Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

A Phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab in combination with other standard of care (SOC) agents in participants with B-NHL.

All participants in the trial will receive epcoritamab, as monotherapy or in combination. The following regimens will be investigated:

• Arm 1: epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with previously untreated diffuse large B-cell lymphoma (DLBCL)
• Arm 2: epcoritamab + rituximab and lenalidomide (R2) in participants with relapsed/refractory (R/R) follicular lymphoma (FL)
• Arm 3: epcoritamab + rituximab and bendamustine (BR) in participants with previously untreated FL
• Arm 4: epcoritamab + rituximab, cytarabine, dexamethasone, and oxaliplatin/ carboplatin (R-DHAX/C) in participants with R/R DLBCL eligible for autologous stem cell transplant (ASCT)
• Arm 5: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants with R/R DLBCL ineligible for ASCT due to age, performance status (PS), or comorbidity
• Arm 6: epcoritamab + R2 in participants with previously untreated FL
• Arm 7: epcoritamab maintenance in participants with FL who achieve a complete response (CR) or a partial response (PR) following first or second line SOC treatment
• Arm 8: epcoritamab + reduced dose of R-CHOP (R mini-CHOP) in participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline
• Arm 9: epcoritamab + lenalidomide for second-line treatment in participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy
• Arm 10: epcoritamab + rituximab, ifosfamide, carboplatin, and etoposide phosphate (R-ICE) in participants with R/R DLBCL eligible for ASCT

The trial consists of two parts: Part 1 ('Dose Escalation') and Part 2 ('Dose Expansion'). The primary objective of Part 1 is safety, and it includes Arm 1-5 and Arm 10. Part 2 includes all 10 arms (Arm 1-10) and the primary goal of all arms, except Arm 7, is preliminary efficacy. For Arm 7, the primary goal is safety. Participants in Arm 1-5 and Arm 10 can only participate in either Part 1 or Part 2. Dose Limiting Toxicities (DLTs) will be assessed in Part 1 and for a selected number of participants in Arm 8 during a 28-day period (safety run-in). The arms are conducted in parallel.

Key Inclusion Criteria

• Measurable disease defined as ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on computed tomography (CT) or magnetic resonance imaging (MRI). Applies to all arms except arm 7.
• Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
• Acceptable organ function at screening
• CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
• If of childbearing potential participant must practicing a highly effective method of birth control
• A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control

Arm 1:

• Newly diagnosed DLBCL
• DLBCL, not otherwise specified (NOS)
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Arm 2: R/R FL

Arm 3: Newly diagnosed, previously untreated FL grade 1-3A

Arm 4:

• Documented R/R DLBCL and eligible for HDT-ASCT
• DLBCL, NOS
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Arm 5:

• Documented R/R DLBCL and ineligible for HDT-ASCT
• DLBCL, NOS
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Arm 6: Newly diagnosed, previously untreated FL grade 1-3A

Arm 7:

• FL Grade 1-3A
• If PR or CR per Lugano criteria following first-line or second-line treatment with SOC regimen, and last dose of SOC within 6 months prior to enrollment.

Arm 8:

• Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline
• T-cell/histiocyte rich DLBCL
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Arm 9:

• R/R FL
• Progressed within 24 months of initiating first-line treatment

Arm 10:

• Documented R/R DLBCL and eligible for HDT-ASCT
• DLBCL, NOS
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Key Exclusion Criteria

• Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
• Any prior treatment with a bispecific antibody targeting CD3 and CD20.
• Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab
• Clinically significant cardiovascular disease
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
• CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture
• Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
• Known history of seropositivity of human immunodeficiency virus (HIV)
• Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
• Neuropathy > grade 1
• Receiving immunostimulatory agent
• Prior allogeneic HSCT
• Current seizure disorder requiring anti-epileptic therapy

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