Clinical trial NCT04542824: Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (R/R B-NHL)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B Cell Lymphoma
High-grade B-cell Lymphoma
Primary Mediastinal Large B Cell Lymphoma
Follicular Lymphoma
Marginal Zone Lymphoma
Small Lymphocytic Lymphoma
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: AbbVie
First posted: 2020-09-09
Enrollment: 78
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1: Sequential Assignment

Part 2: Parallel Group Assignment
Primary purpose: TREATMENT

Brief summary: The trial is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab (EPKINLY™) in Japanese participants with relapsed, progressive or refractory B-cell lymphomas and Japanese participants with B-cell lymphomas that have achieved partial response (PR) or complete response (CR) following prior standard of care (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 participants with relapsed, progressive or refractory B-cell lymphoma and Japanese participants with B-cell lymphomas that have achieved PR or CR.

In the expansion part, additional participants 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 SOC agents.

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 participants with R/R FL

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

Arm 4: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants 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 participants with FL who achieve a CR or a PR following first line (1L)/second line (2L) SOC treatment

Eligibility criteria: Main Inclusion Criteria:

• Must be at least 20 years of age, inclusive

• Japanese participants

• 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 monoclonal antibody (mAb)-containing therapy.
   * Measurable disease by computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (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 (Groupe d'Etude des Lymphomes Folliculaires \[GELF\] 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, not otherwise specified (NOS)
     * "Double-hit" or "triple-hit" DLBCL
     * FL Grade 3B.
     * T-cell/histiocyte rich large B-cell lymphoma (LBCL)
   * International Prognostic Index (IPI) score ≥3
   * No prior therapy for DLBCL or FL grade 3B (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
     * FL Grade 3B.
     * 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 hematopoietic stem-cell transplantation (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 central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening

   • Participants 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

Primary outcomes:
measure: Part 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose until the end of the safety follow-up period (60 days after last dose), up to approximately 5 years
measure: Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: DLTs are assessed during the first cycle (28 days) in each cohort
measure: Part 2, Arm 1: Objective Response Rate (ORR)
timeFrame: Up to 1.5 years
measure: Part 2, Arms 2-4: Number of Participants with DLTs
timeFrame: DLTs are assessed during the first cycle (28 days) in arms 2-4
measure: Part 2, Arms 2-5: Number of Participants with TEAEs
timeFrame: From first dose until the end of the safety follow-up period (60 days after last dose), up to approximately 5 years
Secondary outcomes:
measure: Both parts: Area-under-the-concentration-time curve from Time 0 to Time of last dose (AUClast)
timeFrame: From first dose until treatment discontinuation, expected average of 1 year
measure: Both parts: AUC from Time 0 to Infinity (AUCinf)
timeFrame: From first dose until treatment discontinuation, expected average of 1 year
measure: Both parts: Maximum (Peak) Plasma Concentration (Cmax)
timeFrame: From first dose until treatment discontinuation, expected average of 1 year
measure: Both parts: Time to Reach Cmax (Tmax)
timeFrame: From first dose until treatment discontinuation, expected average of 1 year
measure: Both parts: Pre-dose (Trough) Concentrations (Cthrough)
timeFrame: From first dose until treatment discontinuation, expected average of 1 year
measure: Both parts: Total Body Clearance of Drug from the Plasma (CL)
timeFrame: From first dose until treatment discontinuation, expected average of 1 year
measure: Both parts: Volume of Distribution (Vd)
timeFrame: From first dose until treatment discontinuation, expected average of 1 year
measure: Both parts: Elimination Half-life (t 1/2)
timeFrame: From first dose until treatment discontinuation, expected average of 1 year
measure: Both parts: Number of Participants with Anti-Drug-Antibodies (ADAs)
timeFrame: From first dose until treatment discontinuation, expected average of 1 year
measure: Part 2, Arm 1: Number of Participants with TEAEs
timeFrame: From first dose until the end of the safety follow-up period (60 days after last dose), up to approximately 5 years
measure: Part 1 and Part 2, Arms 2-5: ORR
timeFrame: Up to 1.5 years
measure: Both parts: CR Rate
timeFrame: Up to 1.5 years
measure: Both parts: Duration of Response (DOR)
timeFrame: Up to 1.5 years
measure: Both parts: Progression Free Survival (PFS)
timeFrame: Up to 1.5 years
measure: Part 2: Duration of CR (DoCR)
timeFrame: Up to 1.5 years
measure: Part 2: Time to Response (TTR)
timeFrame: Up to 1.5 years
measure: Part 1 and Part 2 arm 1: Time to Next Anti-lymphoma Therapy (TTNT)
timeFrame: Up to 1.5 years
measure: Both parts: Overall Survival (OS)
timeFrame: Up to 1.5 years
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Aichi Cancer Center Hospital
city: Aichi
country: Japan
facility: NHO Nagoya Medical Center
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Ehime
country: Japan
facility: Matsuyama Red Cross Hospital
city: Fukuoka-shi
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Yamagata
country: Japan
facility: Yamagata University Hospital
Study officials:
References: