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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04623541




Registration number
NCT04623541
Ethics application status
Date submitted
27/10/2020
Date registered
10/11/2020

Titles & IDs
Public title
Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
Scientific title
A Phase 1b/2, Open-Label, Safety and Efficacy Study of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome
Secondary ID [1] 0 0
2020-000848-57
Secondary ID [2] 0 0
GCT3013-03
Universal Trial Number (UTN)
Trial acronym
EPCORE™ CLL-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 0 0
Richter's Syndrome 0 0
Treatment-naïve High Risk Chronic Lymphocytic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Other - Epcoritamab
Treatment: Other - Epcoritamab
Treatment: Drugs - rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
Treatment: Drugs - Venetoclax
Treatment: Other - Epcoritamab
Treatment: Drugs - Lenalidomide
Treatment: Other - Epcoritamab
Treatment: Drugs - Pirtobrutinib
Treatment: Other - Epcoritamab

Experimental: Epcoritamab in R/R CLL/SLL - In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase.

Experimental: Epcoritamab in RS - Only in expansion phase.

Experimental: Epcoritamab + Venetoclax in R/R CLL/SLL - In both study phases. Participants in the expansion phase will be treated at the RP2D defined in the dose-escalation phase.

Experimental: Epcoritamab + Lenalidomide in RS - Only in expansion phase.

Experimental: Epcoritamab + R-CHOP in RS - Only in expansion phase.

Experimental: Epcoritamab + Pirtobrutinib in R/R CLL, TN HR CLL and SLL - Safety run-in and expansion phases.

Experimental: Fixed Duration Epcoritamab in R/R CLL/SLL - Only in expansion phase.


Treatment: Other: Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days, (except Cycle 1 for high-dose cohorts = 35 days).

Treatment: Other: Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 21 days and 28 days.

Treatment: Drugs: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
R-CHOP will be administered intravenously (prednisone may be administered orally) in cycles of 21 days.

Treatment: Drugs: Venetoclax
Venetoclax tablets will be administered orally once daily during the 5-week ramp up period in cycles of 28 or 35 days each.

Treatment: Other: Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days.

Treatment: Drugs: Lenalidomide
Lenalidomide capsules will be administered once daily for 21 days in each cycle of 28 days.

Treatment: Other: Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days.

Treatment: Drugs: Pirtobrutinib
Pirtobrutinib tablets will be administered in cycles of 28 days.

Treatment: Other: Epcoritamab
Epcoritamab will be administered subcutaneously in cycles of 28 days.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Escalation Phase and Safety Run-in (R/R CLL arm): Number of Participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
During the first cycle for low dose cohorts (Cycle length = 28 days) and for high dose cohorts (Cycle length = 35 days)
Primary outcome [2] 0 0
Dose Escalation Phase and Safety Run-in: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [2] 0 0
Up to 5 years
Primary outcome [3] 0 0
Dose Escalation Phase: Number of Participants with Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and Clinical Tumor Lysis Syndrome (CTLS)
Timepoint [3] 0 0
Up to 5 years
Primary outcome [4] 0 0
Expansion Phase: Overall Response Rate (ORR)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Expansion Phase: Number of Participants with TEAEs and SAEs
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Dose Escalation Phase and Safety Run-in: ORR (for R/R CLL Participants)
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Both Phases and Safety Run-in: Duration of Response (DOR)
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Both Phases and Safety Run-in: Number of Participants with CR/CRi
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Both Phases and Safety Run-in: Time to Response (TTR)
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Both Phases and Safety Run-in: Progression Free Survival (PFS)
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Both Phases and Safety Run-in: Overall Survival (OS)
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
Both Phase and Safety Run-in: Time to Next Systemic Anti-cancer Therapy (TTNT)
Timepoint [8] 0 0
Up to 5 years
Secondary outcome [9] 0 0
Both Phases and Safety Run-in: Area Under the Concentration-time Curve (AUC) in Epcoritamab
Timepoint [9] 0 0
Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years
Secondary outcome [10] 0 0
Both Phases and Safety Run-in: Maximum (Peak) Plasma Concentration (Cmax) in Epcoritamab
Timepoint [10] 0 0
Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years
Secondary outcome [11] 0 0
Both Phases: Pre-dose (Trough) Concentrations (Cthrough) in Epcoritamab
Timepoint [11] 0 0
Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years
Secondary outcome [12] 0 0
Both Phases and Safety Run-in: Time to Reach Cmax (Tmax) in Epcoritamab
Timepoint [12] 0 0
Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years
Secondary outcome [13] 0 0
Both Phases and Safety Run-in: Elimination Half-life (T1/2) in Epcoritamab
Timepoint [13] 0 0
Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years
Secondary outcome [14] 0 0
Both Phases and Safety Run-in: Total Body Clearance of Drug From Plasma (CL) in Epcoritamab
Timepoint [14] 0 0
Predose and post dose at multiple timepoints at end of each cycle for low dose and high dose cohorts (Cycle length = 28 days, except Cycle 1 for high dose cohorts = 35 Days), up to 5 years
Secondary outcome [15] 0 0
Both Phases: Lymphoid Cells for Immunophenotyping
Timepoint [15] 0 0
Up to 5 years
Secondary outcome [16] 0 0
Expansion Phase: Number of Participants with CRS, ICANS and CTLS
Timepoint [16] 0 0
Up to 5 years
Secondary outcome [17] 0 0
Expansion Phase and Safety Run-in : Percentage of Participants with Minimal Residual Disease (MRD) Negativity
Timepoint [17] 0 0
Up to 5 years
Secondary outcome [18] 0 0
Both Phases and Safety Run-in: Number of Participants with Anti-drug Antibodies (ADA) to Epcoritamab
Timepoint [18] 0 0
Up to 5 years
Secondary outcome [19] 0 0
Expansion Phase: Number of Participants with PR
Timepoint [19] 0 0
Up to 5 years
Secondary outcome [20] 0 0
Both Phases and Safety Run-in: Duration of MRD Negativity
Timepoint [20] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
Key Inclusion Criteria

1. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
2. Evidence of CD20 positivity in a sample representative of the disease at Screening.
3. Acceptable hematology parameters and organ function based on baseline bloodwork.
4. Life expectancy >3 months on standard of care (SOC) for CLL, >3 months for RS.
5. For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
6. For R/R CLL monotherapy arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor or at least 1 prior line of systemic antineoplastic therapy, including treatment with (or intolerance of) a covalent BTK inhibitor (cBTKi) and a B-cell lymphoma 2 (BCL-2) inhibitor.
7. For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
8. For all RS arms - Must have measurable disease by fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) or magnetic resonance imaging (MRI) scan.
9. For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
10. For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
11. For RS - lenalidomide combination therapy arm

* Deemed as ineligible for chemoimmunotherapy at the investigator's discretion, or participant who refuses to receive intensive chemotherapy.
* Eligible for treatment with lenalidomide.
* Must be willing to use contraception and adhere to the Lenalidomide Pregnancy Risk Minimization Plan
* A woman must agree not to breastfeed a child during treatment and for at least 28 days after discontinuation from study.
12. For RS - R-CHOP combination Therapy Arm -

* Eligible for treatment with R-CHOP.
* Females of childbearing potential must use highly effective contraceptive measures while taking R-CHOP and for 12 months after stopping treatment.
* A woman must agree not to breastfeed a child during treatment or until 12 months after last treatment.
13. For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy.

* Presence of measurable disease.
* Must take prophylaxis for tumor lysis syndrome (TLS).
14. For R/R CLL pirtobrutinib combination Therapy arm:

* Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
* Presence of measurable disease.
* Previous treatment with at least one and a maximum 3 prior lines of therapy including a cBTKi.
* Diagnosis of CLL/SLL that met published iwCLL criteria.
15. Participants with TN HR CLL - Pirtobrutinib Combination Therapy Expansion:

* Diagnosis of CLL/SLL that met published iwCLL criteria 2018.
* Must have active CLL/SLL disease that needs treatment per iwCLL
* Must take prophylaxis for TLS based on their TLS risk evaluation upon initiation of trial drug.
* Must have one or more high-risk features.
* Presence of measurable disease.

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. Received prior treatment with a CD3×CD20 bispecific antibody.
2. Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
3. Received chimeric antigen receptor (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of trial drug.
4. Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
5. Received vaccination with live vaccines within 28 days.
6. Clinically significant cardiac disease.
7. Known current malignancy other than inclusion diagnosis.
8. Has had major surgery within 4 weeks.
9. Known history of human immunodeficiency virus (HIV).
10. For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
11. For R/R CLL - Venetoclax Combination Therapy arm: received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial or has progressed on venetoclax treatment.
12. For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
13. RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS.
14. R/R CLL - Pirtobrutinib Combination Therapy Arm - Prior exposure to a non-covalent (reversible) BTK inhibitor or a BTK degrader.
15. Pirtobrutinib Combination Therapy Expansion Arms:

* History of bleeding disorders or participants requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist
* Require continuous treatment with or have received strong cytochrome P450 (CYP) 3A inhibitors or strong/moderate CYP3A inducers within 4 to 5 half-lives or 14 days prior to the first dose of pirtobrutinib.

