Phase IIIb safety results from an expanded-access protocol of talimogene laherparepvec for patients with unresected, stage IIIB-IVM1c melanoma

被引:32
作者
Chesney, Jason [1 ]
Awasthi, Sanjay [2 ]
Curti, Brendan [4 ]
Hutchins, Laura [5 ]
Linette, Gerald [6 ]
Triozzi, Pierre [7 ]
Tan, Marcus C. B. [9 ]
Brown, Russell E. [10 ]
Nemunaitis, John [11 ]
Whitman, Eric [12 ]
Windham, Christopher [8 ]
Lutzky, Jose [13 ]
Downey, Gerald F. [15 ]
Batty, Nicolas [3 ]
Amatruda, Thomas [14 ]
机构
[1] Univ Louisville, Dept Med, Louisville, KY 40292 USA
[2] City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA USA
[3] Amgen Inc, Dept Clin Res, Thousand Oaks, CA 91320 USA
[4] Providence Canc Ctr, Earle A Chiles Res Inst, Portland, OR USA
[5] Univ Arkansas Med Sci, Dept Internal Med, Div Hematol Oncol, Little Rock, AR 72205 USA
[6] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA
[7] Wake Forest Sch Med, Sect Hematol & Oncol, Winston Salem, NC USA
[8] Cone Hlth, Dept Oncol, Greensboro, NC USA
[9] Univ S Alabama, Div Surg Oncol, Mobile, AL 36688 USA
[10] Ochsner Med Ctr, Dept Surg, New Orleans, LA USA
[11] Mary Crowley Canc Res Ctr, Dept Med Hematol & Oncol, Dallas, TX USA
[12] Atlantic Hlth Syst Canc Care, Atlantic Melanoma Ctr, Dept Endocrine & Oncol Surg, Morristown, NJ USA
[13] Mt Sinai Med Ctr, Div Hematol & Oncol, Miami Beach, FL 33140 USA
[14] Minnesota Oncol, Dept Hematol & Oncol, Fridley, MN USA
[15] Amgen Ltd, Ctr Design & Anal, Cambridge, England
关键词
cancer immunotherapy; cutaneous melanoma; expanded access; oncolytic virus; talimogene laherparepvec; METASTATIC MELANOMA; CANCER; IPILIMUMAB; NIVOLUMAB; THERAPY;
D O I
10.1097/CMR.0000000000000399
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Talimogene laherparepvec is a genetically modified herpes simplex virus-1-based oncolytic immunotherapy for the local treatment of unresectable cutaneous, subcutaneous, and nodal tumors in patients with melanoma recurrence following surgery. We aim to describe the safety of talimogene laherparepvec. Intralesional talimogene laherparepvec was administered at less than or equal to 4mlx106 PFU/ml at protocol day 1, then less than or equal to 4mlx108 PFU/ml 21 days later, and then every 14 days. Treatment continued until complete response, absence of injectable tumors, progressive disease, intolerance, or US Food and Drug Administration approval. Adverse events were graded during and 30 days after the end of treatment. Lesions suspected to have herpetic origin were tested for talimogene laherparepvec DNA by quantitative PCR (qPCR). Between September 2014 and October 2015, 41 patients were enrolled with stage IIIB (22%), IIIC (37%), IVM1a (34%), IVM1b (5%), and IVM1c (2%) melanoma. The median age was 72 (range: 32-96) years and 54% of the patients were men. Patients had an ECOG performance status of 0 (68%) or 1 (32%). The median treatment duration was 13.1 (3.0-41.1) weeks. Treatment-related adverse events of greater than or equal to grade 3 were reported in three (7.3%) patients and included vomiting, upper abdominal pain, chills, hyperhidrosis, nausea, pyrexia, and wound infection. Suspected herpetic lesions were swabbed in five (12%) patients. One of the five tested positive for talimogene laherparepvec DNA by qPCR, but this lesion had been injected previously with talimogene laherparepvec. During the study, five patients completed treatment because of complete response per investigators. In the clinical practice setting, talimogene laherparepvec has a safety profile comparable to that observed in previous clinical trials. Talimogene laherparepvec (IMLYGIC) is now approved in the US, European Union, and Australia. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
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收藏
页码:44 / 51
页数:8
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