Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311)
BackgroundIntratumoral injection of talimogene laherparepvec evokes a cytotoxic immune response. Therefore, the combination of talimogene laherparepvec with trabectedin and nivolumab may have synergistic effects in advanced sarcomas.Patients and methodsThis phase 2 trial was conducted from May 30, 2...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1116937/full |
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| author | Sant P. Chawla Walter Andree Tellez Hripsime Chomoyan Chrysler Valencia Amir Ahari Nadezhda Omelchenko Stefan Makrievski Don A. Brigham Don A. Brigham Victoria Chua-Alcala Doris Quon Ania Moradkhani Erlinda M. Gordon Erlinda M. Gordon |
| author_facet | Sant P. Chawla Walter Andree Tellez Hripsime Chomoyan Chrysler Valencia Amir Ahari Nadezhda Omelchenko Stefan Makrievski Don A. Brigham Don A. Brigham Victoria Chua-Alcala Doris Quon Ania Moradkhani Erlinda M. Gordon Erlinda M. Gordon |
| author_sort | Sant P. Chawla |
| collection | DOAJ |
| description | BackgroundIntratumoral injection of talimogene laherparepvec evokes a cytotoxic immune response. Therefore, the combination of talimogene laherparepvec with trabectedin and nivolumab may have synergistic effects in advanced sarcomas.Patients and methodsThis phase 2 trial was conducted from May 30, 2019 to January 31, 2022. Endpoints: Primary: Progression free survival rate at month 12. Secondary: Best overall response, progression free survival rate at 6 and 9 months, overall survival rate at 6, 9, and 12 months, incidence of conversion of an unresectable tumor to a resectable tumor, and incidence of adverse events. Eligible patients had to be ≥ 18 years of age, have advanced histologically proven sarcoma, at least 1 previous chemotherapy regimen, and at least one accessible tumor for intratumoral injection. Treatment: Trabectedin intravenously (1.2 mg/m2 q3 weeks), nivolumab intravenously (3 mg/kg q2 weeks), and intratumoral talimogene laherparepvec (1x108 plaque forming units/ml q2 weeks).ResultsMedian time of follow-up: 15.2 months. Efficacy analysis: Thirty-nine patients who had completed at least one treatment cycle and had a follow-up computerized tomography were evaluable for efficacy analysis. Median number of prior therapies: 4 (range 1-11). Progression free survival rate at month 12, 36.7%. Confirmed Best Overall Response by Response Evaluation Criteria in Solid Tumors v1.1 = 3 partial responses, 30 stable disease, 6 progressive disease. Best Overall Response Rate, 7.7%, Disease Control Rate, 84.6%; median progression free survival, 7.8 (95% Confidence Intervals: 4.1-13.1) months; 6-, 9-, 12-month progression free survival rates, 54.5%/45.9%/36.7%; median overall survival 19.3 (95% Confidence Intervals: 12.8 -.) months; 6-, 9- and 12-month overall survival rate, 86.9%/73.3%/73.3%. One patient had a complete surgical resection. Fifty percent of patients had a ≥ grade 3 treatment related adverse events which included anemia (6%), thrombocytopenia (6%), neutropenia (4%), increased alanine transaminase (4%), decreased left ventricular ejection fraction (4%), dehydration (4%), hyponatremia (4%).ConclusionsTaken together these data suggest that the TNT regimen is effective and safe for advanced previously treated sarcomas, and is worth being further studied in a randomized phase 3 trial as first- or second- line treatment for patients with advanced sarcomas. |
| first_indexed | 2024-04-09T13:29:03Z |
| format | Article |
| id | doaj.art-e33f8a62e71649f58f857ead4dd4e0f7 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-09T13:29:03Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e33f8a62e71649f58f857ead4dd4e0f72023-05-10T05:18:23ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.11169371116937Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311)Sant P. Chawla0Walter Andree Tellez1Hripsime Chomoyan2Chrysler Valencia3Amir Ahari4Nadezhda Omelchenko5Stefan Makrievski6Don A. Brigham7Don A. Brigham8Victoria Chua-Alcala9Doris Quon10Ania Moradkhani11Erlinda M. Gordon12Erlinda M. Gordon13Medical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesMedical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesMedical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesMedical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesMedical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesMedical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesMedical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesMedical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesGene