Intratumoral talimogene laherparepvec injection with concurrent preoperative radiation in patients with locally advanced soft-tissue sarcoma of the trunk and extremities: phase IB/II trial
Autor: | Kokou D. Zamba, Maheen Rajput, David P. Kuehn, Jon Houtman, Chinemerem Abanonu, Steven Varga, Laura Stephens, Varun Monga, Sarah L. Mott, Weizhou Zhang, Lei Wang, Munir R. Tanas, Omar Jaber, Sudershan K. Bhatia, Catherine M. Metz, Sarag Boukhar, Bryan G. Allen, Jon Thomason, Benjamin J. Miller, Carryn M. Anderson, Stacey Hartwig, Mohammed M. Milhem |
---|---|
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male Cancer Research medicine.medical_treatment Herpesvirus 1 Human 0302 clinical medicine Antineoplastic Agents Immunological Immunology and Allergy Medicine RC254-282 Tumor Biomarkers Aged 80 and over Oncolytic Virotherapy medicine.diagnostic_test Soft tissue sarcoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Sarcoma Middle Aged Oncology 030220 oncology & carcinogenesis Preoperative Period Molecular Medicine Female Radiology Talimogene laherparepvec Adult medicine.medical_specialty Immunology 03 medical and health sciences Biopsy Humans Clinical Trials Aged Pharmacology Myxoid liposarcoma Biological Products Radiotherapy business.industry Phase II as Topic Extremities medicine.disease Oncolytic virus Clinical trial Radiation therapy Oncolytic and Local Immunotherapy 030104 developmental biology business |
Zdroj: | Journal for Immunotherapy of Cancer Journal for ImmunoTherapy of Cancer, Vol 9, Iss 7 (2021) |
ISSN: | 2051-1426 |
Popis: | BackgroundSoft-tissue sarcomas (STS) in the extremities and trunk treated with standard-of-care preoperative external beam radiation therapy (EBRT) followed by surgical resection are associated with local and distant relapses. In preclinical studies, oncolytic virotherapy in sarcoma has demonstrated antitumor effects via direct intratumoral oncolysis and cytotoxic T-cell–mediated immune responses. Talimogene laherparepvec (TVEC) is a replication-competent, immune-enhanced, oncolytic herpes simplex virus type 1 engineered for intratumoral injection; it has been approved by the FDA for the treatment of locally advanced and metastatic melanoma.MethodsWe explored a novel combination of TVEC with standard-of-care EBRT administered preoperatively in patients with locally advanced STS of the extremities and trunk in a phase IB/II clinical trial. Thirty patients with primary STS >5 cm for which EBRT was indicated to achieve negative margins were enrolled. FDA-approved TVEC doses were used. Immune correlative studies in peripheral blood, biopsy and resected tumor tissues were performed.ResultsNo dose-limiting toxicity was observed. Adverse events were similar to those reported in prior studies with TVEC. One patient with myxoid liposarcoma exhibited a partial response. Seven of the 29 (24%) evaluable patients achieved 95% pathological necrosis. None of the patients developed a herpes infection due to the treatment. Eight of the 29 (27%) patients developed postoperative wound complications, which is consistent with previous studies. None of the patients developed local recurrence after surgical resection of the primary sarcoma. 2-year progression-free and overall survival were 57% and 88%, respectively. Caspase-3 demonstrated increased expression of both in TVEC-treated tissue samples as compared with control samples treated with radiation alone.ConclusionPreoperative intratumoral TVEC with concurrent EBRT for locally advanced STS is safe and well-tolerated. This combination treatment may enhance immune responses in some cases but did not increase the proposed rate of pathological necrosis. The Caspase-3 biomarker may be associated with a positive effect of TVEC in sarcoma tumor tissue and should be explored in future studies.Trial registration numberNCT02453191. |
Databáze: | OpenAIRE |
Externí odkaz: |