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593 Efficacy of invariant natural killer T cell infusion plus transarterial embolization vs transarterial embolization alone for hepatocellular carcinoma patients: a phase 2 randomized clinical trial
  1. Jia Guo1,
  2. Xuli Bao2,
  3. Fuquan Liu3,
  4. Jiang Guo4,
  5. Yifan Wu3,
  6. Fang Xiong2 and
  7. Jun Lu1
  1. 1Capital Medical University, Fengtai District, Beijing, China
  2. 2Beijing YouAn Hospital, Capital Medical University, Beijing, Fengtai District, China
  3. 3Beijing Shijitan Hospital, Capital Medical University, Beijing, Haidian District, China
  4. 4Beijing Ditan Hospital, Capital Medical University, Beijing, Chaoyang District, China
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Hepatocellular carcinoma remains a leading cause of mortality worldwide, accounting for over three quarter of a million deaths annually.1 While transarterial chemoembolization (TACE) therapy is the current first-line intervention for the roughly 70–80% of cases which are non-resectable,2–6 repeated treatments quickly lead to recalcitrance in recurring tumors, and 5-year survival rates linger at an abysmal 18%.7 The results of our phase 1 trial indicated that autologous iNKT cell therapy has good tolerability in HCC patients and could potentially further improve outcomes.8

Methods This randomized, multicenter, open-label phase 2 trial was conducted at Beijing Youan, Beijing Shijitan, and Beijing Ditan Hospital of Capital Medical University between March 2018 and March 2020.Follow-up was completed on July 20, 2020. The cohort comprised 54 Barcelona Clinic Liver Cancer (BCLC) B/C stage patients with HCC after TACE failure. Efficacy analyses were conducted in the modified intention-to-treat population. Eligible patients were randomly assigned (1:1) to receive either transarterial embolization (TAE) therapy (TAE group) or a combination of TAE (weeks 0 and 4) plus iNKT cell infusion (6~9×107 cells/m2 intravenously) every 2 weeks starting week 1 (TAE-iNKT group). To exclude compromising iNKT cells, TAE was used instead of TACE. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), peripheral blood cell count, and safety.

Results Fifty-four patients completed the study (table 1). Median PFS was significantly higher in TAE-iNKT patients (5.7 months [95% CI, 4.3–7.0 months]) compared with TAE patients (2.7 months [95% CI, 2.3–3.2 months]; hazard ratio 0.32 [95% CI, 0.16–0.63]; P<0.001) (figure 1). Higher objective response rate (ORR) and disease control rate (DCR) were observed in TAE-iNKT patients (52% and 85%, respectively) compared with TAE patients (11% and 33%; respectively)(table 2). Five TAE-iNKT patients and 1 TAE patient achieved completed response (figure 3). Median time to deterioration in QoL was longer in TAE-iNKT patients (9.2 months [95% CI, 6.0–13.3 months]) compared with TAE patients (3.0 months [95% CI, 2.9–3.0 months]) (figure 2). The mean lymphocytes were higher in the TAE-iNKT group than in the TAE group at 8 (1.48 vs. 0.95×109/L, P=.007) and 12 (1.49 vs. 0.89×109/L, P=.001) weeks (figure 4). Grade 3 adverse events occurred in 1 TAE-iNKT patient (4%) and 5 TAE patients (19%). All other adverse events were grade 1–2(table 3).

Conclusions iNKT cell infusion significantly improved PFS, ORR, DCR, and QoL with manageable toxicity during TAE therapy in patients with HCC.

Acknowledgements This study was funded by Capital Health Research and Development Projects (grant number: 2018-1-2181), the Original Exploration Program of the National Natural Science Foundation of China (grant number: 82150110), and the Beijing Municipal Administration of Hospitals Incubating Program (grant number: PX2019063). Nonfinancial support: iNKT cell was sponsored by the GeneKey GMP Lab.

Trial Registration Identifier: NCT04011033


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  7. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA: a cancer journal for clinicians. Jan 2020;70(1):7−30.

  8. Gao Y, Guo J, Bao X, et al. Adoptive Transfer of Autologous Invariant Natural Killer T Cells as Immunotherapy for Advanced Hepatocellular Carcinoma: A Phase I Clinical Trial. Oncologist. Nov 2021;26(11): e1919−e1930.

Ethics Approval The study protocol and consent form were approved by the ethics committee of Beijing Youan Hospital (Jing You Ke Lun [2018] No. 016), and the other two participating units were subject to ethical examination and approval of the lead unit.

Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal

Abstract 593 Table 1

Patient demographic and disease characteristics

Abstract 593 Table 2

Response to autologous iNKT cell infusion

Abstract 593 Table 3

Adverse events

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