First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma

Main Inclusion Criteria - Escalation Part (recruitment completed)

Documented CD20+ mature B-cell neoplasm

1. DLBCL - de novo or transformed
2. HGBCL
3. PMBCL
4. FL
5. MCL
6. SLL
7. MZL (nodal, extranodal or mucosa associated)
8. Relapsed, progressive and/or refractory disease following treatment with an anti-CD20 monoclonal antibody (e.g. rituximab) potentially in combination with chemotherapy and/or relapsed after autologous stem cell rescue.
9. ECOG performance status 0,1 or 2
10. Patients must have measurable disease by CT, MRI or PET-CT scan
11. Acceptable renal function
12. Acceptable liver function

Main Inclusion Criteria - Expansion & Optimization Parts

1. Documented CD20 positive mature B cell neoplasm or CD20+ MCL
2. DLBCL, de novo or transformed (including double hit or triple hit)
3. PMBCL
4. FL grade 3B
5. Histologic confirmed FL
6. MZL
7. SLL
8. MCL (prior BTKi or intolerant to BTKi)
9. At least 2 therapies including an anti-CD20 monoclonal antibody containing chemotherapy combination regimen
10. Either failed prior autologous hematopoietic stem cell transplantation or ineligible for autologous stem cell transplantation due to age or comorbidities
11. At least 1 measurable site of disease based on CT, MRI or PET-CT scan with involvement of 2 or more clearly demarcated lesions and or nodes

Main Exclusion Criteria - All Parts

1. Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening
2. Known past or current malignancy other than inclusion diagnosis
3. AST, and/or ALT >3 × upper limit of normal
4. Total bilirubin >1.5 × upper limit of normal, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
5. Estimated CrCl <45 mL/min
6. Known clinically significant cardiovascular disease
7. Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment). Past COVID-19 infection may be a risk factor
8. Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy
9. Seizure disorder requiring therapy (such as steroids or anti-epileptics)
10. Any prior therapy with an investigational bispecific antibody targeting CD3 and CD20
11. Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to first epcoritamab administration
12. Eligible for curative intensive salvage therapy followed by high dose chemotherapy with HSCT rescue
13. Autologous HSCT within 100 days prior to first epcoritamab administration, or any prior allogeneic HSCT or solid organ transplantation
14. Active hepatitis B (DNA PCR-positive) or hepatitis C (RNA PCR-positive infection). Subjects with evidence of prior HBV but who are PCR-negative are permitted in
15. Known human immunodeficiency virus (HIV) infection
16. Exposed to live or live attenuated vaccine within 4 weeks prior to signing ICF
17. Pregnancy or breast feeding
18. Patient is known or suspected of not being able to comply with the study protocol or has any condition for which, participation would not be in the best interest of the patient
19. Contraindication to all uric acid lowering agents

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.