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A phase I/randomized phase II study of GM.CD40L vaccine in combination with CCL21 in patients with advanced lung adenocarcinoma.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2018 Dec; Vol. 67 (12), pp. 1853-1862. Date of Electronic Publication: 2018 Sep 12. - Publication Year :
- 2018
-
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.
- Subjects :
- Adenocarcinoma immunology
Adult
Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung immunology
Female
Follow-Up Studies
Humans
Lung Neoplasms immunology
Lung Neoplasms therapy
Male
Middle Aged
Prognosis
Survival Rate
Adenocarcinoma therapy
CD40 Ligand administration & dosage
Cancer Vaccines administration & dosage
Carcinoma, Non-Small-Cell Lung therapy
Chemokine CCL21 administration & dosage
Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage
Immunotherapy
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0851
- Volume :
- 67
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 30209589
- Full Text :
- https://doi.org/10.1007/s00262-018-2236-7