Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With R/R B-NHL
- Conditions
- Diffuse Large B Cell LymphomaPrimary Mediastinal Large B Cell LymphomaHigh-grade B-cell LymphomaFollicular LymphomaSmall Lymphocytic LymphomaMarginal Zone Lymphoma
- Interventions
- Registration Number
- NCT04542824
- Lead Sponsor
- Genmab
- 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.
- 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 102
• 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
• 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description arm 4: epcoritamab + gemcitabine + oxaliplatin gemcitabine and oxaliplatin In subjects with relapsed/refractory DLBCL arm 2: epcoritamab + rituximab + lenalidomide rituximab and lenalidomide In subjects with relapsed/refractory FL arm 1: epcoritamab epcoritamab (monotherapy) In subjects with DLBCL/FL arm 3: epcoritamab + rituximab + cyclophosphamide+ doxorubicin+ vincristine + prednisone epcoritamab In subjects with previously untreated DLBCL arm 2: epcoritamab + rituximab + lenalidomide epcoritamab In subjects with relapsed/refractory FL arm 3: epcoritamab + rituximab + cyclophosphamide+ doxorubicin+ vincristine + prednisone rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone In subjects with previously untreated DLBCL arm 4: epcoritamab + gemcitabine + oxaliplatin epcoritamab In subjects with relapsed/refractory DLBCL arm 5: epcoritamab maintenance epcoritamab (maintenance) In subjects with FL in complete response (CR) or in partial response (PR) following first line or second line SOC treatment
- Primary Outcome Measures
Name Time Method 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 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 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
Name Time Method Both parts: Maximum (peak) plasma concentration (Cmax) 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 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 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.
Both parts: Overall Survival (OS) Approximately 3 years after the last subject's first dose Defined as time to death.
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: 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 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.
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: 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
Trial Locations
- Locations (14)
Kagoshima University Hospital
🇯🇵Kagoshima-shi, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka-shi, Japan
National Cancer Center Hospital
🇯🇵Chuo Ku, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima-shi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Japan
Kyoto University Hospital
🇯🇵Kyoto-shi, Japan
Cancer Institute Hospital of JFCR
🇯🇵Koto-Ku, Japan
Matsuyama Red Cross Hospital
🇯🇵Matsuyama-shi, Japan
Aichi Cancer Center Hospital
🇯🇵Nagoya-shi, Japan
NHO Nagoya Medical Center
🇯🇵Nagoya-shi, Japan
Tokyo Medical University Hospital
🇯🇵Shinjuku-Ku, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Osaka University Hospital
🇯🇵Suita-shi, Japan
Yamagata University Hospital
🇯🇵Yamagata-shi, Japan