Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With R/R B-NHL

Sponsor
Genmab (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04542824
Collaborator
AbbVie (Industry)
102
20
5
52.3
5.1
0.1

Study Details

Study Description

Brief Summary

The trial is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab in Japanese patients with relapsed, progressive or refractory B-cell lymphomas and Japanese patients with B-cell lymphomas that have achieved partial response (PR) or complete response (CR) following prior SOC. The trial consists of two parts: Part 1, dose escalation (phase 1), and Part 2, expansion (phase 2).

The purpose of the dose-escalation part of the trial is to determine the maximum tolerated dose (MTD) and the recommended Phase-2 dose (RP2D), as well as to establish the safety profile of epcoritamab in Japanese patients with relapsed, progressive or refractory B-cell lymphoma and Japanese patients with B-cell lymphomas that have achieved partial response (PR) or complete response (CR).

In the expansion part, additional patients will be treated with epcoritamab, at the RP2D and the purpose is to further explore and determine the safety and efficacy of epcoritamab.

Part 2 of the trial will be initiated once the RP2D has been determined in Part 1. In Part 2, epcoritamab is investigated as a monotherapy and in combination with other standard of care (SOC) agents.

Condition or Disease Intervention/Treatment Phase
  • Biological: epcoritamab (monotherapy)
  • Biological: epcoritamab
  • Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
  • Drug: gemcitabine and oxaliplatin
  • Biological: epcoritamab (maintenance)
  • Drug: rituximab and lenalidomide
Phase 1/Phase 2

Detailed Description

All participants in the trial will receive epcoritamab, as monotherapy or in combination with

SOC. The following regimens will be investigated in Part 2:

Arm 1: epcoritamab monotherapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL)

Arm 2: epcoritamab + rituximab and lenalidomide (R2) in patients with R/R FL

Arm 3: epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated DLBCL with high risk features

Arm 4: epcoritamab + gemcitabine and oxaliplatin (GemOx) in patients with R/R DLBCL who either failed prior autologous hematopoietic stem cell transplantation (ASCT), or are ineligible for autologous HSCT.

Arm 5: epcoritamab maintenance in patients with FL who achieve a complete response (CR) or a partial response (PR) following 1L/2L SOC treatment

Study Design

Study Type:
Interventional
Anticipated Enrollment :
102 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Part 1: Sequential Assignment Part 2: Parallel Group AssignmentPart 1: Sequential Assignment Part 2: Parallel Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3×CD20) in Japanese Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma - A Phase 1/2, Open-Label, Dose-Escalation Trial With Expansion Cohorts
Actual Study Start Date :
Aug 20, 2020
Anticipated Primary Completion Date :
Dec 30, 2024
Anticipated Study Completion Date :
Dec 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: arm 1: epcoritamab

In subjects with DLBCL/FL

Biological: epcoritamab (monotherapy)
Epcoritamab will be administered subcutaneously in cycles of 4 weeks (i.e. 28 days)
Other Names:
  • GEN3013; DuoBody®-CD3xCD20
  • Experimental: arm 2: epcoritamab + rituximab + lenalidomide

    In subjects with relapsed/refractory FL

    Biological: epcoritamab
    Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.
    Other Names:
  • GEN3013; DuoBody®-CD3xCD20
  • Drug: rituximab and lenalidomide
    28-day cycles.
    Other Names:
  • R2
  • Experimental: arm 3: epcoritamab + rituximab + cyclophosphamide+ doxorubicin+ vincristine + prednisone

    In subjects with previously untreated DLBCL

    Biological: epcoritamab
    Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.
    Other Names:
  • GEN3013; DuoBody®-CD3xCD20
  • Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
    21-day cycles
    Other Names:
  • R-CHOP
  • Experimental: arm 4: epcoritamab + gemcitabine + oxaliplatin

    In subjects with relapsed/refractory DLBCL

    Biological: epcoritamab
    Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.
    Other Names:
  • GEN3013; DuoBody®-CD3xCD20
  • Drug: gemcitabine and oxaliplatin
    28-day cycles
    Other Names:
  • Gemox
  • Experimental: arm 5: epcoritamab maintenance

    In subjects with FL in complete response (CR) or in partial response (PR) following first line or second line SOC treatment

    Biological: epcoritamab (maintenance)
    28-day cycle for Cycle 1 and then 56-day cycle from Cycle 2 through 13
    Other Names:
  • GEN3013; DuoBody®-CD3xCD20
  • Outcome Measures

    Primary Outcome Measures

    1. Part 1: Incidence and severity of Adverse Events (AEs) [From first dose until the end of the safety follow-up period (60 days after last dose)]

      Treatment emergent AEs.

    2. Part 1: Incidence of Dose limiting toxicities (DLTs) [DLTs are assessed during the first cycle (28 days) in each cohort]

      To determine the RP2D and the MTD, if reached.

    3. Part 2, Arm 1: Objective response rate (ORR) [From 6 weeks after enrollment until treatment discontinuation, assessed up to 3 years]

      Antitumor activity as measured by the ORR according to Lugano classification

    4. Part 2, Arms 2-4: Incidence of DLTs [DLTs are assessed during the first cycle (28 days) in arms 2-4]

    5. Part 2, Arms 2-5: Incidence and severity of AEs [From first dose until the end of the safety follow-up period (60 days after last dose)]

      Treatment emergent AEs (TEAEs)

    Secondary Outcome Measures

    1. Both parts: Area-under-the-concentration-time curve from Time 0 to Time of last dose (AUClast) [From first dose until treatment discontinuation, expected average of 1 year]

    2. Both parts: AUC from Time 0 to Infinity (AUCinf) [From first dose until treatment discontinuation, expected average of 1 year]

    3. Both parts: Maximum (peak) plasma concentration (Cmax) [From first dose until treatment discontinuation, expected average of 1 year]

    4. Both parts: Time to reach Cmax (Tmax) [From first dose until treatment discontinuation, expected average of 1 year]

    5. Both parts: Pre-dose (trough) concentrations (Cthrough) [From first dose until treatment discontinuation, expected average of 1 year]

    6. Both parts: Total body clearance of drug from the plasma (CL) [From first dose until treatment discontinuation, expected average of 1 year]

    7. Both parts: Volume of distribution (Vd) [From first dose until treatment discontinuation, expected average of 1 year]

    8. Both parts: Elimination half-life (t 1/2) [From first dose until treatment discontinuation, expected average of 1 year]

    9. Both parts: Incidence of Anti-Drug-Antibodies (ADAs) [From first dose until treatment discontinuation, expected average of 1 year]

    10. Part 1 and Part 2, Arm1: Number of participants with clinically significant shifts from baseline in clinical laboratory parameters [From first dose until treatment discontinuation, expected average of 1 year]

      Clinical laboratory parameters assessed: biochemistry, hematology

    11. Part 2, Arm1: Incidence and severity of AEs [From first dose until the end of the safety follow-up period (60 days after last dose)]

      TEAEs as assessed by CTCAE V5.0.

    12. Part 1 and Part 2, arms 2-5: ORR [Approximately 3 years after the last subject's first dose]

      Defined as proportion of participants who have a PR or CR following treatment with epcoritamab. Determined by the Lugano response criteria.

    13. Both parts: CR rate [Approximately 3 years after the last subject's first dose]

      Defined as proportion of participants with CR. Determined by the Lugano response criteria (both parts) and by the LYRIC response criteria (Part 2, arm 1). Response/disease progression in Part 2, arm 1 is reviewed by the IRC.

    14. Both parts: Duration of Response (DOR) [Approximately 3 years after the last subject's first dose]

      Defined as time from first documentation of response (CR or PR) to the date of progression of disease (PD) or death, whichever occurs earlier. Determined by the Lugano response criteria (both parts) and by the LYRIC response criteria (Part 2, arm 1). Response/disease progression in the expansion part is reviewed by the IRC.

    15. Both parts: Progression Free Survival (PFS) [Approximately 3 years after the last subject's first dose]

      Defined as time to first documented PD or death due to any cause. Determined by the Lugano response criteria (both parts) and by the LYRIC response criteria (Part 2, arm 1). Response/disease progression in the expansion part is reviewed by the IRC.

    16. Part 2: Duration of CR (DoCR) [Approximately 3 years after the last subject's first dose]

      Defined as time from first documentation of CR to the date of PD or death, whichever occurs earlier. Determined by the Lugano and LYRIC response criteria, assessed by the IRC

    17. Part 2: Time to Response (TTR) [Approximately 3 years after the last subject's first dose]

      Defined as time to first documentation of objective tumor response (PR or better). Determined by the Lugano and LYRIC response criteria, assessed by the IRC.

    18. Part 1 and Part 2 arm 1: Time to next anti-lymphoma therapy (TTNT) [Approximately 3 years after the last subject's first dose]

      Calculated as time to date of initiation of new anti-lymphoma therapy.

    19. Both parts: Overall Survival (OS) [Approximately 3 years after the last subject's first dose]

      Defined as time to death.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Main Inclusion Criteria:

    • Must be at least 20 years of age, inclusive

    • Japanese subjects

    • CD20 positivity at representative tumor biopsy

    1. Part 1:
    • Diffuse large B-cell lymphoma (de novo or histologically transformed)

    • High-grade B-cell lymphoma

    • Primary mediastinal large B-cell lymphoma

    • Follicular lymphoma

    • Marginal zone lymphoma (nodal, extranodal of mucosa-associated lymphoid tissue, or splenic)

    • Small lymphocytic lymphoma

    1. Part 2 :
    Arm 1:
    • Diffuse large B-cell lymphoma (de novo or histologically transformed)

    • Follicular lymphoma grade 1-3A

    • Relapsed or refractory disease and previously treated with at least 2 lines of systemic antineoplastic therapy including at least 1 anti-CD20 mAb-containing therapy.

