A phase II trial of durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial carcinoma and endometrial carcinosarcoma
| العنوان: | A phase II trial of durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial carcinoma and endometrial carcinosarcoma |
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| المؤلفون: | Jason A. Konner, Rachel N. Grisham, Tiffany A. Troso-Sandoval, Stuart M. Lichtman, Krysten Soldan, Dmitriy Zamarin, Vicky Makker, Louise Ligresti, Chrisann Kyi, Sarah J. Schweber, Alexia Iasonos, William P. Tew, Maria M. Rubinstein, Roisin E. O'Cearbhaill, Carol Aghajanian, Imogen Caird, Karen Cadoo, Claire F. Friedman, Jasmeet Chadha Singh, Qin Zhou |
| المصدر: | Journal of Clinical Oncology. 37:5582-5582 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Cancer Research, Durvalumab, medicine.drug_class, business.industry, Endometrial carcinosarcoma, Monoclonal antibody, medicine.disease, Programmed cell death ligand 1, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, medicine, Cancer research, Carcinoma, Cytotoxic T cell, In patient, business, Tremelimumab, 030215 immunology, medicine.drug |
| الوصف: | 5582 Background: Monoclonal antibodies Durvalumab (D) and Tremelimumab (T) inhibit binding of programmed cell death ligand 1 (PDL1) to PD1 and inhibit activation of cytotoxic T-lymphocyte-associated protein 4 (CTLA4), respectively, resulting in improved tumor immunosurveillance. There is rationale to study D and DT based on recent genomic and tumor microenvironment evaluation of endometrial cancer (EC). Methods: Eligible patients (pts) were randomized to D or DT. Pts received D 1500 mg intravenously (IV) every 4 weeks (wks). DT therapy pts received D 1500 mg IV every 4 wks and T 75 mg IV every 4 wks for 4 cycles, followed by D 1500 mg IV every 4 wks until progression or unacceptable toxicities. Pts were stratified by histology with 10 carcinosarcoma or MSI-H EC pts per arm. Efficacy assessments were every 8 wks and treatment related adverse events (TRAEs) were assessed per CTCAE v.4.03. The primary endpoint was overall response rate (ORR) by RECIST v1.1. Descriptive statistics and 90% one sided CI are reported. Progression free survival (PFS) rate at 24 wks (PFS24wks) was estimated by Kaplan Meier method. Results: At planned interim analysis, 56 pts were enrolled (28 per arm). 15 pts: carcinosarcoma, 15 pts: endometrioid (3: Gr1), 14 pts: serous, and 12 pts: other histology. 5(9%) pts: MSI-H, 48(86%) pts: microsatellite stable (MSS), 3(5%): unknown. 2 pts were excluded due to early death. 27 pts per arm were evaluable for efficacy. In the D arm: 1 pt had complete response (CR)(MSS) and 3 pts had a partial response (PR) (2:MSS, 1:MSI-H) with an ORR of 14.8% (CI: 6.6-100%). The median PFS was 7.6 wks and PFS24wks was 13.3% (CI 6.1-100%). Median duration of response (DOR) was 16 wks in the D arm. In the DT arm, 2 pts achieved CR (1:MSI-H, 1:MSS) and 1 had PR (MSS). The ORR was 11.1% (CI: 4.2-100%). Median PFS was 8.1 wks, PFS24wks was 18.5% (CI 10.1-100%) and DOR was 8 wks. Grade 3 TRAEs occurred in 2 (7%) pts in D and 9 (32%) pts in DT. Grade 4 TRAEs occurred 1 (4%) pt in D and 3 (11%) pts in DT. 2 pts discontinued due to a TRAE. Most common TRAEs in total were fatigue (23%), diarrhea (20%), nausea (14%), vomiting (13%) and pruritis (11%). Conclusions: D and DT show modest activity in EC. No new safety signals were identified. Second stage accrual is ongoing. Clinical trial information: NCT03015129. |
| تدمد: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2019.37.15_suppl.5582 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::11222bf467fa49ecb33ca2eda2913303 https://doi.org/10.1200/jco.2019.37.15_suppl.5582 |
| رقم الانضمام: | edsair.doi...........11222bf467fa49ecb33ca2eda2913303 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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| DOI: | 10.1200/jco.2019.37.15_suppl.5582 |