A Dose Finding and Safety Study of CC-220, Alone and in Combination With an Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Lymphomas

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Is ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Has histologically confirmed (per local evaluation) diagnosis of lymphoma according to 2016 World Health Organization (WHO) classification including:

   1. Cohort A: all subtypes including B-cell, T-cell and Natural killer (NK)-cell Non-Hodgkin lymphoma (NHL), and Classical Hodgkin lymphoma (cHL).
   2. Cohort B: all B-cell NHL.
   3. Cohort C: FL Grade 1-3a and MZL including extranodal marginal zone lymphoma (ENMZL) of mucosa-associated lymphoid tissue (MALT lymphoma), nodal marginal zone lymphoma (NMZL) and splenic marginal zone lymphoma (SMZL)
   4. Cohort D: aggressive B-cell lymphoma and FL grade 1-3a
   5. Cohort E: aggressive B-cell lymphoma including DLBCL NOS, high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements, Grade 3b FL and PMBCL
   6. Cohorts F and G: FL Grade 1 to 3a
3. Relapsed or refractory disease according to the following definitions:

   1. Aggressive B-cell lymphoma
   2. Follicular lymphoma (FL) and Marginal zone lymphoma (MZL): following at least 2 prior lines of systemic therapy (being previously exposed to at least 1 anti-CD20 mAb and 1 alkylating agent).
   3. Mantle cell lymphoma (MCL): following at least 2 prior lines of therapy including at least 1 immunochemotherapy and 1 bruton tyrosine kinase (BTK) inhibitor.
   4. Peripheral T-cell lymphoma (PTCL): following at least 2 prior lines of therapy OR after 1 prior line of standard therapy and being not eligible for any other approved regimen.
   5. Classical Hodgkin lymphoma (cHL): following at least 2 prior systemic lines of therapy and previously exposed to brentuximab vedotin and anti-PD1.
   6. All other subtypes: following at least 2 prior lines of therapy.
   7. Subjects previously treated with CAR-T therapy can be enrolled (irrespective of the indication).
4. Subjects must not be eligible for any other approved treatment for their underlying lymphoma as assessed by the Investigator.
5. Must have measurable disease defined by at least 1 fluorodeoxyglucose (FDG)-avid lesion for FDG-avid subtype and 1 bi-dimensionally measurable (\> 1.5 cm in longest diameter) disease by computed tomography (CT) or magnetic resonance imaging (MRI), as defined by the Lugano classification. Site of measurable disease cannot be previously irradiated.
6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
7. Must have the following laboratory values:

   1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L or ≥ 1.0 x 109/L
   2. Hemoglobin (Hb) ≥ 8 g/dL.
   3. Platelets (Plt) ≥ 75 x 109/L or ≥ 50 x 109/L
   4. Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase / serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x ULN.
   5. Serum total bilirubin ≤ 1.5 ULN except in cases of Gilbert's syndrome, then ≤ 3.0 ULN.
   6. Estimated serum creatinine clearance of ≥ 50 mL/min
8. All subjects must:

   1. Have an understanding that the study drug could have a potential teratogenic risk.
   2. Agree to follow all requirements defined in the Pregnancy Prevention Program for CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials.
9. Females of childbearing potential (FCBP1) must:

   a. Have 2 negative pregnancy tests as verified by the Investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment.
10. Male subjects must:

    1. Practice true abstinence2 or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study,

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Any significant medical condition, active infection (including severe acute respiratory syndrome coronavirus 2 \[SARS-CoV-2) suspected or confirmed, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Life expectancy ≤ 3 months.
4. Diagnosis of lymphoblastic lymphoma.
5. Aggressive lymphoma relapse requiring immediate cytoreductive therapy to avoid potential life-threatening consequences (eg, due to tumor location).
6. Prior Grade 3 or 4 infusion related reaction with rituximab (for Cohorts B, E and F) or obinutuzumab (for Cohorts C and G).
7. Prior therapy with the cereblon-modulating drug CC-99282.
8. Chronic systemic immunosuppressive therapy or corticosteroids.
9. Prior ASCT ≤ 3 months prior to starting CC-220 or \> 3 months AND with unresolved, Grade \> 1, treatment-related toxicity.
10. Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-220 or \> 6 months with unresolved, Grade \> 1, treatment-related toxicity.
11. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab or obinutuzumab.
12. Known allergy to thalidomide, pomalidomide or lenalidomide.
13. Inability or unwilling to undergo protocol required thromboembolism prophylaxis.
14. Major surgery ≤ 2 weeks prior to starting CC-220;
15. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).
16. Documented or suspected central nervous system (CNS) involvement of disease.
17. Subject with clinically significant cardiac disease.
18. Known seropositivity for or active viral infection with human immunodeficiency virus (HIV).
19. Known chronic active hepatitis B
20. History of other malignancy, unless the subject has been free of the disease for ≥ 3 years; exceptions to the ≥ 3-year time limit include history of the following:

    1. Incidental histologic finding of prostate cancer (or prostate cancer that has been treated with curative intent

Other protocol defined inclusion/exclusion criteria could apply