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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04663347




Registration number
NCT04663347
Ethics application status
Date submitted
27/10/2020
Date registered
11/12/2020

Titles & IDs
Public title
Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)
Scientific title
A Phase 1b/2, Open-Label Trial to Assess the Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Combination With Other Agents in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)
Secondary ID [1] 0 0
2020-000845-15
Secondary ID [2] 0 0
GCT3013-02
Universal Trial Number (UTN)
Trial acronym
EPCORE™ NHL-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Large B-Cell Lymphoma 0 0
Follicular Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
Treatment: Drugs - rituximab and lenalidomide
Treatment: Drugs - rituximab and bendamustine
Treatment: Drugs - rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
Treatment: Drugs - gemcitabine and oxaliplatin
Treatment: Other - Epcoritamab
Treatment: Drugs - rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
Treatment: Drugs - Lenalidomide
Treatment: Drugs - rituximab, ifosfamide, carboplatin, and etoposide phosphate
Treatment: Other - Epcoritamab
Treatment: Other - Epcoritamab
Treatment: Other - Epcoritamab
Treatment: Other - Epcoritamab
Treatment: Other - Epcoritamab
Treatment: Other - Epcoritamab
Treatment: Other - Epcoritamab

Experimental: Arm 1 - Epcoritamab + R-CHOP - In participants with previously untreated DLBCL.

Experimental: Arm 2 - Epcoritamab + R2 - In participants with R/R FL.

Experimental: Arm 3 - Epcoritamab + BR - In participants with previously untreated FL.

Experimental: Arm 4 - Epcoritamab + R-DHAX/C - In participants with R/R DLBCL eligible for ASCT.

Experimental: Arm 5 - Epcoritamab + GemOx - In participants with R/R DLBCL ineligible ASCT.

Experimental: Arm 6 - Epcoritamab + R2 - In participants with previously untreated FL.

Experimental: Arm 7 - Epcoritamab maintenance - In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L.

Experimental: Arm 8 - Epcoritamab + R mini-CHOP - In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline.

Experimental: Arm 9 - Epcoritamab + Lenalidomide - In participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy.

Experimental: Arm 10 - Epcoritamab + R-ICE - In participants with R/R DLBCL eligible for ASCT.


Treatment: Drugs: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
21-day cycles

Treatment: Drugs: rituximab and lenalidomide
28-day cycles

Treatment: Drugs: rituximab and bendamustine
28-day cycles

Treatment: Drugs: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
21-day cycles

Treatment: Drugs: gemcitabine and oxaliplatin
28-day cycles

Treatment: Other: Epcoritamab
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.

Treatment: Drugs: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
21-day cycles

Treatment: Drugs: Lenalidomide
28-day cycles

Treatment: Drugs: rituximab, ifosfamide, carboplatin, and etoposide phosphate
21-day cycles

Treatment: Other: Epcoritamab
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.

Treatment: Other: Epcoritamab
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until disease progression or unacceptable toxicity.

Treatment: Other: Epcoritamab
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.

Treatment: Other: Epcoritamab
Every week in cycle 1 and then every 8 weeks for a total of 2 years.

Treatment: Other: Epcoritamab
Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.

Treatment: Other: Epcoritamab
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.

