A phase I/randomized phase II study of GM.CD40L vaccine in combination with CCL21 in patients with advanced lung adenocarcinoma
| العنوان: | A phase I/randomized phase II study of GM.CD40L vaccine in combination with CCL21 in patients with advanced lung adenocarcinoma |
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| المؤلفون: | Tawee Tanvetyanon, Melanie Mediavilla-Varela, Renee Smilee, David Noyes, Rebecca Devane, Scott J. Antonia, Mary Pinder-Schenck, Emily L. Hopewell, Theresa A. Boyle, Charles Williams, Jhanelle E. Gray, Alberto Chiappori, Ben C. Creelan, Soner Altiok, Jongphil Kim, Linda Kelley, Farah Khalil, Eric B. Haura |
| المصدر: | Cancer Immunology, Immunotherapy |
| بيانات النشر: | Springer Berlin Heidelberg, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cancer Research, Lung Neoplasms, medicine.medical_treatment, Phases of clinical research, Gastroenterology, law.invention, 0302 clinical medicine, Randomized controlled trial, Non-small cell lung cancer, law, Carcinoma, Non-Small-Cell Lung, Cancer vaccine, Immunology and Allergy, Aged, 80 and over, biology, Middle Aged, Prognosis, 3. Good health, Survival Rate, Oncology, Chemokine, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, Immunotherapy, Adult, medicine.medical_specialty, Immunology, CD40 Ligand, Cancer Vaccines, 03 medical and health sciences, Internal medicine, Injection site reaction, medicine, Humans, Adverse effect, Pneumonitis, Aged, CD40, Chemokine CCL21, business.industry, Granulocyte-Macrophage Colony-Stimulating Factor, medicine.disease, 030104 developmental biology, Clinical Trial Report, biology.protein, business, Follow-Up Studies |
| الوصف: | 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. Electronic supplementary material The online version of this article (10.1007/s00262-018-2236-7) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1432-0851 0340-7004 0143-3172 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3228408ae38b46cf9b37b8e1b51a8ecaTest http://europepmc.org/articles/PMC6244998Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3228408ae38b46cf9b37b8e1b51a8eca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320851 03407004 01433172 |
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