and Cell Therapy, Aveni Foundation, Santa Monica, CA, United StatesMedical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesMedical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesMedical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesMedical Oncology, Sarcoma Oncology Research Center, Santa Monica, CA, United StatesGene and Cell Therapy, Aveni Foundation, Santa Monica, CA, United StatesBackgroundIntratumoral injection of talimogene laherparepvec evokes a cytotoxic immune response. Therefore, the combination of talimogene laherparepvec with trabectedin and nivolumab may have synergistic effects in advanced sarcomas.Patients and methodsThis phase 2 trial was conducted from May 30, 2019 to January 31, 2022. Endpoints: Primary: Progression free survival rate at month 12. Secondary: Best overall response, progression free survival rate at 6 and 9 months, overall survival rate at 6, 9, and 12 months, incidence of conversion of an unresectable tumor to a resectable tumor, and incidence of adverse events. Eligible patients had to be ≥ 18 years of age, have advanced histologically proven sarcoma, at least 1 previous chemotherapy regimen, and at least one accessible tumor for intratumoral injection. Treatment: Trabectedin intravenously (1.2 mg/m2 q3 weeks), nivolumab intravenously (3 mg/kg q2 weeks), and intratumoral talimogene laherparepvec (1x108 plaque forming units/ml q2 weeks).ResultsMedian time of follow-up: 15.2 months. Efficacy analysis: Thirty-nine patients who had completed at least one treatment cycle and had a follow-up computerized tomography were evaluable for efficacy analysis. Median number of prior therapies: 4 (range 1-11). Progression free survival rate at month 12, 36.7%. Confirmed Best Overall Response by Response Evaluation Criteria in Solid Tumors v1.1 = 3 partial responses, 30 stable disease, 6 progressive disease. Best Overall Response Rate, 7.7%, Disease Control Rate, 84.6%; median progression free survival, 7.8 (95% Confidence Intervals: 4.1-13.1) months; 6-, 9-, 12-month progression free survival rates, 54.5%/45.9%/36.7%; median overall survival 19.3 (95% Confidence Intervals: 12.8 -.) months; 6-, 9- and 12-month overall survival rate, 86.9%/73.3%/73.3%. One patient had a complete surgical resection. Fifty percent of patients had a ≥ grade 3 treatment related adverse events which included anemia (6%), thrombocytopenia (6%), neutropenia (4%), increased alanine transaminase (4%), decreased left ventricular ejection fraction (4%), dehydration (4%), hyponatremia (4%).ConclusionsTaken together these data suggest that the TNT regimen is effective and safe for advanced previously treated sarcomas, and is worth being further studied in a randomized phase 3 trial as first- or second- line treatment for patients with advanced sarcomas.https://www.frontiersin.org/articles/10.3389/fonc.2023.1116937/fulltalimogene laherparepvecnivolumabtrabectedinsarcomaimmunotherapyalkylating agents |
| spellingShingle | Sant P. Chawla Walter Andree Tellez Hripsime Chomoyan Chrysler Valencia Amir Ahari Nadezhda Omelchenko Stefan Makrievski Don A. Brigham Don A. Brigham Victoria Chua-Alcala Doris Quon Ania Moradkhani Erlinda M. Gordon Erlinda M. Gordon Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311) Frontiers in Oncology talimogene laherparepvec nivolumab trabectedin sarcoma immunotherapy alkylating agents |
| title | Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311) |
| title_full | Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311) |
| title_fullStr | Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311) |
| title_full_unstemmed | Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311) |
| title_short | Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311) |
| title_sort | activity of tnt a phase 2 study using talimogene laherparepvec nivolumab and trabectedin for previously treated patients with advanced sarcomas nct 03886311 |
| topic | talimogene laherparepvec nivolumab trabectedin sarcoma immunotherapy alkylating agents |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1116937/full |
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