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

Follicular Lymphoma Clinical Trial

— EPCORE™ NHL-3  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04542824
• Other study ID #: GCT3013-04
• Secondary ID: JapicCTI no 2054
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 20, 2020
• Est. completion date: December 30, 2024

Study information

• Verified date: May 2024
• Source: Genmab
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 102
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Follicular Lymphoma
• High-grade B-cell Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Marginal Zone Lymphoma
• Primary Mediastinal Large B Cell Lymphoma
• Small Lymphocytic Lymphoma

Intervention

Biological:
• epcoritamab (monotherapy)
Epcoritamab will be administered subcutaneously in cycles of 4 weeks (i.e. 28 days)
• epcoritamab
Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.

Drug:
• rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
21-day cycles
• gemcitabine and oxaliplatin
28-day cycles

Biological:
• epcoritamab (maintenance)
28-day cycle for Cycle 1 and then 56-day cycle from Cycle 2 through 13

Drug:
• rituximab and lenalidomide
28-day cycles.

Locations

Country	Name	City	State
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

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	AbbVie

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Incidence and severity of Adverse Events (AEs)	Treatment emergent AEs.	From first dose until the end of the safety follow-up period (60 days after last dose)
Primary	Part 1: Incidence of Dose limiting toxicities (DLTs)	To determine the RP2D and the MTD, if reached.	DLTs are assessed during the first cycle (28 days) in each cohort
Primary	Part 2, Arm 1: Objective response rate (ORR)	Antitumor activity as measured by the ORR according to Lugano classification	From 6 weeks after enrollment until treatment discontinuation, assessed up to 3 years
Primary	Part 2, Arms 2-4: Incidence of DLTs		DLTs are assessed during the first cycle (28 days) in arms 2-4
Primary	Part 2, Arms 2-5: Incidence and severity of AEs	Treatment emergent AEs (TEAEs)	From first dose until the end of the safety follow-up period (60 days after last dose)
Secondary	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
Secondary	Both parts: AUC from Time 0 to Infinity (AUCinf)		From first dose until treatment discontinuation, expected average of 1 year
Secondary	Both parts: Maximum (peak) plasma concentration (Cmax)		From first dose until treatment discontinuation, expected average of 1 year
Secondary	Both parts: Time to reach Cmax (Tmax)		From first dose until treatment discontinuation, expected average of 1 year
Secondary	Both parts: Pre-dose (trough) concentrations (Cthrough)		From first dose until treatment discontinuation, expected average of 1 year
Secondary	Both parts: Total body clearance of drug from the plasma (CL)		From first dose until treatment discontinuation, expected average of 1 year
Secondary	Both parts: Volume of distribution (Vd)		From first dose until treatment discontinuation, expected average of 1 year
Secondary	Both parts: Elimination half-life (t 1/2)		From first dose until treatment discontinuation, expected average of 1 year
Secondary	Both parts: Incidence of Anti-Drug-Antibodies (ADAs)		From first dose until treatment discontinuation, expected average of 1 year
Secondary	Part 1 and Part 2, Arm1: Number of participants with clinically significant shifts from baseline in clinical laboratory parameters	Clinical laboratory parameters assessed: biochemistry, hematology	From first dose until treatment discontinuation, expected average of 1 year
Secondary	Part 2, Arm1: Incidence and severity of AEs	TEAEs as assessed by CTCAE V5.0.	From first dose until the end of the safety follow-up period (60 days after last dose)
Secondary	Part 1 and Part 2, arms 2-5: ORR	Defined as proportion of participants who have a PR or CR following treatment with epcoritamab. Determined by the Lugano response criteria.	Approximately 3 years after the last subject's first dose
Secondary	Both parts: CR rate	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.	Approximately 3 years after the last subject's first dose
Secondary	Both parts: Duration of Response (DOR)	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.	Approximately 3 years after the last subject's first dose
Secondary	Both parts: Progression Free Survival (PFS)	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.	Approximately 3 years after the last subject's first dose
Secondary	Part 2: Duration of CR (DoCR)	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	Approximately 3 years after the last subject's first dose
Secondary	Part 2: Time to Response (TTR)	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.	Approximately 3 years after the last subject's first dose
Secondary	Part 1 and Part 2 arm 1: Time to next anti-lymphoma therapy (TTNT)	Calculated as time to date of initiation of new anti-lymphoma therapy.	Approximately 3 years after the last subject's first dose
Secondary	Both parts: Overall Survival (OS)	Defined as time to death.	Approximately 3 years after the last subject's first dose