A shared tumor-antigen RNA-lipoplex vaccine with/without anti-PD1 in patients with checkpoint-inhibition experienced melanoma
| العنوان: | A shared tumor-antigen RNA-lipoplex vaccine with/without anti-PD1 in patients with checkpoint-inhibition experienced melanoma |
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| المؤلفون: | Jochen Utikal, Sebastian Attig, Maike Gold, Melanie Leierer, Andreas Pinter, Julian Sikorski, Katarina Cuk, Evelyna Derhovanessian, Matthias Miederer, Ö. Türeci, Carmen Loquai, Heidrun Mitzel-Rink, Robert A. Jabulowsky, Ugur Sahin, Roland Kaufmann, Petra Oehm, Jessica C. Hassel, Doreen Schwarck-Kokarakis, Isabel Vogler, Stephan Grabbe |
| المصدر: | Journal of Clinical Oncology. 38:3136-3136 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cancer Research, business.industry, Melanoma, Immune checkpoint inhibitors, Cancer, RNA, medicine.disease, Tumor antigen, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Cancer research, Medicine, In patient, business, Anti pd1, 030215 immunology, Lipoplex |
| الوصف: | 3136 Background: Cancer vaccines are considered unsuitable for patients with advanced tumours and have not been clinically successful. Methods: Lipo-MERIT is an ongoing phase 1/2 trial (NCT02410733) with melanoma FixVac, a liposomal RNA vaccine targeting four non-mutant shared tumour-associated antigens (TAAs) (MAGE-A3, NY-ESO-1, tyrosinase, TPTE). Patients with stage IIIB-C and IV melanoma are eligible. The trial comprises 7 dose escalation and 3 dose expansion cohorts, the latter with FixVac alone or combined with anti-PD1. Eight doses of FixVac are administered i.v. weekly/bi-weekly followed by optional continued monthly treatment. This abstract summarizes the findings of an exploratory interim analysis (cut-off JUL2019) of 89 patients. Results: 42 of 89 patients had measurable disease at baseline and were eligible for assessment of best objective overall response. All but one patient were stage IV and had undergone previous lines of treatment, 41 patients were checkpoint-inhibitor (CPI)-experienced, and 35 had been exposed to both anti-CTLA4 and anti-PD1 therapy. In the vaccine monotherapy group (n = 25) three patients experienced a partial response (PR) and 7 patients had stable disease (SD). An additional patient showed a complete metabolic remission of metastatic lesions based on [18F]-FDG PET/CT imaging. In the group of patients treated with melanoma FixVac and PD1 blockade, 6 of 17 patients developed a PR. Patients with PR showed induction of poly-epitopic and strong CD4+ and CD8+ T cell immunity against the vaccine antigens. The number of antigen-specific cytotoxic T cells in some responders reached up to low 2-digit percentages of circulating CD8+ T cells and was maintained at high levels by continued vaccination. Overall, 75% of the 50 patients tested by ex vivo IFNg ELISpot analysis and all 20 patients tested by IFNg ELISpot after in vitro stimulation showed vaccine-induced immune responses against at least one vaccine antigen. Typically, antigen-specific T cells ramped up within the first 4-8 weeks to single-digit and low double-digit percent fractions of circulating CD8+ T cells. Immune responses were of effector memory phenotype and their strength and frequency did not depend on disease status at baseline (measurable versus non-measurable disease), on vaccine dose or on treatment (FixVac alone versus in combination with anti-PD1). Conclusions: FixVac alone and in combination with anti-PD1 mediates durable objective responses in pre-treated, CPI experienced patients with advanced progressing melanoma. Clinical trial information: NCT02410733 . |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::c5690a55b4aa00d44cf018af9bce6c5aTest https://doi.org/10.1200/jco.2020.38.15_suppl.3136Test |
| رقم الانضمام: | edsair.doi...........c5690a55b4aa00d44cf018af9bce6c5a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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