دورية أكاديمية
Tebentafusp in combination with durvalumab and/or tremelimumab in patients with metastatic cutaneous melanoma:A phase 1 study
| العنوان: | Tebentafusp in combination with durvalumab and/or tremelimumab in patients with metastatic cutaneous melanoma:A phase 1 study |
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| المؤلفون: | Hamid, Omid, Hassel, Jessica C., Shoushtari, Alexander N., Meier, Friedegund, Bauer, Todd M., Salama, April K.S., Kirkwood, John M., Ascierto, Paolo A., Lorigan, Paul C., Mauch, Cornelia, Orloff, Marlana, Evans, Thomas R.Jeffry, Holland, Chris, Edukulla, Ramakrishna, Abedin, Shaad E., Middleton, Mark R. |
| المصدر: | Hamid , O , Hassel , J C , Shoushtari , A N , Meier , F , Bauer , T M , Salama , A K S , Kirkwood , J M , Ascierto , P A , Lorigan , P C , Mauch , C , Orloff , M , Evans , T R J , Holland , C , Edukulla , R , Abedin , S E & Middleton , M R 2023 , ' Tebentafusp in combination with durvalumab and/or tremelimumab in patients with metastatic cutaneous melanoma : A phase 1 study ' , Journal .... |
| سنة النشر: | 2023 |
| المجموعة: | The University of Manchester: Research Explorer - Publications |
| مصطلحات موضوعية: | Immune Checkpoint Inhibitors, Immunotherapy, Melanoma, T-Lymphocytes |
| الوصف: | Background Immune checkpoint inhibitors have significantly improved outcomes in first line cutaneous melanoma. However, there is a high unmet need for patients who progress on these therapies and combination therapies are being explored to improve outcomes. Tebentafusp is a first-in-class gp100×CD3 ImmTAC bispecific that demonstrated overall survival (OS) benefit (HR 0.51) in metastatic uveal melanoma despite a modest overall response rate of 9%. This phase 1b trial evaluated the safety and initial efficacy of tebentafusp in combination with durvalumab (anti-programmed death ligand 1 (PDL1)) and/or tremelimumab (anti-cytotoxic T lymphocyte-associated antigen 4) in patients with metastatic cutaneous melanoma (mCM), the majority of whom progressed on prior checkpoint inhibitors. Methods In this open-label, multicenter, phase 1b, dose-escalation trial, HLA-A∗02:01-positive patients with mCM received weekly intravenous tebentafusp with increasing monthly doses of durvalumab and/or tremelimumab starting day 15 of each cycle. The primary objective was to identify the maximum tolerated dose (MTD) or recommended phase 2 dose for each combination. Efficacy analyses were performed in all tebentafusp with durvalumab±tremelimumab treated patients with a sensitivity analysis in those who progressed on prior anti-PD(L)1 therapy. Results 85 patients were assigned to receive tebentafusp in combination with durvalumab (n=43), tremelimumab (n=13), or durvalumab and tremelimumab (n=29). Patients were heavily pretreated with a median of 3 prior lines of therapy, including 76 (89%) who received prior anti-PD(L)1. Maximum target doses of tebentafusp (68 mcg) alone or in combination with durvalumab (20 mg/kg) and tremelimumab (1 mg/kg) were tolerated; MTD was not formally identified for any arm. Adverse event profile was consistent with each individual therapy and there were no new safety signals nor treatment-related deaths. In the efficacy subset (n=72), the response rate was 14%, tumor shrinkage rate was 41% and 1-year OS rate was ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1136/jitc-2023-006747 |
| الإتاحة: | https://doi.org/10.1136/jitc-2023-006747Test https://research.manchester.ac.uk/en/publications/a22c4b91-7500-4140-b016-d3a434e88583Test http://www.scopus.com/inward/record.url?scp=85161095486&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.40F14194 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/jitc-2023-006747 |
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