Combination of TATE and PD-1 Inhibitor in Liver Cancer

The goal of the study is to investigate whether tumor necrosis induced by Trans-arterial Tirapazamine Embolization (TATE) treatment can boost anti-tumor immunity and enhance the therapeutic efficacy of immune checkpoint inhibitor. Patients with advanced liver cancers (primary HCC or metastatic gastric cancer) who have progressed on a prior immune checkpoint inhibitor will be enrolled in the study. Liver lesions will be treated with up to 4 TATE treatments for optimal debulking, which also serve as a vaccination process toward tumor. Lesion not treated with TATE will be used for monitoring the response toward a PD-1 inhibitor (Nivolumab) for abscopal effect. If a patient subsequently develops an "escape" to the PD-1 inhibitor, patient can have another 2 TATE treatments of the escaped tumor lesion. Dosing of the PD-1 inhibitor is per standard FDA-approved dosing schedule and continues until progressive disease. The efficacy will be assessed by the response rate (RR) using RECIST.

• Nivolumab Injectable Product (Drug), also known as OPDIVO: a PD-1 immune check inhibitor
• Trans-arterial tirapazamine embolization (Combination product): Embolization with Lipiodol and Gelfoam

Primary outcomes

• Overall Response Rate [up to 24 months]: Per RECIST 1.1 criteria

Secondary outcomes

• Duration of Response [up to 24 months]: From the date of image-demonstrated response to the date of progression
• Time to Progression [up to 24 months]: From randomization to disease progression or death
• Progression Free Survival [up to 24 months]: From randomization to disease progression or death
• Overall survival [through study completion, an average of 3 years]: From randomization to death

Sex: All, ages: 18 Years to 80 Years

1. Patients with a confirmed diagnosis of (1) advanced HCC or (2) metastatic gastric cancer.
2. Patients between ages 18 and 80
3. If HCC patients, they should have progressive disease (PD) on an immune therapy for advanced HCC. For patients with metastatic gastric cancer, they should have failed at least one line of systemic chemotherapy and an immune checkpoint inhibitor.
4. Patients with liver tumor lesions with at least one with a diameter of 2 cm or bigger, which is amendable for (super-)selective TATE as the target lesion.
5. ECOG score 2 or less
6. Child-Pugh scores 5-7 for HCC patients
7. All prior chemotherapy at least 4 weeks prior to study treatment. Immunotherapy not subject to this limitation.
8. No major GI bleeding in the prior 2 months.

8\. Hgb>=8, platelet >= 50,000, Cr =< 2, AST and ALT < 10 X ULN, t-Bilirubin < 3, 9. Patients with a history of major autoimmune disorders excluded.

• Liu CH, Peng CM, Hwang JI, Liang PC, Chen PJ, Abi-Jaoudeh N, Giiang LH, Tyan YS. Phase I Dose-Escalation Study of Tirapazamine Chemoembolization for Unresectable Early- and Intermediate-Stage Hepatocellular Carcinoma. J Vasc Interv Radiol. 2022 Aug;33(8):926-933.e1. doi: 10.1016/j.jvir.2022.04.031. Epub 2022 Apr 30. PMID 35504436
• Abi-Jaoudeh N, Dayyani F, Chen PJ, Fernando D, Fidelman N, Javan H, Liang PC, Hwang JI, Imagawa DK. Phase I Trial on Arterial Embolization with Hypoxia Activated Tirapazamine for Unresectable Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2021 May 17;8:421-434. doi: 10.2147/JHC.S304275. eCollection 2021. PMID 34041204

• Nadine Abi-Jaoudeh, MD, Principal investigator, UC Irvine Medical Center