A Study of the Safety and Antitumoral Efficacy of Nivolumab After SIRT for the Treatment of Patients With HCC

Summary

The purpose of this study is to evaluate the effect of the anti-programmed death 1 (PD-1) agent nivolumab following selective internal radiation therapy (SIRT) for patients with unresectable hepatocellular carcinoma (HCC). SIRT using yttrium90-loaded microspheres is increasingly used to treat patients with HCC, particularly those that are not good candidates for transarterial chemoembolization or TACE. SIRT induces disease control (objective tumor remission or stabilization) in most patients while progression usually results from the growth of new lesions. SIR-Spheres are resin-made microspheres used for SIRT. On the other hand, nivolumab is under clinical development for the treatment of more advanced HCC. Available data in patients that mostly had progression to other therapies and vascular involvement or metastatic disease show significant systemic antitumor activity that results in durable objective remissions and disease stabilizations. Therefore, in patients with HCC that has not spread beyond the liver, the systemic action of nivolumab may improve the anti-tumor effect of SIRT. Furthermore, by inducing immunogenic tumor cell death, SIRT may have a synergistic effect with nivolumab.

Timeline

Start

2017-09-11

Primary completion

2020-03-01

Completion

2020-11-04

Publications

• Background Sangro B, Salem R. Transarterial chemoembolization and radioembolization. Semin Liver Dis. 2014 Nov;34(4):435-43. doi: 10.1055/s-0034-1394142. Epub 2014 Nov 4.
• Background Bolondi L, Burroughs A, Dufour JF, Galle PR, Mazzaferro V, Piscaglia F, Raoul JL, Sangro B. Heterogeneity of patients with intermediate (BCLC B) Hepatocellular Carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2012 Nov;32(4):348-59. doi: 10.1055/s-0032-1329906. Epub 2013 Feb 8.
• Background Sangro B, Carpanese L, Cianni R, Golfieri R, Gasparini D, Ezziddin S, Paprottka PM, Fiore F, Van Buskirk M, Bilbao JI, Ettorre GM, Salvatori R, Giampalma E, Geatti O, Wilhelm K, Hoffmann RT, Izzo F, Inarrairaegui M, Maini CL, Urigo C, Cappelli A, Vit A, Ahmadzadehfar H, Jakobs TF, Lastoria S; European Network on Radioembolization with Yttrium-90 Resin Microspheres (ENRY). Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology. 2011 Sep 2;54(3):868-78. doi: 10.1002/hep.24451. Epub 2011 Jun 30.
• Background Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
• Background Gil-Alzugaray B, Chopitea A, Inarrairaegui M, Bilbao JI, Rodriguez-Fraile M, Rodriguez J, Benito A, Dominguez I, D'Avola D, Herrero JI, Quiroga J, Prieto J, Sangro B. Prognostic factors and prevention of radioembolization-induced liver disease. Hepatology. 2013 Mar;57(3):1078-87. doi: 10.1002/hep.26191. Epub 2013 Feb 15.
• 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.
• De la Torre-Alaez M, Matilla A, Varela M, Inarrairaegui M, Reig M, Lledo JL, Arenas JI, Lorente S, Testillano M, Marquez L, Iserte G, Argemi J, Gomez-Martin C, Rodriguez-Fraile M, Bilbao JI, Pollock RF, Pohlmann J, Agirrezabal I, Sangro B. Health-related quality of life in patients with unresectable hepatocellular carcinoma treated with SIRT and nivolumab: a sub-analysis of the NASIR-HCC trial. J Patient Rep Outcomes. 2025 Apr 8;9(1):39. doi: 10.1186/s41687-025-00873-6.
• de la Torre-Alaez M, Matilla A, Varela M, Inarrairaegui M, Reig M, Lledo JL, Arenas JI, Lorente S, Testillano M, Marquez L, Da Fonseca L, Argemi J, Gomez-Martin C, Rodriguez-Fraile M, Bilbao JI, Sangro B. Nivolumab after selective internal radiation therapy for the treatment of hepatocellular carcinoma: a phase 2, single-arm study. J Immunother Cancer. 2022 Nov;10(11):e005457. doi: 10.1136/jitc-2022-005457.
• Ezponda A, Rodriguez-Fraile M, Morales M, Vivas I, De La Torre M, Sangro B, Bilbao JI. Hepatic Flow Redistribution is Feasible in Patients with Hepatic Malignancies Undergoing Same-Day Work-Up Angiography and Yttrium-90 Microsphere Radioembolization. Cardiovasc Intervent Radiol. 2020 Jul;43(7):987-995. doi: 10.1007/s00270-019-02371-x. Epub 2019 Dec 17.

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