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

Inclusion Criteria

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 HBVDNA at least 6 months prior to the Screening visit; OR b. Historical liver biopsyconsistent 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 demonstratingnon-cirrhotic status at screening

• Participants of childbearing potential who are sexually active with a non-sterilizedpartner must agree to use highly effective methods of birth control from the trialscreening date until 3 months after the final dose of the study intervention orlonger 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 byhistology / cytology, or clinically by American Association for the Study of LiverDiseases criteria

• Failed or intolerant of ≥1 systemic therapy

• At least one measurable lesion (per RECIST 1.1) which is either not previouslytreated or, if treated, has clearly progressed prior to enrollment

• Documented evidence of CHB based on one of the following: a. Positive HBsAg and HBVDNA at least 6 months prior to the Screening visit; OR b. Historical liver biopsyconsistent 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 lastdose of study drug

• Quantitative HBV surface antigen ≤ 5,000 IU/mL at screening

• Participants of childbearing potential who are sexually active with a non-sterilizedpartner must agree to use highly effective methods of birth control from the trialscreening date until 3 months after the final dose of the study intervention orlonger if required by local regulations

Exclusion Criteria:

Parts 1 and 2:

• Pregnant or lactating persons

• Known co-infection with any of the following: HIV, Hepatitis C virus, OR Hepatitis Dvirus

• Changes in HBeAg status within 3 months prior to the screening visit

• Known HBV genotype A

• Gilbert's syndrome

• Any known pre-existing medical or psychiatric condition that could interfere withthe participant's ability to provide informed consent or participate in studyconduct, 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 thescreening visit.

• Current or history of any clinically significant cardiac abnormalities/dysfunction,e.g. congestive heart failure, myocardial infarction ≤6 months prior to thescreening visit, pulmonary hypertension, complex congenital heart disease,significant arrhythmia, or active cardiac ischemia.

• Evidence of decompensated liver disease including, but not limited to, a history orpresence of clinical ascites, bleeding esophageal varices, hepatorenal syndrome, orhepatic encephalopathy.

• Significant immunosuppression from, but not limited to immunodeficiency conditionssuch as common variable hypogammaglobulinemia

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

• Receiving or planning to receive systemic immunosuppressive medications during thestudy or ≤ 2 months prior to Day1, including but not limited to prednisone >10mg/day (or equivalent), methotrexate, cyclosporine, or interferon. NOTE: Localsteroid therapy is allowed (eg, inhaled, otic, ophthalmic, or intra-articularmedications)

• Use of any live vaccines against infectious diseases within 4 weeks of the firstplanned administration of study intervention or use of any non-live vaccines againstinfectious diseases within 2 weeks of the first planned administration of studyintervention.

• 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 monthsprior to the screening visit, except for those participants monitored in an opioidsubstitution maintenance program.

Part 3:

• Pregnant or lactating persons

• Untreated or symptomatic CNS metastases

• Significant ongoing toxicity from prior anticancer treatment -

• Ascites requiring recurrent paracentesis

• Inadequate washout from prior anticancer therapy

• Prior cellular therapy for HBV-associated HCC

• Known HBV genotype A

• Decompensated liver disease

• Surgical intervention or local / loco-regional therapy for HBV HCC within 28 days ofplanned first dose of study treatment

• Active hepatitis C virus (HCV) infection

• Untreated HIV infection

• Significant secondary malignancy

• Clinically significant lung, heart, or autoimmune disease

• Ongoing requirement for immunosuppressive treatment

• Prior solid organ or bone marrow transplant

• Hypersensitivity to study drug or excipients, or pre-medications

• Systemic antibiotics, vaccines or major surgery within 2-4 weeks prior to the firstdose of study intervention

• 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