Safety and Immunotherapeutic Activity of Cemiplimab in Participants With HBV on Suppressive Antiviral Therapy

Inclusion Criteria: * Chronic HBV infection (defined as hepatitis B surface antigen \[HBsAg\] positive). * Receiving treatment at the time of study entry and for ≥12 months prior to study entry with HBV-active nucleos(t)ides, with tenofovir- or entecavir-containing therapy: tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), TDF/emtricitabine (FTC), TAF/FTC, or entecavir. * Ability and willingness of participant to provide informed consent. * Ability and willingness of participant to continue HBV antiviral therapy throughout the study. * Weight ≥40 kg and \<200 kg. * Evidence of limited or no evidence of fibrosis (F0-F2) by liver biopsy or non-invasive alternative, as defined in the study protocol. * The following laboratory values obtained within 60 days prior to study entry: * HBV DNA level \<20 IU/mL * Documentation of hepatitis B e antigen (HBeAg) status (positive or negative) * Hemoglobin ≥14.0 g/dL for male, ≥12.0 g/dL for female participants * Platelets ≥150,000/mm\^3 * Absolute neutrophil count (ANC) \>1500/mm\^3 * International normalized ratio (INR) ≤1.1 * Albumin ≥3.5 g/dL * Creatinine Clearance ≥60 mL/min, as calculated by the Cockcroft-Gault equation * NOTE: A calculator for the Cockcroft-Gault equation is available on the Data Management Center (DMC) website at www.fstrf.org. * Aspartate aminotransferase (AST) serum glutamic:oxaloacetic transaminase (SGOT) \<1.25 x ULN * ALT serum glutamic:pyruvic transaminase (SGPT) \<1.25 x ULN * Direct bilirubin ≤1.0 x ULN * AM cortisol \>10 mcg/dL and \<ULN * NOTE A: Female participants on estrogen-containing oral contraception or other exogenous estrogen treatment may repeat the AM cortisol as part of screening to determine eligibility. AM cortisol should be drawn prior to 12 noon or per local lab requirements. * NOTE B: Participants with a low cortisol level that was drawn after 10:00 AM may repeat the AM cortisol as part of screening to determine eligibility. * Normal creatinine phosphokinase (CPK) level * Thyroid stimulating hormone (TSH) and free thyroxine (T4) level within normal limits * Fasting blood glucose \<126 mg/dL * Interferon-gamma release assay (IGRA) for tuberculosis (TB) with negative results within 90 days prior to study entry, OR prior positive TB IGRA or positive purified protein derivative (PPD) skin test with documented evidence of completed prophylaxis treatment. * HCV antibody negative result within one year prior to study entry; or if the participant is HCV antibody positive, an unquantifiable HCV RNA result (\< lower limit of quantification \[LLOQ\], either target detected, or target not detected) within 60 days prior to study entry. * Documentation of completion of SARS-CoV-2 vaccine series and up-to-date additional or booster immunizations, as recommended by local country guidance * Participants of reproductive potential, a negative urine or serum pregnancy test at screening, and again within 48 hours prior to study entry by any US clinic or laboratory that has CLIA certification or its equivalent, or is using a point of care (POC)/ CLIA-waived test, or at any Network-approved non-US laboratory or clinic that operates in accordance with GCLP and participates in appropriate EQA programs * All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, oocyte donation, in vitro fertilization). * When participating in sexual activity that could lead to pregnancy, participants must agree to use at least two reliable forms of contraceptive simultaneously, over the time period of 36 weeks following study entry (to include time period up to 6 months after last infusion). Such methods include: * Condoms (male or female) with or without a spermicidal agent * Diaphragm or cervical cap with spermicide * Intrauterine device (IUD) * Tubal ligation * Hormone-based contraceptive * NOTE: Providers and participants should be advised that not all contraceptive choices listed above can prevent HBV transmission. Study participants who are sexually active with HBV negative or unknown HBV serostatus partners should be advised that they need to consider effective strategies to reduce the risk of HBV transmission and meet the requirement for effective contraception during their participation in the study. Study participants should discuss contraceptive choices and HBV risk-reduction methods with their health care provider. * Participants who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy or men who have documented azoospermia) are eligible without requiring the use of contraceptives. Acceptable documentation of menopause or sterilization is specified below. * Written or oral documentation communicated by clinician or clinician's staff of one of the following: * Physician report/letter * Operative report or other source documentation in the patient record (a laboratory report of azoospermia is required to document successful vasectomy) * Discharge summary * Follicle stimulating hormone-release factor (FSH) measurement elevated into the menopausal range as established by the reporting laboratory * Intention to comply with the dosing instructions for study drug