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Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)
The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, when treating subjects with B-cell non-Hodgkin Lymphoma (B-NHL). The aim of the first part of the trial is to identify the most appropriate dose of epcoritamab, and the aim of the second part of the trial is to assess the selected epcoritamab dose in a larger group of participants with B-NHL. All participants in this trial will receive either epcoritamab alone, or epcoritamab combined with another standard treatment regimen, with a total of 10 different treatment arms being studied.
Trial details include: * The total trial duration will be up to 6 years. * The treatment duration for each participant depends upon which arm of treatment they are assigned to receive, but will be no more than 3 years. * The visit frequency for each participant depends upon which arm of treatment they are assigned to receive, but will be weekly to start for all participants, then will decrease to either: every 2 weeks, or every 3 weeks, or every 4 weeks, or every 8 weeks.
* All participants will receive active drug; no one will be given placebo. Participants who receive treatment with epcoritamab will have it injected right under the skin. Participants will receive a different regimen of epcoritamab depending upon which arm of treatment they are assigned.
Participants who receive standard treatments will have IV infusions and/or oral administration of those treatments. Participants will receive a different standard treatment regimen depending upon which arm of treatment they are assigned. Arm 9 (follicular lymphoma (FL)) is still open for enrolment of new patients, while the other arms have closed their recruitment.
Study details:
A phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab in combination with other standard of care (SOC) agents in participants with B-NHL. All participants in the trial will receive epcoritamab, as monotherapy or in combination. The following regimens will be investigated:.
* Arm 1: epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with previously untreated diffuse large B-cell lymphoma (DLBCL). * Arm 2: epcoritamab + rituximab and lenalidomide (R2) in participants with relapsed/refractory (R/R) FL. * Arm 3: epcoritamab + rituximab and bendamustine (BR) in participants with previously untreated FL.
* Arm 4: epcoritamab + rituximab, cytarabine, dexamethasone, and oxaliplatin/ carboplatin (R-DHAX/C) in participants with R/R DLBCL eligible for autologous stem cell transplant (ASCT). * Arm 5: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants with R/R DLBCL ineligible for ASCT due to age, performance status (PS), or comorbidity. * Arm 6: epcoritamab + R2 in participants with previously untreated FL.
* Arm 7: epcoritamab maintenance in participants with FL who achieve a complete response (CR) or a partial response (PR) with SOC treatment. * Arm 8: epcoritamab + reduced dose of R-CHOP (R mini-CHOP) in participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline. * Arm 9: epcoritamab + lenalidomide for second-line treatment in participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy.
* Arm 10: epcoritamab + rituximab, ifosfamide, carboplatin, and etoposide phosphate (R-ICE) in participants with R/R DLBCL eligible for ASCT. The trial consists of two parts: Part 1 ('Dose Escalation') and Part 2 ('Dose Expansion'). The primary objective of Part 1 is safety, and it includes Arm 1-5 and Arm 10.
Part 2 includes all 10 arms (Arm 1-10) and the primary goal of all arms, except Arm 7, is preliminary efficacy. For Arm 7, the primary goal is safety. Patients in Arm 1-5 and Arm 10 can only participate in either Part 1 or Part 2.
Dose Limiting Toxicities (DLTs) will be assessed in Part 1 and for a selected number of patients in Arm 8 during a 28-day period ('safety-run phase'). The arms are conducted in parallel.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2020-11-03
Primary completion: 2029-03-31
Study completion finish: 2029-03-31
Study type
TREATMENT
Phase
PHASE1
PHASE2
Trial ID
NCT04663347
Intervention or treatment
DRUG: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
DRUG: rituximab and lenalidomide
DRUG: rituximab and bendamustine
DRUG: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
DRUG: gemcitabine and oxaliplatin
BIOLOGICAL: Epcoritamab
DRUG: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
DRUG: Lenalidomide
DRUG: rituximab, ifosfamide, carboplatin, and etoposide phosphate
BIOLOGICAL: Epcoritamab
BIOLOGICAL: Epcoritamab
BIOLOGICAL: Epcoritamab
BIOLOGICAL: Epcoritamab
BIOLOGICAL: Epcoritamab
BIOLOGICAL: Epcoritamab
BIOLOGICAL: Epcoritamab
Conditions
- • Diffuse Large B-Cell Lymphoma
- • Follicular Lymphoma
Find a site
Closest Location:
Linear Clinical Research Limited
Research sites nearby
Select from list below to view details:
Linear Clinical Research Limited
Nedlands, Not Specified, Australia
Monash Medical Centre
Clayton, Victoria, Australia
Austin Health
Heidelberg, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Arm 1 - Epcoritamab + R-CHOP
| DRUG: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
|
EXPERIMENTAL: Arm 2 - Epcoritamab + R2
| DRUG: rituximab and lenalidomide
|
EXPERIMENTAL: Arm 3 - Epcoritamab + BR
| DRUG: rituximab and bendamustine
|
EXPERIMENTAL: Arm 4 - Epcoritamab + R-DHAX/C
| DRUG: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
|
EXPERIMENTAL: Arm 5 - Epcoritamab + GemOx
| DRUG: gemcitabine and oxaliplatin
|
EXPERIMENTAL: Arm 6 - Epcoritamab + R2
| DRUG: rituximab and lenalidomide
|
EXPERIMENTAL: Arm 7 - Epcoritamab maintenance
| BIOLOGICAL: Epcoritamab
|
EXPERIMENTAL: Arm 8 - Epcoritamab + R mini-CHOP
| DRUG: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
|
EXPERIMENTAL: Arm 9 - Epcoritamab + Lenalidomide
| DRUG: Lenalidomide
|
EXPERIMENTAL: Arm 10 - Epcoritamab + R-ICE
| DRUG: rituximab, ifosfamide, carboplatin, and etoposide phosphate
|
What is the study measuring?
