Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With R/R B-NHL (EPCORE™ NHL-3)

• ClinicalTrials.gov Identifier: NCT04542824
• Recruitment Status: Active, not recruiting
• First Posted: September 9, 2020
• Last Update Posted: May 7, 2024
• Sponsor: Genmab
• Collaborator: AbbVie
• Information provided by (Responsible Party): Genmab

Study Description

Brief Summary:

The trial is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab (EPKINLY™) 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
Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; Primary Mediastinal Large B Cell Lymphoma; Follicular Lymphoma; Marginal Zone Lymphoma; Small Lymphocytic Lymphoma	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 (Clinical Trial)
• Estimated Enrollment: 102 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment

Intervention Model Description

Part 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: August 20, 2020
• Estimated Primary Completion Date: December 30, 2024
• Estimated Study Completion Date: December 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; EPKINLY™
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; EPKINLY™; Drug: rituximab and lenalidomide; 28-day cycles.; Other Name: 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; EPKINLY™; Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; 21-day cycles; Other Name: 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; EPKINLY™; Drug: gemcitabine and oxaliplatin; 28-day cycles; Other Name: 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; EPKINLY™

Outcome Measures

Primary Outcome Measures :

1. Part 1: Incidence and severity of Adverse Events (AEs) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: DLTs are assessed during the first cycle (28 days) in arms 2-4 ]
5. Part 2, Arms 2-5: Incidence and severity of AEs [ Time Frame: 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) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
2. Both parts: AUC from Time 0 to Infinity (AUCinf) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
3. Both parts: Maximum (peak) plasma concentration (Cmax) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
4. Both parts: Time to reach Cmax (Tmax) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
5. Both parts: Pre-dose (trough) concentrations (Cthrough) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
6. Both parts: Total body clearance of drug from the plasma (CL) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
7. Both parts: Volume of distribution (Vd) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
8. Both parts: Elimination half-life (t 1/2) [ Time Frame: From first dose until treatment discontinuation, expected average of 1 year ]
9. Both parts: Incidence of Anti-Drug-Antibodies (ADAs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Approximately 3 years after the last subject's first dose ]
    Defined as time to death.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

2. 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

Japan

National Cancer Center Hospital

Chuo Ku, Japan

National Hospital Organization Kyushu Cancer Center

Fukuoka-shi, Japan

Fukushima Medical University Hospital

Fukushima-shi, Japan

Kagoshima University Hospital

Kagoshima-shi, Japan

National Cancer Center Hospital East

Kashiwa-shi, Japan

Cancer Institute Hospital of JFCR

Koto-Ku, Japan

Kyoto University Hospital

Kyoto-shi, Japan

Matsuyama Red Cross Hospital

Matsuyama-shi, Japan

Aichi Cancer Center Hospital

Nagoya-shi, Japan

NHO Nagoya Medical Center

Nagoya-shi, Japan

Kindai University Hospital

Osaka, Japan

Tokyo Medical University Hospital

Shinjuku-Ku, Japan

Osaka University Hospital

Suita-shi, Japan

Yamagata University Hospital

Yamagata-shi, Japan

Sponsors and Collaborators

Genmab

AbbVie

More Information

• Responsible Party: Genmab
• ClinicalTrials.gov Identifier: NCT04542824
• Other Study ID Numbers: GCT3013-04; JapicCTI no 205408 ( Registry Identifier: JAPIC )
• First Posted: September 9, 2020
• Last Update Posted: May 7, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Prednisone; Cyclophosphamide; Rituximab; Gemcitabine; Doxorubicin; Oxaliplatin; Vincristine; Lenalidomide; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents