-related TRAEs of grade 1 or greater of pneumonitis, endocrinopathy, or colitis, and none discontinued treatment due to toxicity. Although we found no significant associations between vaccine immunogenicity and outcomes, in limited biopsies, one patient treated with GMCD40L.CCL21 displayed abundant tumor-infiltrating lymphocytes. This possible effectiveness warrants further investigation of GM.CD40L in combination approaches.

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Zusatzmaterial
Supplementary material 1 (PDF 233 KB)
262_2018_2236_MOESM1_ESM.pdf
Literatur
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