Treatment: Other: Epcoritamab
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until transplant or disease progression.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Number of Participants With Dose limiting Toxicities (DLTs)
Timepoint [1] 0 0
During the first cycle (Cycle length= 28 days) in each cohort
Primary outcome [2] 0 0
Part 1 and Part 2 (Arm 7): Number of Participants With Adverse Events (AEs)
Timepoint [2] 0 0
From first dose of trial medication to the maximum of 60 days after last dose of epcoritamab or initiation of subsequent anti-lymphoma therapy.
Primary outcome [3] 0 0
Part 2 (Except Arm 7): Overall Response Rate (ORR)
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Part 1 and 2: Clearance (CL) of Epcoritamab
Timepoint [1] 0 0
Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary outcome [2] 0 0
Part 1 and 2: Volume of Distribution (Vd) of Epcoritamab
Timepoint [2] 0 0
Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary outcome [3] 0 0
Part 1 and 2: Area Under the Concentration-Time Curve (AUC) from Time Zero to Last Quantifiable Dose (AUC0-last) of Epcoritamab
Timepoint [3] 0 0
Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary outcome [4] 0 0
Part 1 and 2: Area Under the Concentration-Time Curve (AUC) from Time Zero to Infinity (AUC0-inf) of Epcoritamab
Timepoint [4] 0 0
Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary outcome [5] 0 0
Part 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) of Epcoritamab
Timepoint [5] 0 0
Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary outcome [6] 0 0
Part 1 and 2: Time to Reach Cmax (Tmax) of Epcoritamab
Timepoint [6] 0 0
Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary outcome [7] 0 0
Part 1 and 2: Terminal Elimination Half-Life (t 1/2) of Epcoritamab
Timepoint [7] 0 0
Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary outcome [8] 0 0
Part 1 and 2: Plasma Trough (Pre-dose) Concentrations (Ctrough) of Epcoritamab
Timepoint [8] 0 0
Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary outcome [9] 0 0
Part 1 and 2: Number of Immune Cell Populations
Timepoint [9] 0 0
Up to 2 years
Secondary outcome [10] 0 0
Part 1 and 2: Percentage of Immune Cell Populations
Timepoint [10] 0 0
Up to 2 years
Secondary outcome [11] 0 0
Part 1 and 2: Change From Baseline in Cytokine Levels up to Cycle 3
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
Part 1 and 2: Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (DNA) Level up to End of Treatment (up to 2 Years)
Timepoint [12] 0 0
Up to 2 years
Secondary outcome [13] 0 0
Part 1 and 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Epcoritamab
Timepoint [13] 0 0
Up to 3 years
Secondary outcome [14] 0 0
Part 1: ORR
Timepoint [14] 0 0
Up to 3 years
Secondary outcome [15] 0 0
Part 1 and 2: Duration of Response (DOR)
Timepoint [15] 0 0
Up to 3 years
Secondary outcome [16] 0 0
Part 1 and 2: Time to Response (TTR)
Timepoint [16] 0 0
Up to 3 years
Secondary outcome [17] 0 0
Part 1 and 2: Progression Free Survival (PFS)
Timepoint [17] 0 0
Up to 3 years
Secondary outcome [18] 0 0
Part 1 and 2: Overall Survival (OS)
Timepoint [18] 0 0
Up to 3 years
Secondary outcome [19] 0 0
Part 1 and 2: Time to Next Anti-lymphoma Therapy (TTNT)
Timepoint [19] 0 0
Up to 3 years
Secondary outcome [20] 0 0
Part 1 and 2: Percentage of Participants With Minimal Residual Disease (MRD) Negativity
Timepoint [20] 0 0
Up to 3 years
Secondary outcome [21] 0 0
Part 1 and 2: Duration of minimal residual disease (MRD) negativity
Timepoint [21] 0 0
Up to 3 years
Secondary outcome [22] 0 0
Part 2 (Arm 7): Percentage of Participants Who Converted From MRD Positivity to MRD Negativity
Timepoint [22] 0 0
Up to 3 years
Secondary outcome [23] 0 0
Part 2 (Except Arm 7): Percentage of Participants with Complete Response (CR) in Arms 1 to 10
Timepoint [23] 0 0
Up to 3 years
Secondary outcome [24] 0 0
Part 2 (Arm 7): Percentage of Participants With CR
Timepoint [24] 0 0
Week 24, Week 48, and Week 96
Secondary outcome [25] 0 0
Part 1 and 2: Time to Complete Response (TTCR)
Timepoint [25] 0 0
Up to 3 years
Secondary outcome [26] 0 0
Part 1 and 2: Duration of Complete Response (DoCR)
Timepoint [26] 0 0
Up to 3 years

Eligibility
Key inclusion criteria
Key Inclusion Criteria

1. Measurable disease defined as =1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or =1 measurable extra-nodal lesion (long axis >1.0 cm) on computed tomography (CT) or magnetic resonance imaging (MRI)
2. Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
3. Acceptable organ function at screening
4. CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
5. If of childbearing potential subject must practicing a highly effective method of birth control
6. A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control

Arm 1:

* Newly diagnosed DLBCL
* DLBCL, not otherwise specified (NOS)
* "Double-hit" or "triple-hit" DLBCL
* FL Grade 3B

Arm 2: R/R FL

Arm 3: Newly diagnosed, previously untreated FL grade 1-3A

Arm 4:

* Documented R/R DLBCL and eligible for HDT-ASCT
* DLBCL, NOS
* "Double-hit" or "triple-hit" DLBCL
* FL Grade 3B

Arm 5:

* Documented R/R DLBCL and ineligible for HDT-ASCT
* DLBCL, NOS
* "Double-hit" or "triple-hit" DLBCL
* FL Grade 3B

Arm 6: Newly diagnosed, previously untreated FL grade 1-3A

Arm 7:

* FL Grade 1-3A
* If PR or CR per Lugano criteria following first-line or second-line treatment with SOC regimen, and last dose of SOC within 6 months prior to enrollment.

