Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma
| Autor: | Howard L. Kaufman, Kevin S. Gorski, Mohammed M. Milhem, David R. Minor, Jeffrey Chou, Robert H.I. Andtbacka, Ai Li, Igor Puzanov, Michael Chastain, Omid Hamid, Abraham Antonio Anderson, Lisa Chen |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research medicine.medical_specialty Skin Neoplasms Ipilimumab Gastroenterology 03 medical and health sciences 0302 clinical medicine T-Lymphocyte Subsets Internal medicine Original Reports medicine Clinical endpoint Humans Melanoma Survival analysis Aged Aged 80 and over Oncolytic Virotherapy business.industry Antibodies Monoclonal Middle Aged Stage iiib medicine.disease Tumor Burden Surgery Oncolytic virus Clinical trial Oncolytic Viruses 030104 developmental biology Oncology 030220 oncology & carcinogenesis Female Talimogene laherparepvec business medicine.drug |
| Zdroj: | J Clin Oncol |
| ISSN: | 1527-7755 0732-183X |
| Popis: | Purpose Combining immunotherapeutic agents with different mechanisms of action may enhance efficacy. We describe the safety and efficacy of talimogene laherparepvec (T-VEC; an oncolytic virus) in combination with ipilimumab (a cytotoxic T-lymphocyte–associated antigen 4 checkpoint inhibitor) in patients with advanced melanoma. Methods In this open-label, multicenter, phase Ib trial of T-VEC in combination with ipilimumab, T-VEC was administered intratumorally in week 1 (106 plaque-forming units/mL), then in week 4 and every 2 weeks thereafter (108 plaque-forming units/mL). Ipilimumab (3 mg/kg) was administered intravenously every 3 weeks for four infusions, beginning in week 6. The primary end point was incidence of dose-limiting toxicities. Secondary end points were objective response rate by immune-related response criteria and safety. Results Median duration of treatment with T-VEC was 13.3 weeks (range, 2.0 to 95.4 weeks). Median follow-up time for survival analysis was 20.0 months (1.0 to 25.4 months). Nineteen patients were included in the safety analysis. No dose-limiting toxicities occurred, and no new safety signals were detected. Grade 3/4 treatment-related adverse events (AEs) were seen in 26.3% of patients; 15.8% had AEs attributed to T-VEC, and 21.1% had AEs attributed to ipilimumab. The objective response rate was 50%, and 44% of patients had a durable response lasting ≥ 6 months. Eighteen-month progression-free survival was 50%; 18-month overall survival was 67%. Conclusion T-VEC with ipilimumab had a tolerable safety profile, and the combination appeared to have greater efficacy than either T-VEC or ipilimumab monotherapy. |
| Databáze: | OpenAIRE |
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