Study of IMC-I109V in Non-cirrhotic HBeAg-negative Chronic HBV Infection

Prior treatment

• Changes in HBeAg status within 3 months prior to the screening visit
• Current or history of any clinically significant cardiac abnormalities/dysfunction, e.g. congestive heart failure, myocardial infarction ≤6 months prior to the screening visit, pulmonary hypertension, complex congenital heart disease, significant arrhythmia, or active cardiac ischemia.
• Receiving or planning to receive systemic immunosuppressive medications during the study or ≤ 2 months prior to Day1, including but not limited to prednisone >10 mg/day (or equivalent), methotrexate, cyclosporine, or interferon. NOTE: Local steroid therapy is allowed (eg, inhaled, otic, ophthalmic, or intra-articular medications)
• Treatment with any investigational drug or enrollment in any other clinical study ≤ 3 months prior to Day1, or at any time during participation in the study.
• Clinical diagnosis of substance abuse with alcohol, narcotics, or cocaine ≤12 months prior to the screening visit, except for those participants monitored in an opioid substitution maintenance program.
  • Part 3:
• Significant ongoing toxicity from prior anticancer treatment -
• Inadequate washout from prior anticancer therapy
• Prior cellular therapy for HBV-associated HCC
• Prior solid organ or bone marrow transplant
• Systemic antibiotics, vaccines or major surgery within 2-4 weeks prior to the first dose of study intervention

Other illness

• Known co-infection with any of the following: HIV, Hepatitis C virus, OR Hepatitis D virus
• Known HBV genotype A
• Gilbert's syndrome
• Any known pre-existing medical or psychiatric condition that could interfere with the participant's ability to provide informed consent or participate in study conduct, or that may confound study findings including, but not limited to: Immunologically-mediated disease, e.g. inflammatory bowel disease (Crohn's disease, ulcerative colitis), rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, scleroderma, or sarcoidosis within 5 years of the screening visit.
• Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding esophageal varices, hepatorenal syndrome, or hepatic encephalopathy.
• Significant immunosuppression from, but not limited to immunodeficiency conditions such as common variable hypogammaglobulinemia
• Use of any live vaccines against infectious diseases within 4 weeks of the first planned administration of study intervention or use of any non-live vaccines against infectious diseases within 2 weeks of the first planned administration of study intervention.
• Known HBV genotype A
• Decompensated liver disease
• Surgical intervention or local / loco-regional therapy for HBV HCC within 28 days of planned first dose of study treatment
• Active hepatitis C virus (HCV) infection
• Untreated HIV infection
• Significant secondary malignancy
• Clinically significant lung, heart, or autoimmune disease
• Hypersensitivity to study drug or excipients, or pre-medications

Lab values

• Out-of-range laboratory values, including ALT or AST > 3x upper limit of normal (ULN), total bilirubin and direct bilirubin > 1.5x ULN, Albumin ≤ 28 g/L, International normalized ratio (INR) > 1.3

Age

• Evidence of active or suspected malignancy, or a history of malignancy ≤3 years prior to the screening visit (except adequately treated carcinoma in situ, basal cell carcinoma of the skin, or stage 0 HCC that has been treated). NOTE: Participants under evaluation for malignancy are not eligible

Other

• Parts 1 and 2:
• Pregnant or lactating persons
• Pregnant or lactating persons
• Untreated or symptomatic CNS metastases
• Ascites requiring recurrent paracentesis
• Ongoing requirement for immunosuppressive treatment

• Parts 1 and 2:
• ≥18 to 65 years old at time of informed consent
• HLA-A*02:01 positive
• Documented evidence of CHB based on one of the following: a. Positive HBsAg and HBV DNA at least 6 months prior to the Screening visit; OR b. Historical liver biopsy consistent with CHB infection.
• Have been receiving entecavir and/or tenofovir (including tenofovir alafenamide) for ≥12months prior to screening and are willing to continue.
• HBV DNA negative at screening
• No history of liver cirrhosis AND prior assessment of fibrosis demonstrating non-cirrhotic status at screening
• Participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the trial screening date until 3 months after the final dose of the study intervention or longer if required by local regulations
  • Part 3:
• ≥18 years old at time of informed consent
• HLA-A*02:01 positive
• ECOG ≤1
• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology / cytology, or clinically by American Association for the Study of Liver Diseases criteria
• Failed or intolerant of ≥1 systemic therapy
• At least one measurable lesion (per RECIST 1.1) which is either not previously treated or, if treated, has clearly progressed prior to enrollment
• Documented evidence of CHB based on one of the following: a. Positive HBsAg and HBV DNA at least 6 months prior to the Screening visit; OR b. Historical liver biopsy consistent with CHB infection
• Life expectancy >3 months from time of enrolment
• Have compensated cirrhosis with a Child-Pugh score ≤ 7 (A or B7)
• On entecavir and/or tenofovir (disoproxil fumarate or alafenamide) with HBV DNA <100IU/ml at screening; willingness to continue for at least 6 months after the last dose of study drug
• Quantitative HBV surface antigen ≤ 5,000 IU/mL at screening
• Participants of childbearing potential who are sexually active with a non-sterilized partner must agree to use highly effective methods of birth control from the trial screening date until 3 months after the final dose of the study intervention or longer if required by local regulations