Clinical Trials /

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

NCT04663347

Description:

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

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: GCT3013-02
  • NCT ID: NCT04663347

Conditions

  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma

Interventions

DrugSynonymsArms
rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisoneR-CHOPArm 1 - Epcoritamab + R-CHOP
rituximab and lenalidomideR2Arm 2 - Epcoritamab + R- Lenalidomide
rituximab and bendamustineBRArm 3 - Epcoritamab + BR
rituximab, cisplatin, cytarabine, and dexamethasoneR-DHAX/CArm 4 - Epcoritamab + R-DHAX/C
gemcitabine and oxaliplatinGemOxArm 5 - Epcoritamab + GemOx
EpcoritamabGEN3013; DuoBody®-CD3xCD20Arm 1 - Epcoritamab + R-CHOP

Purpose

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

Detailed Description

      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, cisplatin, cytarabine, and dexamethasone (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

      For each arm, there are 2 parts: Part 1 (dose escalation) and Part 2 (expansion). Within each
      arm, subjects can only participate in one part.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1 - Epcoritamab + R-CHOPExperimentalEpcoritamab + R-CHOP in subjects with previously untreated DLBCL
  • rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
  • Epcoritamab
Arm 2 - Epcoritamab + R- LenalidomideExperimentalEpcoritamab + R- Lenalidomide in subjects with R/R FL
  • rituximab and lenalidomide
  • Epcoritamab
Arm 3 - Epcoritamab + BRExperimentalEpcoritamab + BR in subjects with previously untreated FL
  • rituximab and bendamustine
  • Epcoritamab
Arm 4 - Epcoritamab + R-DHAX/CExperimentalEpcoritamab + R-DHAX/C in subjects with R/R DLBCL Eligible ASCT
  • rituximab, cisplatin, cytarabine, and dexamethasone
  • Epcoritamab
Arm 5 - Epcoritamab + GemOxExperimentalEpcoritamab + GemOx in subjects with R/R DLBCL Ineligible ASCT
  • gemcitabine and oxaliplatin
  • Epcoritamab

Eligibility Criteria

        Inclusion Criteria

          1. Subject must sign an 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 CT or MRI

          4. ECOG PS score of 0, 1 or 2

          5. Acceptable organ function at screening

          6. CD20-positive 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

          9. Arm 1: Newly Diagnosed Documented 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 Documented DLBCL and ineligible for HDT-ASCT

          -  DLBCL, NOS

          -  "double-hit" or "triple-hit" DLBCL

          -  FL Grade 3B

        Exclusion Criteria

          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. Positive test results for HTLV-1

         10. Suspected active or latent tuberculosis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Escalation Phase - Number of dose-limiting toxicities (DLTs)
Time Frame:DLTs are evaluated during the first cycle (28 days) in each cohort
Safety Issue:
Description:To evaluate the safety of epcoritamab in combination with other agents

Secondary Outcome Measures

Measure:Pharmacokinetics concentration of epcoritamab
Time Frame:From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years
Safety Issue:
Description:To evaluate PK parameter - Clearance
Measure:Pharmacokinetics concentration of epcoritamab
Time Frame:From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years
Safety Issue:
Description:To evaluate PK parameter - Volume of distribution
Measure:Pharmacokinetics concentration of epcoritamab
Time Frame:From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years
Safety Issue:
Description:To evaluate PK parameter - AUC0-last (Area under the concentration-time curve (AUC) from time zero to last quantifiable sample)
Measure:Pharmacokinetics concentration of epcoritamab
Time Frame:From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years
Safety Issue:
Description:To evaluate PK parameter - Area under the concentration-time curve (AUC) from time zero to infinity
Measure:Pharmacokinetics concentration of epcoritamab
Time Frame:From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years
Safety Issue:
Description:To evaluate PK parameter - Cmax (maximum (peak) plasma drug concentration)
Measure:Pharmacokinetics concentration of epcoritamab
Time Frame:From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years
Safety Issue:
Description:To evaluatePK parameter - Tmax (time to reach maximum (peak) plasma concentration)
Measure:Pharmacokinetics concentration of epcoritamab
Time Frame:From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years
Safety Issue:
Description:To evaluate PK parameters - Predose values
Measure:Pharmacokinetics concentration of epcoritamab
Time Frame:From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years
Safety Issue:
Description:To evaluate PK parameters - t½ (elimination half-life)
Measure:Incidence of anti-drug antibodies (ADAs) to Epcoritamab
Time Frame:From start of treatment until end of treatment, approximately 24 months
Safety Issue:
Description:To evaluate immunogenicity
Measure:Duration of response (DOR)
Time Frame:Approximately 3 years after the last subject's first treatment
Safety Issue:
Description:To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Measure:Time to response (TTR)
Time Frame:Approximately 3 years after the last subject's first treatment
Safety Issue:
Description:To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Measure:Progressive-free survival (PFS)
Time Frame:Approximately 3 years after the last subject's first treatment
Safety Issue:
Description:To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Measure:Overall survival (OS)
Time Frame:Approximately 3 years after the last subject's first treatment
Safety Issue:
Description:To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Measure:Time to next anti-lymphoma therapy (TTNT)
Time Frame:Approximately 3 years after the last subject's first treatment
Safety Issue:
Description:To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Measure:Rate of minimal residual disease (MRD) negativity
Time Frame:Approximately 3 years after the last subject's first treatment
Safety Issue:
Description:To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Measure:Duration of minimal residual disease (MRD) negativity
Time Frame:Approximately 3 years after the last subject's first treatment
Safety Issue:
Description:To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Measure:Safety run-in only: preliminary anti-tumor activity as measured by the overall response rate
Time Frame:Approximately 3 years after the last subject's first treatment
Safety Issue:
Description:To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Measure:Expansion only: Monitor number and severity of AEs
Time Frame:Up to safety follow-up (up to 60days after last dose)
Safety Issue:
Description:To evaluate the safety and tolerability of epcoritamab in combination with other agents
Measure:Expansion only: Monitor number and severity of changes in laboratory values
Time Frame:Up to safety follow-up (up to 60days after last dose)
Safety Issue:
Description:To evaluate the safety and tolerability of epcoritamab in combination with other agents
Measure:Expansion only: Monitor number of dose interruptions and delays
Time Frame:Up to safety follow-up (up to 60days after last dose)
Safety Issue:
Description:To evaluate the safety and tolerability of epcoritamab in combination with other agents

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genmab

Last Updated

December 11, 2020