Primary outcome
| Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
|---|---|---|
| Part 1: Number of Participants With Dose limiting Toxicities (DLTs) | DLT events are defined as clinically significant adverse events (AEs) or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications as assessed per Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0. | During the first cycle (Cycle length= 28 days) in each cohort |
| Part 1 and Part 2 (Arm 7): Number of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign. (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From first dose of trial medication to the maximum of 60 days after last dose of epcoritamab or initiation of subsequent anti-lymphoma therapy. |
| Part 2 (Except Arm 7): Overall Response Rate (ORR) | ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria. | Up to 3 years |
Secondary outcome
| Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
|---|---|---|
| Part 1 and 2: Clearance (CL) of Epcoritamab | Not Specified | Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) |
| Part 1 and 2: Volume of Distribution (Vd) of Epcoritamab | Not Specified | Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) |
| Part 1 and 2: Area Under the Concentration-Time Curve (AUC) from Time Zero to Last Quantifiable Dose (AUC0-last) of Epcoritamab | Not Specified | Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) |
| Part 1 and 2: Area Under the Concentration-Time Curve (AUC) from Time Zero to Infinity (AUC0-inf) of Epcoritamab | Not Specified | Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) |
| Part 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) of Epcoritamab | Not Specified | Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) |
| Part 1 and 2: Time to Reach Cmax (Tmax) of Epcoritamab | Not Specified | Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) |
| Part 1 and 2: Terminal Elimination Half-Life (t 1/2) of Epcoritamab | Not Specified | Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) |
| Part 1 and 2: Plasma Trough (Pre-dose) Concentrations (Ctrough) of Epcoritamab | Not Specified | Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) |
| Part 1 and 2: Number of Immune Cell Populations | Immune cell populations in peripheral blood and tumor biopsies will be assessed. | Up to 2 years |
| Part 1 and 2: Percentage of Immune Cell Populations | Immune cell populations in peripheral blood and tumor biopsies will be assessed. | Up to 2 years |
| Part 1 and 2: Change From Baseline in Cytokine Levels up to Cycle 3 | Change in cytokine levels in peripheral blood samples will be assessed. | Up to Cycle 3 (cycle length = 21 days for Arms 1, 4, 8 and 10; cycle length = 28 days for Arms 2, 3, 5, 6 and 9; cycle length = 28 days (Cycle 1) and 56 days (Cycles 2, 3) for Arm 7) |
| Part 1 and 2: Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (DNA) Level up to End of Treatment (up to 2 Years) | Change in circulating tumor DNA levels will be assessed. | Up to 2 years |
| Part 1 and 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Epcoritamab | Not Specified | Up to 3 years |
| Part 1: ORR | ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria. | Up to 3 years |
| Part 1 and 2: Duration of Response (DOR) | DOR: the time from the first documentation of objective tumor response (CR or PR) to the date of first PD or death based on Lugano criteria. | Up to 3 years |
| Part 1 and 2: Time to Response (TTR) | TTR is defined as the time from Day 1 of Cycle 1 to first documentation of objective tumor response (CR or PR). | Up to 3 years |
| Part 1 and 2: Progression Free Survival (PFS) | PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause based on Lugano criteria. | Up to 3 years |
| Part 1 and 2: Overall Survival (OS) | OS is defined as the time from the date of first dose, to the date of death due to any cause. | Up to 3 years |
| Part 1 and 2: Time to Next Anti-lymphoma Therapy (TTNT) | TTNT is defined as the time from Day 1 of Cycle 1 to first documented administration of subsequent anti-lymphoma therapy. | Up to 3 years |
| Part 1 and 2: Percentage of Participants With Minimal Residual Disease (MRD) Negativity | It is defined as the percentage of participants with at least 1 MRD negative result. | Up to 3 years |
| Part 1 and 2: Duration of minimal residual disease (MRD) negativity | Not Specified | Up to 3 years |
| Part 2 (Arm 7): Percentage of Participants Who Converted From MRD Positivity to MRD Negativity | Not Specified | Up to 3 years |
| Part 2 (Except Arm 7): Percentage of Participants with Complete Response (CR) in Arms 1 to 10 | Not Specified | Up to 3 years |
| Part 2 (Arm 7): Percentage of Participants With CR | It is defined as the percentage of participants who remain in complete remission or converting to complete remission after first trial drug administration. | Week 24, Week 48, and Week 96 |
| Part 1 and 2: Time to Complete Response (TTCR) | TTCR is defined as the time from first trial drug administration to the date of first documented complete response post-treatment. | Up to 3 years |
| Part 1 and 2: Duration of Complete Response (DoCR) | DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs first based on Lugano criteria. | Up to 3 years |
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