Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
completion around

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 (EPKINLY™) in combination with other standard of care (SOC) agents in participants with B-cell Non-Hodgkin Lymphoma (B-NHL).

The trial consists of 10 different treatment arms. Arm 9 (follicular lymphoma (FL)) is still open for enrolment of new patients, while the other arms have closed their recruitment.

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 participants with previously untreated diffuse large B-cell lymphoma (DLBCL)
  • Arm 2: epcoritamab + rituximab and lenalidomide (R2) in participants with relapsed/refractory (R/R) 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) with 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 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. Patients 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 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, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Lymphoma, Large B-Cell, Diffuse, Cytarabine, Dexamethasone, Prednisone, Cyclophosphamide, Bendamustine Hydrochloride, Ifosfamide, Rituximab, Carboplatin, Gemcitabine, Doxorubicin, Liposomal doxorubicin, Oxaliplatin, Etoposide, Vincristine, Lenalidomide, Etoposide phosphate, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, rituximab and lenalidomide, rituximab and bendamustine, rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin, gemcitabine and oxaliplatin, Epcoritamab, rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone, rituximab, ifosfamide, carboplatin, and etoposide phosphate, Epcoritamab + R-CHOP, Epcoritamab + R2, Epcoritamab + BR, Epcoritamab + R-DHAX/C, Epcoritamab + GemOx, Epcoritamab maintenance, Epcoritamab + R mini-CHOP, Epcoritamab + Lenalidomide, Epcoritamab + R-ICE

Eligibility

You can join if…

Open to people ages 18 years and up

  1. 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)
  2. Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
  3. Acceptable organ function at screening
  4. CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
  5. If of childbearing potential subject must practicing a highly effective method of birth control
  6. A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control

    Arm 1:

  7. Newly Diagnosed Documented diffuse large B-cell lymphoma (DLBCL)
  8. DLBCL, NOS
  9. "double-hit" or "triple-hit" DLBCL
  10. FL Grade 3B

    Arm 2: R/R FL Arm 3: Newly diagnosed, previously untreated FL grade 1-3A Arm 4:

  11. Documented DLBCL and eligible for HDT-ASCT
  12. DLBCL, NOS
  13. "double-hit" or "triple-hit" DLBCL
  14. FL Grade 3B

    Arm 5:

  15. Relapsed or refractory documented DLBCL and ineligible for HDT-ASCT
  16. DLBCL, NOS
  17. "double-hit" or "triple-hit" DLBCL
  18. FL Grade 3B

    Arm 6: Newly diagnosed, previously untreated FL grade 1-3A Arm 7:

  19. FL Grade 1-3A
  20. 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:

  21. DLBCL, NOS
  22. T-cell/histiocyte rich DLBCL
  23. "double-hit" or "triple-hit" DLBCL
  24. FL Grade 3B

    Arm 9:

  25. R/R FL
  26. Progressed within 24 months of initiating first-line treatment

    Arm 10:

  27. Documented DLBCL and eligible for HDT-ASCT
  28. DLBCL, NOS
  29. "double-hit" or "triple-hit" DLBCL
  30. 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

  • UCSF 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 662 study participants
Last Updated