First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma
- Conditions
- Marginal Zone Lymphoma (MZL)Indolent B-cell Non-Hodgkin Lymphoma (iNHL)Aggressive B-cell Non-Hodgkin Lymphoma (aNHL)DLBCLHigh-grade B-cell Lymphoma (HGBCL)Primary Mediastinal Large B-cell Lymphoma (PMBCL)FLMCLSmall Lymphocytic Lymphoma (SLL)
- Interventions
- Registration Number
- NCT03625037
- Lead Sponsor
- Genmab
- Brief Summary
The purpose of this trial is to measure the following in participants with relapsed and/or refractory B-cell lymphoma who receive epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20):
* The dose schedule for epcoritamab
* The side effects seen with epcoritamab
* What the body does with epcoritamab once it is administered
* What epcoritamab does to the body once it is administered
* How well epcoritamab works against relapsed and/or refractory B-cell lymphoma
The trial consists of 3 parts:
* a dose-escalation part (Phase 1, first-in-human \[FIH\])
* an expansion part (Phase 2a)
* a dose-optimization part (OPT) (Phase 2a)
The trial time for each participant depends on which trial part the participant enters:
* For the dose-escalation part, each participant will be in the trial for approximately 1 year, which is made up of 21 days of screening, 6 months of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant).
* For the expansion and dose-OPT parts, each participant will be in the trial for approximately 1.5 years, which is made up of 21 days of screening, 1 year of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant).
Participation in the study will require visits to the sites. During the first month, participants must visit every day or every few days, depending on which trial part the participant enters. After that, participants must visit weekly, every other week, once a month, and once every 2 months, as trial participation ends.
All participants will receive active drug, and no participants will be given placebo.
- Detailed Description
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 participants with relapsed or refractory B-cell lymphoma.
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.
The dose-OPT part will evaluate alternative priming and intermediate dose regimens of epcoritamab in participants with:
* Diffuse large B-cell lymphoma (DLBCL)
* Follicular lymphoma (FL)
* Mantle cell lymphoma (MCL)
All participants will receive epcoritamab at the RP2D.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 666
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Epcoritamab Epcoritamab Epcoritamab will be administered by subcutaneous injections in cycles of 28 days.
- Primary Outcome Measures
Name Time Method Dose-Escalation: Dose Limiting Toxicity (DLT) During the first cycle (28 days) To determine the MTD and/or RP2D to be studied in the Expansion part. DLT will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Dose-Escalation: Number of Participants with Adverse Events (AEs) From first dose until the end of the safety follow-up period (Up to 1 year) An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Expansion: Overall Response Rate (ORR) Up to 1.5 years ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.
Dose-OPT DLBCL, FL and MCL: Percentage of Participants with =>Grade 2 Cytokine Release Syndrome (CRS) Events and All Grade CRS Events From first dose until 7 days after second full dose (Day 28 for DLBCL; Day 35 for FL; Day 28-35 for MCL) CRS will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
- Secondary Outcome Measures
Name Time Method Expansion: Trough Concentration of Epcoritamab Up to 1.5 years Dose-OPT DLBCL and FL: Duration of CR (DoCR) Up to 1.5 years DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs earlier assessed by investigator.
Dose-OPT DLBCL and FL: Progression-Free Survival (PFS) Up to 1.5 years PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause, whichever occurs earlier assessed by investigator.
Expansion and Dose-OPT MCL: DoCR Up to 1.5 years DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs earlier based on LYRIC.
Expansion and Dose-OPT MCL: ORR Up to 1.5 years ORR is defined as the percentage of participants achieving CR or PR based on LYRIC.
All Parts: Total Body Clearance of Epcoritamab from the Plasma (CL) Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days), Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part: Up to 1.5 years All Parts: Area under Curve (AUC) of Epcoritamab Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days), Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part: Up to 1.5 years All Parts: Maximum (peak) Plasma Concentration (Cmax) of Epcoritamab Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days), Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part: Up to 1.5 years All Parts: Time to Reach Cmax of Epcoritamab Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days), Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part: Up to 1.5 years All Parts: Half Life of Epcoritamab (t1/2) Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days), Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part: Up to 1.5 years All Parts: Number of Participants with Anti-drug Antibody (ADA) Up to 7 years and 6 months Plasma samples will be screened for antibodies binding to epcoritamab, and for confirmed positive samples, the titer against the two specific arms of epcoritamab will be reported.
All Parts: Time to Next Anti-lymphoma Therapy (TTNT) Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part (DLBCL, FL and MCL): Up to 1.5 years TTNT is defined as the time from Day 1 of Cycle 1 to first recorded administration of subsequent anti-lymphoma therapy or death due to any cause, whichever occurs earlier.
All Parts: Overall survival (OS) Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part DLBCL, FL and MCL: Up to 1.5 years OS is defined as the time from Day 1 of Cycle 1 to death.
Dose-Escalation: Number of Participants with Anti-lymphoma Activity of Epcoritamab Up to 1 year Anti-lymphoma activity will be evaluated as number of participants with resolution of constitutional symptoms, reduction in tumor size, objective, and best response (ORR, CR and PR).
Dose-Escalation: Duration of Response (DOR) Up to 1 year DOR is defined as the time from the first documentation of response (CR or PR) to the date of progressive disease (PD) or death, whichever occurs earlier as assessed by the investigator.
Expansion: DOR Up to 1.5 years DOR is defined as the time from the first documentation of response (CR or PR) to the date of PD or death, whichever occurs earlier based on Lugano criteria.
Expansion Part: Changes in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Up to 1.5 year Change from baseline in health-related quality of life over time and in relation to treatment will be evaluated using FACT-Lym scale.
Dose-OPT DLBCL and FL: Percentage of Participants with >=Grade 2 CRS Events and All Grade CRS Events Following First Full Dose Up to 1.5 years CRS will be graded based on ASTCT criteria.
Dose-OPT DLBCL and FL: Percentage of Participants with >=Grade 2 CRS Events and All Grade CRS Events Overall Up to 1.5 years CRS will be graded based on ASTCT criteria.
Dose-OPT DLBCL and FL: ORR Up to 1.5 years ORR is defined as the percentage of participants achieving CR or PR assessed by investigator.
Dose-OPT DLBCL and FL: CR Rate Up to 1.5 years CR rate is defined as the percentage of participants with CR assessed by investigator.
Dose-OPT DLBCL and FL: DLT During the first cycle (28 days) in each Dose-OPT Part (DLBCL, FL and MCL) To determine the MTD and/or RP2D to be studied in the expansion part. DLT will be graded according to NCI-CTCAE version 5.0.
Dose-OPT DLBCL, FL and MCL: DOR Up to 1.5 years DOR is defined as the time from the first documentation of response (CR or PR) to the date of PD or death, whichever occurs earlier based on Lugano criteria assessed by investigator.
Dose-Escalation and Dose-OPT DLBCL, FL and MCL: Pre-dose Values of Epcoritamab Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days), up to approximately 1.5 years Dose-Escalation, Expansion Part and Dose-OPT MCL: PFS Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part (MCL): 1.5 years PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause, whichever occurs earlier based on Lugano criteria.
Expansion and Dose-OPT MCL: CR Rate Up to 1.5 years CR rate is defined as the percentage of participants with CR based on LYRIC.
Expansion: Time to Response (TTR) Up to 1.5 years TTR is defined as the time from Day 1 of Cycle 1 to first documentation of objective tumor response (PR or better) earlier based on Lugano criteria.
Expansion and Dose-OPT MCL: PFS Up to 1.5 years PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause, whichever occurs earlier based on LYRIC.
Expansion and Dose-OPT MCL: DOR Up to 1.5 years DOR is defined as the time from the first documentation of response (CR or PR) to the date of PD or death, whichever occurs earlier based on LYRIC.
Expansion and Dose-OPT: TTR Up to 1.5 years TTR is defined as the time from Day 1 of Cycle 1 to first documentation of objective tumor response (PR or better) earlier based on LYRIC.
Expansion and Dose-OPT DLBCL, FL and MCL: Number of Participants with AEs Up to 7 years and 6 months An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Expansion and Dose-OPT DLBCL, FL and MCL: Rate of Minimal Residual Disease (MRD) Negativity Up to 1.5 years MRD is defined as percentage of participants with at least 1 MRD negative result.
All Parts: Number of Participants with CRS Events Up to Day 1 of Cycle 12 (Cycle length=28 days) CRS will be graded based on ASTCT criteria.
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Trial Locations
- Locations (85)
Arizona Mayo Clinic
🇺🇸Phoenix, Arizona, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
University of Iowa Hospital and Clinics
🇺🇸Iowa City, Iowa, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Hackensack Meridian Health
🇺🇸Hackensack, New Jersey, United States
Scroll for more (75 remaining)Arizona Mayo Clinic🇺🇸Phoenix, Arizona, United States