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Clinical Trial
. 2024 Mar 4;29(3):270-e413.
doi: 10.1093/oncolo/oyad331.

A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma

Shawn Yu  1 , Menggang Yu  2 , Barry Keane  1 , David M Mauro  1 , Paul R Helft  3 , William P Harris  4 , Hanna K Sanoff  1 , Matthew S Johnson  5 , Bert O'Neil  6 , Autumn Jackson McRee  7 , Ashwin Somasundaram  1
Affiliations
Clinical Trial

A Pilot Study of Pembrolizumab in Combination With Y90 Radioembolization in Subjects With Poor Prognosis Hepatocellular Carcinoma

Shawn Yu et al. Oncologist. .

Abstract

Background: Combination checkpoint inhibition therapy with yttrium-90 (Y90) radioembolization represents an emerging area of interest in the treatment of advanced hepatocellular carcinoma (HCC). HCRN GI15-225 is an open-label, single-arm multicenter, pilot study (NCT03099564).

Methods: Eligible patients had poor prognosis, localized HCC defined as having portal vein thrombus, multifocal disease, and/or diffuse disease that were not eligible for liver transplant or surgical resection. Patients received pembrolizumab 200 mg intravenously every 3 weeks in conjunction with glass yttrium-90 (Y90) radioembolization TheraSphere. Primary endpoint was 6-month progression-free survival (PFS6) per RECIST 1.1. Secondary endpoints included time to progression (TTP), objective response rate (ORR), overall survival (OS), and safety/tolerability.

Results: Between October 23, 2017 and November 24, 2020, 29 patients were enrolled: 2 were excluded per protocol. Fifteen of the remaining 27 patients were free of progression at 6 months (55.6%; 95% CI, 35.3-74.5) with median PFS 9.95 months (95% CI, 4.14-15.24) and OS 27.30 months (95% CI, 10.15-39.52). One patient was not evaluable for response due to death; among the remaining 26 patients, ORR was 30.8% (95% CI, 14.3-51.8) and DCR was 84.6% (95% CI, 65.1-95.6).

Conclusion: In patients with localized, poor prognosis HCC, pembrolizumab in addition to glass Y90 radioembolization demonstrated promising efficacy and safety consistent with prior observations (ClinicalTrials.gov Identifier: NCT03099564; IRB Approved: 16-3255 approved July 12, 2016).

Keywords: TARE; glass Y90 radioembolization; hepatocellular carcinoma; immunotherapy; pembrolizumab.

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Conflict of interest statement

Shawn Yu reported ownership interests and intellectual property rights with Neoleukin Therapeutics. William P. Harris reported advisory relationships with Merck, Boston Scientific, and ICON Clinical Research; research funding (to institution) from BMS, Medimmune, Merck, Boston Scientific, Koo Foundation, Zymeworks, and Sanofi Pasteur; and expert testimony for Boston Scientific and Merck. Hanna K. Sanoff reported research funding from AstraZeneca, Merck, Bristol Myers Squibb, BioMed Valley Discoveries, Exelixis, Rgenix, Pfizer, and F Hoffman La Roche. Matthew S. Johnson is a member of the Boston Scientific Advisory Board. Ashwin Somasundaram reported a consulting/advisory relationship with Taiho. The other authors indicated no financial relationships.

Figures

Figure 1.
Figure 1.
Patient flow diagram.
Figure 2.
Figure 2.
Kaplan–Meier curves for TTP (top), PFS (middle), and OS (bottom).
Figure 3.
Figure 3.
Waterfall plots for target lesion size change from baseline based on RECIST (top) and mRECIST (bottom). PFS and mPFS times are listed for all patients. Patients with right censored PFS or mPFS data are indicated with a ">" in front of the time.
Figure 4.
Figure 4.
Subgroup analyses of percent of patients progression free at 6 months (top) and objective response as a percent (bottom).
Figure 5.
Figure 5.
ITT TTP curve: based on 27 patients (Pt 1026 and 1031 had missing progression data). Median TTP is 9.95 months with 95% CI (4.14, 18.56).
Figure 6.
Figure 6.
ITT PFS curve: based on 28 patients (Pt 1026 had missing PFS data). Median PFS is 9.95 months with 95% CI (4.11, 15.24).
Figure 7.
Figure 7.
ITT OS curve: based on 29 patients in the ITT population. Median OS is 30 months with 95% CI (12.9, ---). The upper bound was not calculable due to insufficient follow-up for survival.
Figure 8.
Figure 8.
Waterfall plot based on RECIST in the ITT population.
Figure 9.
Figure 9.
Waterfall plot based on mRECIST in the ITT population.
See this image and copyright information in PMC

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