Academic Journal
Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results
| العنوان: | Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results |
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| المؤلفون: | Hassan, Raffit, Butler, Marcus, O’Cearbhaill, Roisin E., Oh, David Y., Johnson, Melissa, Zikaras, Kevin, Smalley, Munisha, Ross, Michael, Tanyi, Janos L., Ghafoor, Azam, Shah, Nirali N., Saboury, Babak, Cao, Liang, Quintás-Cardama, Alfonso, Hong, David |
| المصدر: | Nature Medicine ; volume 29, issue 8, page 2099-2109 ; ISSN 1078-8956 1546-170X |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | The T cell receptor fusion construct (TRuC) gavocabtagene autoleucel (gavo-cel) consists of single-domain anti-mesothelin antibody that integrates into the endogenous T cell receptor (TCR) and engages the signaling capacity of the entire TCR upon mesothelin binding. Here we describe phase 1 results from an ongoing phase1/2 trial of gavo-cel in patients with treatment-refractory mesothelin-expressing solid tumors. The primary objectives were to evaluate safety and determine the recommended phase 2 dose (RP2D). Secondary objectives included efficacy. Thirty-two patients received gavo-cel at increasing doses either as a single agent ( n = 3) or after lymphodepletion (LD, n = 29). Dose-limiting toxicities of grade 3 pneumonitis and grade 5 bronchioalveolar hemorrhage were noted. The RP2D was determined as 1 × 10 8 cells per m 2 after LD. Grade 3 or higher pneumonitis was seen in 16% of all patients and in none at the RP2D; grade 3 or higher cytokine release syndrome occurred in 25% of all patients and in 15% at the RP2D. In 30 evaluable patients, the overall response rate and disease control rate were 20% (13% confirmed) and 77%, respectively, and the 6-month overall survival rate was 70%. Gavo-cel warrants further study in patients with mesothelin-expressing cancers given its encouraging anti-tumor activity, but it may have a narrow therapeutic window. ClinicalTrials.gov identifier: NCT03907852 . |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41591-023-02452-y |
| الاتاحة: | http://dx.doi.org/10.1038/s41591-023-02452-y https://www.nature.com/articles/s41591-023-02452-y.pdf https://www.nature.com/articles/s41591-023-02452-y |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.421408B1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41591-023-02452-y |
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