Durvalumab/Tremelimumab in Neoadjuvant and Adjuvant Setting in Patients With HCC Treated by by Percutaneous Ablation Procedure

Summary

This project is a Phase 2 trial testing the safety and efficacy of treatment with Durvalumab/Tremelimumab in neoadjuvant and Durvalumab in adjuvant setting in patients with BCLC A HCC treated by by percutaneous ablation (PA) procedure in a curative intent. DUMELEP is a Multicentre, Phase 2 trial Eligible patients will receive consecutively: 1. 1 Durvalumab 1500 mg/Tremelimumab 300 mg infusion in a neoadjuvant setting 2. percutaneous ablation procedure in a curative attempt at Day 30 3. 11 monthly Durvalumab 1500 mg infusions. 4. Classical follow-up during an additional year (every 3 months)

Timeline

Start

2024-03-28

Primary completion

2027-09-27

Completion

2028-09-27

Publications

• Background Trinchet JC, Bourcier V, Chaffaut C, Ait Ahmed M, Allam S, Marcellin P, Guyader D, Pol S, Larrey D, De Ledinghen V, Ouzan D, Zoulim F, Roulot D, Tran A, Bronowicki JP, Zarski JP, Goria O, Cales P, Peron JM, Alric L, Bourliere M, Mathurin P, Blanc JF, Abergel A, Serfaty L, Mallat A, Grange JD, Buffet C, Bacq Y, Wartelle C, Dao T, Benhamou Y, Pilette C, Silvain C, Christidis C, Capron D, Thiefin G, Hillaire S, Di Martino V, Nahon P, Chevret S; ANRS CO12 CirVir Group. Complications and competing risks of death in compensated viral cirrhosis (ANRS CO12 CirVir prospective cohort). Hepatology. 2015 Sep;62(3):737-50. doi: 10.1002/hep.27743. Epub 2015 Mar 20.
• Background N'Kontchou G, Mahamoudi A, Aout M, Ganne-Carrie N, Grando V, Coderc E, Vicaut E, Trinchet JC, Sellier N, Beaugrand M, Seror O. Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis. Hepatology. 2009 Nov;50(5):1475-83. doi: 10.1002/hep.23181.
• Background Nault JC, Sutter O, Nahon P, Ganne-Carrie N, Seror O. Percutaneous treatment of hepatocellular carcinoma: State of the art and innovations. J Hepatol. 2018 Apr;68(4):783-797. doi: 10.1016/j.jhep.2017.10.004. Epub 2017 Oct 13.
• Background Seror O. Ablative therapies: Advantages and disadvantages of radiofrequency, cryotherapy, microwave and electroporation methods, or how to choose the right method for an individual patient? Diagn Interv Imaging. 2015 Jun;96(6):617-24. doi: 10.1016/j.diii.2015.04.007. Epub 2015 May 14.
• Background Seror O, N'Kontchou G, Ibraheem M, Ajavon Y, Barrucand C, Ganne N, Coderc E, Trinchet JC, Beaugrand M, Sellier N. Large (>or=5.0-cm) HCCs: multipolar RF ablation with three internally cooled bipolar electrodes--initial experience in 26 patients. Radiology. 2008 Jul;248(1):288-96. doi: 10.1148/radiol.2481071101. Epub 2008 May 15.
• Background Sutter O, Calvo J, N'Kontchou G, Nault JC, Ourabia R, Nahon P, Ganne-Carrie N, Bourcier V, Zentar N, Bouhafs F, Sellier N, Diallo A, Seror O. Safety and Efficacy of Irreversible Electroporation for the Treatment of Hepatocellular Carcinoma Not Amenable to Thermal Ablation Techniques: A Retrospective Single-Center Case Series. Radiology. 2017 Sep;284(3):877-886. doi: 10.1148/radiol.2017161413. Epub 2017 Apr 28.
• Background Cheng RG, Bhattacharya R, Yeh MM, Padia SA. Irreversible Electroporation Can Effectively Ablate Hepatocellular Carcinoma to Complete Pathologic Necrosis. J Vasc Interv Radiol. 2015 Aug;26(8):1184-8. doi: 10.1016/j.jvir.2015.05.014. Epub 2015 Jun 26.
• Background Niessen C, Beyer LP, Haimerl M, Schicho A, Stroszczynski C, Wiggermann P, Jung EM. Percutaneous irreversible electroporation of hepatocellular carcinoma: Contrast-enhanced ultrasound-findings during 1-year follow-up. Clin Hemorheol Microcirc. 2019;72(1):85-93. doi: 10.3233/CH-180449.
