Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With R/R B-NHL
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 |
---|---|---|
|
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
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:
|
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:
Drug: rituximab and lenalidomide
28-day cycles.
Other Names:
|
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:
Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
21-day cycles
Other Names:
|
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:
Drug: gemcitabine and oxaliplatin
28-day cycles
Other Names:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
- 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
- Part 2, Arms 2-4: Incidence of DLTs [DLTs are assessed during the first cycle (28 days) in arms 2-4]
- 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
- 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]
- Both parts: AUC from Time 0 to Infinity (AUCinf) [From first dose until treatment discontinuation, expected average of 1 year]
- Both parts: Maximum (peak) plasma concentration (Cmax) [From first dose until treatment discontinuation, expected average of 1 year]
- Both parts: Time to reach Cmax (Tmax) [From first dose until treatment discontinuation, expected average of 1 year]
- Both parts: Pre-dose (trough) concentrations (Cthrough) [From first dose until treatment discontinuation, expected average of 1 year]
- Both parts: Total body clearance of drug from the plasma (CL) [From first dose until treatment discontinuation, expected average of 1 year]
- Both parts: Volume of distribution (Vd) [From first dose until treatment discontinuation, expected average of 1 year]
- Both parts: Elimination half-life (t 1/2) [From first dose until treatment discontinuation, expected average of 1 year]
- Both parts: Incidence of Anti-Drug-Antibodies (ADAs) [From first dose until treatment discontinuation, expected average of 1 year]
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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.
- 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.
- Both parts: Overall Survival (OS) [Approximately 3 years after the last subject's first dose]
Defined as time to death.
Eligibility Criteria
Criteria
Main Inclusion Criteria:
• Must be at least 20 years of age, inclusive
• Japanese subjects
• CD20 positivity at representative tumor biopsy
- 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
- 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.- GCT3013-04 / EPCORE(TM) NHL-3
- JapicCTI no 205408