Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA UCSF
Dates
study started
estimated completion

Description

Summary

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 subjects with B-cell Non-Hodgkin Lymphoma (B-NHL).

Official Title

A Phase 1b/2, Open-Label Trial to Assess the Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Combination With Other Agents in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

Details

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 subjects with previously untreated diffuse large B-cell lymphoma (DLBCL) - Arm 2: epcoritamab + rituximab and lenalidomide (R2) in subjects with relapsed/refractory (R/R) follicular lymphoma (FL) - Arm 3: epcoritamab + rituximab and bendamustine (BR) in subjects with previously untreated FL - Arm 4: epcoritamab + rituximab, cytarabine, dexamethasone, and oxaliplatin/ carboplatin (R-DHAX/C) in subjects with R/R DLBCL eligible for autologous stem cell transplant (ASCT) - Arm 5: epcoritamab + gemcitabine and oxaliplatin (GemOx) in subjects with R/R DLBCL ineligible for ASCT due to age, performance status (PS), or comorbidity - Arm 6: epcoritamab + R2 in subjects with previously untreated FL - Arm 7: epcoritamab maintenance in subjects with FL who achieve a complete response (CR) or a partial response (PR) with SOC treatment - Arm 8: epcoritamab + reduced dose of R-CHOP (R mini-CHOP) in subjects with previously untreated DLBCL who are ineligible to receive full-dose anthracycline 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. Part 2 includes all 8 arms (Arm 1-8) and the primary goal of all arms, except Arm 7, is preliminary efficacy. For Arm 7, the primary goal is safety. Patients in Arm 1-5 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 patients in Arm 8 during a 28-day period ('safety-run phase'). The arms are conducted in parallel.

Keywords

Diffuse Large B-Cell Lymphoma Follicular Lymphoma DuoBody® monoclonal antibodies anti-CD3 anti-CD20 Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Gemcitabine Cytarabine Dexamethasone Prednisone Cyclophosphamide Bendamustine Hydrochloride Rituximab Carboplatin Doxorubicin Liposomal doxorubicin Oxaliplatin Vincristine Lenalidomide rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone rituximab and lenalidomide rituximab and bendamustine rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin gemcitabine and oxaliplatin Epcoritamab Epcoritamab Maintenance rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Subject must sign an Informed Consent Form (ICF)
  2. At least 18 years of age
  3. 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)
  4. Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
  5. Acceptable organ function at screening
  6. CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
  7. If of childbearing potential subject must practicing a highly effective method of birth control
  8. 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 Documented diffuse large B-cell lymphoma (DLBCL)
  • DLBCL, 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 DLBCL and eligible for HDT-ASCT
  • DLBCL, NOS
  • "double-hit" or "triple-hit" DLBCL
  • FL Grade 3B

Arm 5:

  • Relapsed or refractory documented 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:

  • DLBCL, NOS
  • T-cell/histiocyte rich DLBCL
  • "double-hit" or "triple-hit" DLBCL
  • FL Grade 3B

You CAN'T join if...

  1. Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
  2. Any prior treatment with a bispecific antibody targeting CD3 and CD20.
  3. Treatment with CAR-T therapy within 30 days prior to first dose of epcoritamab
  4. Clinically significant cardiovascular disease
  5. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
  6. 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
  7. Active positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
  8. Known history of seropositivity of human immunodeficiency virus (HIV)
  9. Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
  10. . Neuropathy > grade 1
  11. . Receiving immunostimulatory agent
  12. . Prior allogeneic HSCT
  13. . Current seizure disorder requiring anti-epileptic therapy

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

Locations

  • David Geffen School of Medicine at UCLA accepting new patients
    Los Angeles California 90095 United States
  • University of California San Francisco accepting new patients
    San Francisco California 94143 United States
  • Cedars-Sinai Medical Center accepting new patients
    Los Angeles California 90048 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Genmab
ID
NCT04663347
Phase
Phase 1/2 Research Study
Study Type
Interventional
Participants
Expecting 396 study participants
Last Updated