Brentuximab Vedotin and Nivolumab for the Treatment of Patients With Relapsed/Refractory Classical Hodgkin Lymphoma

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorizedrepresentative

• Assent, when appropriate, will be obtained per institutional guidelines

• Be willing to provide tissue (either from a fresh core or excisional biopsyperformed as standard of care, or from archival tissue) of a biopsy that wasperformed after frontline systemic therapy, and prior to starting protocol therapy

• If unavailable, exceptions may be granted with study principal investigator (PI) approval

• Eastern Cooperative Oncology Group (ECOG) =< 2

• Histologically confirmed diagnosis of classical Hodgkin lymphoma (excluding nodularlymphocyte predominant Hodgkin lymphoma) according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution

• Relapsed or refractory disease after no more than 1 line of prior therapy (notcounting radiotherapy). However, a maximum of 5 patients with primary refractorydisease may be enrolled in this study.

Note: Patients who received BV or an anti-PD-1/PD-L1 agent as part of frontline therapy are eligible if they achieved a CMR with frontline therapy and have not relapsed within 6 months from the end of frontline therapy Relapse must have been confirmed histologically (with hematopathology review at the participating institution)

• Not a candidate for ASCT, based on age, co-morbidities, or patient preference. Thereason for ASCT non-candidacy must be documented in the Case Report Form andverified by the site PI

• Measurable disease (at least one non-bony fludeoxyglucose F-18 [FDG]-avid lesion >= 1.5 cm in long axis)

• Absolute neutrophil count (ANC) >= 1,000/mm^3

• NOTE: Growth factor is not permitted within 7 days of ANC assessment unlesscytopenia is secondary to disease involvement

• Platelets >= 50,000/mm^3

• NOTE: Platelet transfusions are not permitted within 7 days of plateletassessment unless cytopenia is secondary to disease involvement

• Hemoglobin >= 8 g/dL (no transfusion allowed within 3 days prior to screening)

• Total bilirubin =< 1.5 x upper limit of normal (ULN) or direct bilirubin =< 1.5 xULN for patients with Gilbert's disease

• Aspartate aminotransferase (AST) =< 2.5 x ULN

• Alanine aminotransferase (ALT) =< 2.5 x ULN

• Creatinine clearance of >= 40 mL/min per 24 hour urine test or the Cockcroft-Gaultformula

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. Ifthe urine test is positive or cannot be confirmed as negative, a serum pregnancytest will be required

• Agreement by women and men of childbearing potential* to use an effective method ofbirth control or abstain from heterosexual activity for the course of the studythrough at least 5 months (women) or 7 months (men) after the last dose of protocoltherapy

• Childbearing potential defined as not being surgically sterilized (men andwomen) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

• Concomitant investigational therapy

• Live vaccine within 30 days prior to day 1 of protocol therapy (e.g. measles, mumps,rubella, varicella, yellow fever, rabies, bacillus Calmette-Guerin [BCG], oral poliovaccine, and oral typhoid)

• Grade >= 2 peripheral neuropathy

• History of prior >= grade 3 hypersensitivity to either brentuximab vedotin ornivolumab

• Known active central nervous system (CNS) involvement by lymphoma, includingparenchymal and/or lymphomatous meningitis

• History of another primary malignancy that has not been in remission for at least 3years, with the following exceptions:

• Non-melanoma skin cancer treated with curative intent

• In situ cervical cancer

• If the malignancy is expected to not require any treatment for at least 2 years (this exception should be discussed with the study PI)

• Condition requiring systemic treatment with either corticosteroids (> 10 mg dailyprednisone or equivalent) or other immunosuppressive medications within 14 days ofstudy drug administration. Exceptions are:

• Inhaled or topical steroids and

• Adrenal replacement doses > 10 mg daily prednisone equivalents in the absenceof active autoimmune disease

• History of progressive multifocal leukoencephalopathy (PML)

• Prior diagnosis of inherited or acquired immunodeficiency

• Active pneumonitis or interstitial lung disease

• Active, known or suspected autoimmune disease. The following are exceptions:

• Vitiligo

• Psoriasis not requiring systemic treatment

• Hemolytic anemia associated with the lymphoma

• Type I diabetes mellitus, if adequately controlled with therapy

• Thyroid disease, if adequately controlled with therapy

• Conditions not expected to recur in the absence of an external trigger (suchexceptions should be discussed with the study PI)

• Active history of:

• Hepatitis B (hepatitis B virus [HBV]) or C (hepatitis C virus [HCV]) infection.Patients with past HBV infection (defined as negative hepatitis B surfaceantigen [HBsAg] and positive hepatitis B core antibody [HBcAb]) are eligible ifHBV DNA is undetectable. Patients who are positive for HCV antibody areeligible if polymerase chain reaction (PCR) is negative for HCV ribonucleicacid (RNA)

• Human immunodeficiency virus (HIV) infection. Subjects who have an undetectableor unquantifiable human immunodeficiency virus (HIV) viral load with CD4 >= 200and are on highly active antiretroviral therapy (HAART) medication are allowed.Testing to be done only in patients suspected of having infections or exposures

• History of a cerebral vascular event (stroke or transient ischemic attack), unstableangina, myocardial infarction, or cardiac symptoms consistent with New York HeartAssociation class III-IV within 6 months prior to day 1 of protocol therapy

• Pregnant or breastfeeding

• Any other condition that would, in the Investigator's judgment, contraindicate thepatient's participation in the clinical study due to safety concerns with clinicalstudy procedures

• Prospective participants who, in the opinion of the investigator, may not be able tocomply with all study procedures (including compliance issues related tofeasibility/logistics)