administration and ability to complete the study schedule of assessments. Exclusion Criteria * Any malignancy within the 5 years prior to study entry or current malignancy requiring cytotoxic therapy. * NOTE: A history of non-melanoma skin cancer (e.g., basal cell carcinoma or squamous cell skin cancer) at any time is not exclusionary. * Current chronic, acute, or recurrent bacterial, fungal, or viral (other than HBV) infections that are serious, in the opinion of the site investigator, and that required systemic therapy within 30 days prior to study entry. * Prior history of or active autoimmune disorders including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis, adrenal insufficiency, hypothyroidism and/or hyperthyroidism, autoimmune thyroiditis, hypophysitis, multiple sclerosis, or sarcoidosis. * NOTE: For questions related to the definition of autoimmune disorders, sites should contact the team per the study protocol. * Any known acquired or congenital immune deficiency. * History of chronic obstructive pulmonary disease (COPD). * History of significant pulmonary conditions. * Unstable asthma (e.g., sudden acute attacks occurring without an obvious trigger) or asthma requiring: * Daily steroid or long-acting beta-agonist prevention * Hospitalization in the 2 years prior to entry * A history of chronic congestive heart failure or other significant cardiac condition. * Any active clinically significant medical condition that, in the opinion of the site investigator, would place the participant at increased risk. * History of non-infectious pneumonitis within the last 5 years prior to study entry. * Retinopathy or uveitis within 180 days prior to study entry. * Any acute or chronic psychiatric diagnoses that, in the opinion of the investigator, make the participant ineligible for participation. * Any vaccination within 30 days prior to entry with the exception of SARS-CoV-2 vaccination.. * NOTE: Individuals who require vaccination must delay screening for the study until 30 days after receiving the last injection. * Human immunodeficiency virus (HIV) infection. * Evidence of current (within 1 year prior to entry) Hepatitis delta virus (HDV) infection (HDV antibody positive). * Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 30 days prior to study entry. * Alpha-Fetoprotein (AFP) \>100 within 60 days prior to study entry in the absence of imaging within the prior 6 months prior to study entry to exclude hepatocellular carcinoma (HCC). * Any known bleeding disorder (i.e., hemophilia). * Receipt of investigational drug or device within 6 months prior to study entry. * History of treatment with a phosphoinositide 3-kinase inhibitor, including idelalisib. * History of checkpoint inhibitor treatment including anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1) or anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) antibodies. * History of immunoglobulin IgG therapy. * Receipt of interferon (IFN) therapy within 12 months prior to study entry. * Use of immunomodulators (e.g., interleukins, cyclosporine), systemic cytotoxic chemotherapy, or corticosteroid therapy. * NOTE A: Participants receiving topical corticosteroids will not be excluded. * NOTE B: Participants receiving inhaled corticosteroids will be excluded. * Intent to use immunomodulators (e.g., IL-2, IL-12, interferon \[IFNs\], or TNF modifiers) or corticosteroids (other than topical steroids) during the course of the study. * Current HCV antiviral therapy or receipt of HCV treatment in the 6 months prior to study entry. * Use of anticoagulants within the 30 days prior to study entry. * Prior treatment with other immune modulating agents that was associated with toxicity that resulted in discontinuation of the immune-modulating agent. * Current use or intent to use biotin ≥5 mg/day, including within dietary supplements during the study. * NOTE: Please see the study protocol for a list of other names used for biotin that should be looked for on the labels of dietary supplements. * Positive thyroid peroxidase (TPO) antibody result within 60 days prior to study entry. * Positive glutamic acid decarboxylase antibody (GAD65 Ab) result within 60 days prior to study entry. * Positive islet cell antibody result within 60 days prior to study entry. * Positive antinuclear antibody (ANA) ≥1:80 within 60 days prior to study entry. * Anti-smooth muscle antibody \>1:80 within 60 days prior to study entry. * Immunoglobulin G (IgG) ≥1.2 x ULN within 60 days prior to study entry. * Known allergy/sensitivity or any hypersensitivity to components of cemiplimab (anti-PD-1) or its formulation or previous mAb treatments. * Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. * Breastfeeding or pregnancy. * A male participant with a pregnant female sexual partner. * For participants in the optional leukapheresis (LA) component, prior history of difficulty establishing venous access or current contraindication for LA, in the opinion of the site investigator and based on pre-LA assessments listed in the study protocol. * NOTE: Participants unwilling or unable to complete LA are still eligible for enrollment into the main study. * Participants with a history of solid organ transplant.