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
25/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2029
Actual
Sample size
Target
424
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St. George Hospital - Kogarah
Recruitment hospital [2] 0 0
Barwon Health - Geelong
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Alfred Health - Melbourne
Recruitment postcode(s) [1] 0 0
- Kogarah
Recruitment postcode(s) [2] 0 0
- Geelong
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
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
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Belgium
State/province [12] 0 0
Bruges
Country [13] 0 0
Belgium
State/province [13] 0 0
Gent
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Czechia
State/province [15] 0 0
Nové Mesto
Country [16] 0 0
Czechia
State/province [16] 0 0
Nový Hradec Králové
Country [17] 0 0
Czechia
State/province [17] 0 0
Poruba
Country [18] 0 0
Czechia
State/province [18] 0 0
Brno
Country [19] 0 0
Czechia
State/province [19] 0 0
Olomouc
Country [20] 0 0
Denmark
State/province [20] 0 0
Hovedstaden
Country [21] 0 0
Denmark
State/province [21] 0 0
Aalborg
Country [22] 0 0
Denmark
State/province [22] 0 0
Odense
Country [23] 0 0
Denmark
State/province [23] 0 0
Roskilde
Country [24] 0 0
Denmark
State/province [24] 0 0
Vejle
Country [25] 0 0
Denmark
State/province [25] 0 0
Århus
Country [26] 0 0
France
State/province [26] 0 0
Cedex 5
Country [27] 0 0
France
State/province [27] 0 0
Gironde
Country [28] 0 0
France
State/province [28] 0 0
Meurthe Et Moselle
Country [29] 0 0
France
State/province [29] 0 0
Pays De La Loire
Country [30] 0 0
France
State/province [30] 0 0
Puy De Dome
Country [31] 0 0
France
State/province [31] 0 0
Paris
Country [32] 0 0
Germany
State/province [32] 0 0
Kiel
Country [33] 0 0
Germany
State/province [33] 0 0
Koeln
Country [34] 0 0
Israel
State/province [34] 0 0
Haifa
Country [35] 0 0
Israel
State/province [35] 0 0
Jerusalem
Country [36] 0 0
Israel
State/province [36] 0 0
Petah Tikva
Country [37] 0 0
Israel
State/province [37] 0 0
Ramat Gan
Country [38] 0 0
Israel
State/province [38] 0 0
Tel Aviv-Yafo
Country [39] 0 0
Italy
State/province [39] 0 0
Forli - Cesena
Country [40] 0 0
Italy
State/province [40] 0 0
Lazio
Country [41] 0 0
Italy
State/province [41] 0 0
Bologna
Country [42] 0 0
Italy
State/province [42] 0 0
Brescia
Country [43] 0 0
Italy
State/province [43] 0 0
Milano
Country [44] 0 0
Italy
State/province [44] 0 0
Novara
Country [45] 0 0
Italy
State/province [45] 0 0
Roma
Country [46] 0 0
Netherlands
State/province [46] 0 0
Limburg
Country [47] 0 0
Netherlands
State/province [47] 0 0
South Holland
Country [48] 0 0
Netherlands
State/province [48] 0 0
Amsterdam
Country [49] 0 0
Netherlands
State/province [49] 0 0
Groningen
Country [50] 0 0
Netherlands
State/province [50] 0 0
Utrecht
Country [51] 0 0
Spain
State/province [51] 0 0
Barcelona
Country [52] 0 0
Spain
State/province [52] 0 0
Ferarra
Country [53] 0 0
Spain
State/province [53] 0 0
València
Country [54] 0 0
Spain
State/province [54] 0 0
Madrid
Country [55] 0 0
Spain
State/province [55] 0 0
Sevilla
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Cornwall
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Nottinghamshire
Country [58] 0 0
United Kingdom
State/province [58] 0 0
West Yorkshire
Country [59] 0 0
United Kingdom
State/province [59] 0 0
London

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
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Eli Lilly and Company
Address [2] 0 0
Country [2] 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 Trial Information
Address 0 0
Country 0 0
Phone 0 0
+4570202728
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


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/NCT04623541