    • Measurable disease by CT, MRI or PET-CT scan

    Arm 2:

    • R/R FL grade 1, 2 or 3a, stage II, III, or IV, without evidence of transformation.

    • Previously treated with at least 1 prior anti-neoplastic agent, including anti-CD20 antibody

    • Must have a need for treatment initiation based on symptoms and/or disease burden (GELF criteria)

    • Eligible to receive R2 per investigator determination

    Arm 3:
    • One of following confirmed histologies (de novo or histologically transformed from FL or nodal marginal zone lymphoma) :

    o DLBCL, NOS

    o "Double-hit" or "triple-hit" DLBCL

    • FL Grade 3B.

    • T-cell/histiocyte rich LBCL

    • International Prognostic Index (IPI) score ≥3

    • No prior therapy for DLBCL or FL G3B other than nodal biopsy, corticosteroids, or palliative radiotherapy.

    • Eligible to receive R-CHOP per investigator determination

    Arm 4:
    • One of following confirmed histologies (de novo or histologically transformed from FL or nodal marginal zone lymphoma) including:

    o DLBCL, NOS.

    o "Double-hit" or "triple-hit" DLBCL

    o FL Grade 3B.

    o T-cell/histiocyte rich LBCL

    • Relapsed or refractory to at least one prior therapy including at least one prior anti-CD20 antibody.

    • Either failed prior autologous hematopoietic stem cell transplantation (ASCT), or ineligible for autologous HSCT

    • Eligible to receive GemOx per investigator determination

    Arm 5:

    • History of histologically confirmed CD20+ FL Grade 1-3a without evidence of transformation.

    • In CR or PR per Lugano criteria following first-line or second-line treatment with SOC regimen, including anti-CD20 antibody, and last dose of SOC within 6 months prior to enrollment

    Main Exclusion Criteria:

    • Primary CNS lymphoma or CNS involvement by lymphoma at screening

    • Subjects not eligible for high dose therapy with autologous hematopoietic stem cell transplantation due to personal choice, social issues, or similar

    • Known clinically significant cardiac disease

    • Chronic ongoing infectious diseases requiring treatment (excluding prophylactic treatment)
    Exclusion criteria for Part 2, Arms 2 through 5:
    Arm 2:

    • FL Grade 3b

    • Histologic evidence of transformation to an aggressive lymphoma

    • Contraindication to rituximab or lenalidomide

    • Unwilling or unable to take aspirin prophylaxis or prophylactic anticoagulant as clinically indicated

    Arm 3:

    • Contraindication to any of the individual drugs of the R-CHOP regimen

    Arm 4:

    • Contraindication to any of the individual drugs of the GemOx regimen

    Arm 5:
    • FL Grade 3b

    • Histologic evidence of transformation to an aggressive lymphoma

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Genmab investigational site JP001 Chuo Ku Japan
    2 Genmab investigational site JP004 Fukuoka-shi Japan
    3 Genmab investigational site JP021 Fukushima-shi Japan
    4 Genmab investigational site JP006 Kagoshima-shi Japan
    5 Genmab investigational site JP019 Kanazawa-shi Japan
    6 Genmab investigational site JP009 Kashiwa-shi Japan
    7 Genmab investigational site JP010 Koto-Ku Japan
    8 Genmab investigational site JP020 Kyoto-shi Japan
    9 Genmab investigational site JP011 Matsuyama-shi Japan
    10 Genmab investigational site JP007 Nagoya-shi Japan
    11 Genmab investigational site JP008 Nagoya-shi Japan
    12 Genmab investigational site JP012 Nagoya-shi Japan
    13 Genmab investigational site JP014 Okayama-shi Japan
    14 Genmab Investigational site JP002 Osaka Japan
    15 Genmab investigational site JP005 Sendai-shi Japan
    16 Genmab investigational site JP017 Shinjuku-Ku Japan
    17 Genmab investigational site JP016 Suita-shi Japan
    18 Genmab investigational site JP015 Tsu-shi Japan
    19 Genmab investigational site JP018 Tsukuba-shi Japan
    20 Genmab investigational site JP003 Yamagata-shi Japan

    Sponsors and Collaborators

    • Genmab
    • AbbVie

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Genmab
    ClinicalTrials.gov Identifier:
    NCT04542824
    Other Study ID Numbers:
    • GCT3013-04 / EPCORE(TM) NHL-3
    • JapicCTI no 205408
    First Posted:
    Sep 9, 2020
    Last Update Posted:
    Jul 22, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 22, 2022