• Background Niessen C, Beyer LP, Pregler B, Dollinger M, Trabold B, Schlitt HJ, Jung EM, Stroszczynski C, Wiggermann P. Percutaneous Ablation of Hepatic Tumors Using Irreversible Electroporation: A Prospective Safety and Midterm Efficacy Study in 34 Patients. J Vasc Interv Radiol. 2016 Apr;27(4):480-6. doi: 10.1016/j.jvir.2015.12.025. Epub 2016 Feb 26.
• Background Niessen C, Thumann S, Beyer L, Pregler B, Kramer J, Lang S, Teufel A, Jung EM, Stroszczynski C, Wiggermann P. Percutaneous Irreversible Electroporation: Long-term survival analysis of 71 patients with inoperable malignant hepatic tumors. Sci Rep. 2017 Mar 7;7:43687. doi: 10.1038/srep43687.
• Background Bhutiani N, Philips P, Scoggins CR, McMasters KM, Potts MH, Martin RC. Evaluation of tolerability and efficacy of irreversible electroporation (IRE) in treatment of Child-Pugh B (7/8) hepatocellular carcinoma (HCC). HPB (Oxford). 2016 Jul;18(7):593-9. doi: 10.1016/j.hpb.2016.03.609. Epub 2016 May 1.
• Background Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon RT, Han KH, Tak WY, Lee HC, Song T, Roayaie S, Bolondi L, Lee KS, Makuuchi M, Souza F, Berre MA, Meinhardt G, Llovet JM; STORM investigators. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2015 Oct;16(13):1344-54. doi: 10.1016/S1470-2045(15)00198-9. Epub 2015 Sep 8.
• Background El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.
• Background Behm B, Di Fazio P, Michl P, Neureiter D, Kemmerling R, Hahn EG, Strobel D, Gress T, Schuppan D, Wissniowski TT. Additive antitumour response to the rabbit VX2 hepatoma by combined radio frequency ablation and toll like receptor 9 stimulation. Gut. 2016 Jan;65(1):134-43. doi: 10.1136/gutjnl-2014-308286. Epub 2014 Dec 18.
• Background Zerbini A, Pilli M, Laccabue D, Pelosi G, Molinari A, Negri E, Cerioni S, Fagnoni F, Soliani P, Ferrari C, Missale G. Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response. Gastroenterology. 2010 May;138(5):1931-42. doi: 10.1053/j.gastro.2009.12.051. Epub 2010 Jan 11.
• Background Bulvik BE, Rozenblum N, Gourevich S, Ahmed M, Andriyanov AV, Galun E, Goldberg SN. Irreversible Electroporation versus Radiofrequency Ablation: A Comparison of Local and Systemic Effects in a Small-Animal Model. Radiology. 2016 Aug;280(2):413-24. doi: 10.1148/radiol.2015151166. Epub 2016 Jan 27.
• Background Lee JH, Lee JH, Lim YS, Yeon JE, Song TJ, Yu SJ, Gwak GY, Kim KM, Kim YJ, Lee JW, Yoon JH. Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology. 2015 Jun;148(7):1383-91.e6. doi: 10.1053/j.gastro.2015.02.055. Epub 2015 Mar 4.
• Background Iida N, Nakamoto Y, Baba T, Nakagawa H, Mizukoshi E, Naito M, Mukaida N, Kaneko S. Antitumor effect after radiofrequency ablation of murine hepatoma is augmented by an active variant of CC Chemokine ligand 3/macrophage inflammatory protein-1alpha. Cancer Res. 2010 Aug 15;70(16):6556-65. doi: 10.1158/0008-5472.CAN-10-0096. Epub 2010 Jul 27.
• Background Kelley RK, Sangro B, Harris W, Ikeda M, Okusaka T, Kang YK, Qin S, Tai DW, Lim HY, Yau T, Yong WP, Cheng AL, Gasbarrini A, Damian S, Bruix J, Borad M, Bendell J, Kim TY, Standifer N, He P, Makowsky M, Negro A, Kudo M, Abou-Alfa GK. Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. J Clin Oncol. 2021 Sep 20;39(27):2991-3001. doi: 10.1200/JCO.20.03555. Epub 2021 Jul 22.
• Background Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.
• Background Abou-Alfa GK, Lau G, Kudo M, Chan SL, Kelley RK, Furuse J, Sukeepaisarnjaroen W, Kang YK, Van Dao T, De Toni EN, Rimassa L, Breder V, Vasilyev A, Heurgue A, Tam VC, Mody K, Thungappa SC, Ostapenko Y, Yau T, Azevedo S, Varela M, Cheng AL, Qin S, Galle PR, Ali S, Marcovitz M, Makowsky M, He P, Kurland JF, Negro A, Sangro B. Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma. NEJM Evid. 2022 Aug;1(8):EVIDoa2100070. doi: 10.1056/EVIDoa2100070. Epub 2022 Jun 6.

Drugs

Indications