Liver Cancer Clinical Trials

• Age ≥ 18 years at time of signing Informed Consent.

• Has a diagnosis of hepatocellular carcinoma (HCC) documented radiologically by American Association for the Study of Liver Diseases (AASLD) criteria and/or histopathologically from a tumor biopsy.

• Has a treatment plan to receive a curative ablation (MWA only) or a curative surgical resection and ablation, or where the patient may benefit from surgery and ablation or ablation prior to receiving anti-cancer therapy.

• Has HCC with intermediate, high or very high risk of recurrence.

• Has hepatic only HCC (disease confined to the liver only), defined by no extra-hepatic lesions greater than 1 cm in size.

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

• Patient with past or ongoing hepatitis C virus (HCV) infection will be eligible if the patient has completed HCV treatment at least 1 month prior to Day 1.

• Patient with controlled hepatitis B will be eligible if the patient meets the following criteria:

‣ Antiviral therapy for hepatitis B virus (HBV) must be given for at least 4 weeks, and HBV viral load must be less than 500 IU/mL prior to treatment. Patients on active HBV therapy with viral loads under 500 IU/mL should stay on the same therapy throughout study treatment.

⁃ Patients who are hepatitis B core antibody (anti-HBc) positive, negative for HBsAg, and negative or positive for anti- HBs, and who have an HBV viral load under 500 IU/mL do not require HBV anti-viral prophylaxis.

• Patients who are not exposed to unreasonable risks by continued use of the investigational agent in spite of progression of disease. Such criteria may include the following:

‣ Absence of symptoms and signs indicating clinically significant progression of disease.

⁃ No decline in performance status, as measured by ECOG or Karnofsky or both.

⁃ Absence of symptomatic rapid disease progression requiring urgent medical intervention.

⁃ Ensure that patients are reconsenting to treatment with the Informed Consent clearly stating that retreatment is not standard of care.

• Has adequate organ function as specified in the Adequate Organ Function Laboratory Values Table. Specimens must be collected within 14 days prior to Day 1.

‣ Hematological: Absolute neutrophil count ≥1500/µL or ANC of ≤1500/µL if there is a stable medical history of neutropenia per provider discretion; Platelets ≥40,000/µL; Hemoglobin ≥8.0 g/dL.

⁃ Renal: Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR GFR ≥30 mL/min for patients with creatinine levels \>1.5 × institutional ULN

⁃ Hepatic: Total bilirubin ≤2 mg/dL OR direct bilirubin ≤ULN for patients with total bilirubin levels \>2 mg/dL; AST (SGOT) and ALT (SGPT) ≤5 × ULN; Albumin (c) \>2.6 g/dL

⁃ Coagulation: International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unless patient is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants

∙ Retreatment Inclusion Criteria:

• Patients receiving retreatment with IP-001 following intrahepatic recurrence must satisfy all of the following:

• Radiographic recurrence remains amenable to curative-intent thermal ablation.

• No symptomatic rapid disease progression requiring urgent systemic therapy or palliative intervention.

• ECOG performance status remains 0-2.

• No evidence of clinically significant hepatic decompensation.

• No extrahepatic disease that would preclude additional local therapy.

• The Investigator determines that additional thermal ablation remains clinically appropriate.

• The patient continues to satisfy protocol safety requirements.