Arm 8:

* Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline
* T-cell/histiocyte rich DLBCL
* "Double-hit" or "triple-hit" DLBCL
* FL Grade 3B

Arm 9:

* R/R FL
* Progressed within 24 months of initiating first-line treatment

Arm 10:

* Documented R/R DLBCL and eligible for HDT-ASCT
* DLBCL, NOS
* "Double-hit" or "triple-hit" DLBCL
* FL Grade 3B

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
2. Any prior treatment with a bispecific antibody targeting CD3 and CD20.
3. Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab
4. Clinically significant cardiovascular disease
5. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
6. CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture
7. Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
8. Known history of seropositivity of human immunodeficiency virus (HIV)
9. Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
10. Neuropathy > grade 1
11. Receiving immunostimulatory agent
12. Prior allogeneic HSCT
13. Current seizure disorder requiring anti-epileptic therapy

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2029
Actual
Sample size
Target
662
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [2] 0 0
Austin Health - Heidelberg
Recruitment hospital [3] 0 0
Linear Clinical Research Limited - Nedlands
Recruitment postcode(s) [1] 0 0
3084 - Clayton
Recruitment postcode(s) [2] 0 0
VIC 3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Belgium
State/province [10] 0 0
Brugge
Country [11] 0 0
Belgium
State/province [11] 0 0
Gent
Country [12] 0 0
Belgium
State/province [12] 0 0
Yvoir
Country [13] 0 0
Czechia
State/province [13] 0 0
Hradec Králové
Country [14] 0 0
Czechia
State/province [14] 0 0
Ostrava - Poruba
Country [15] 0 0
Czechia
State/province [15] 0 0
Prague
Country [16] 0 0
Czechia
State/province [16] 0 0
Praha 2
Country [17] 0 0
Denmark
State/province [17] 0 0
Arhus
Country [18] 0 0
Denmark
State/province [18] 0 0
Copenhagen
Country [19] 0 0
Denmark
State/province [19] 0 0
Odense
Country [20] 0 0
Denmark
State/province [20] 0 0
Vejle
Country [21] 0 0
Finland
State/province [21] 0 0
Helsinki
Country [22] 0 0
Finland
State/province [22] 0 0
Kuopio
Country [23] 0 0
Finland
State/province [23] 0 0
Lahti
Country [24] 0 0
France
State/province [24] 0 0
Bordeaux
Country [25] 0 0
France
State/province [25] 0 0
Dijon
Country [26] 0 0
France
State/province [26] 0 0
Lille
Country [27] 0 0
France
State/province [27] 0 0
Marseille
Country [28] 0 0
France
State/province [28] 0 0
Paris
Country [29] 0 0
France
State/province [29] 0 0
Pierre-Bénite
Country [30] 0 0
Italy
State/province [30] 0 0
Bergamo
Country [31] 0 0
Italy
State/province [31] 0 0
Bologna
Country [32] 0 0
Italy
State/province [32] 0 0
Candiolo
Country [33] 0 0
Italy
State/province [33] 0 0
Meldola
Country [34] 0 0
Italy
State/province [34] 0 0
Milan
Country [35] 0 0
Italy
State/province [35] 0 0
Pavia
Country [36] 0 0
Italy
State/province [36] 0 0
Reggio Emilia
Country [37] 0 0
Netherlands
State/province [37] 0 0
Amsterdam
Country [38] 0 0
Netherlands
State/province [38] 0 0
Groningen
Country [39] 0 0
Netherlands
State/province [39] 0 0
Leiden
Country [40] 0 0
Netherlands
State/province [40] 0 0
Maastricht
Country [41] 0 0
Netherlands
State/province [41] 0 0
Rotterdam
Country [42] 0 0
Netherlands
State/province [42] 0 0
Utrecht
Country [43] 0 0
Norway
State/province [43] 0 0
Oslo
Country [44] 0 0
Spain
State/province [44] 0 0
Barcelona
Country [45] 0 0
Spain
State/province [45] 0 0
Madrid
Country [46] 0 0
Spain
State/province [46] 0 0
Salamanca
Country [47] 0 0
Sweden
State/province [47] 0 0
Borås
Country [48] 0 0
Sweden
State/province [48] 0 0
Göteborg
Country [49] 0 0
Sweden
State/province [49] 0 0
Lund
Country [50] 0 0
Sweden
State/province [50] 0 0
Solna
Country [51] 0 0
Sweden
State/province [51] 0 0
Umeå
Country [52] 0 0
Sweden
State/province [52] 0 0
Uppsala
Country [53] 0 0
United Kingdom
State/province [53] 0 0
London
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Manchester
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Newcastle Upon Tyne
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genmab
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
AbbVie
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Genmab A/S Trial Information
Address 0 0
Country 0 0
Phone 0 0
+45 70202728
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04663347