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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
Date last updated
5/11/2024

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
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

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.


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 (Cycle 1-6) and 28 days for Cycle 7 and beyond.

Treatment: Drugs: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
R-CHOP will be administered intravenously in cycles of 21 days for the first 6 cycles.

Treatment: Drugs: Venetoclax
Venetoclax tablets will be administered orally once daily during the 5-week ramp up period and during Cycle 1-26 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 up to 12 cycles.
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 (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: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [2] 0 0
From first dose until the end of the safety follow-up period (60 days after last dose)
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
From first dose until the end of the safety follow-up period (60 days after last dose)
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
From first dose until the end of the safety follow-up period (60 days after last dose)
Secondary outcome [2] 0 0
Dose Escalation Phase: ORR
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Both Phases: Duration of Response (DOR)
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Both Phases: Number of Participants with Complete Remission (CR) / CR with Incomplete Bone Marrow Recovery (CRi)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Both Phases: Time to Response (TTR)
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Both Phases: Progression Free Survival (PFS)
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Both Phases: Overall Survival (OS)
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
Both Phases: Time to Next Systemic Anti-cancer Therapy (TTNT)
Timepoint [8] 0 0
Up to 5 years
Secondary outcome [9] 0 0
Both Phases: Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Sample (AUClast) 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)
Secondary outcome [10] 0 0
Both Phases: AUC From Time Zero to Infinity (AUCinf) 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)
Secondary outcome [11] 0 0
Both Phases: Maximum (Peak) Plasma Concentration (Cmax) 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)
Secondary outcome [12] 0 0
Both Phases: Pre-dose (Trough) Concentrations (Cthrough) 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)
Secondary outcome [13] 0 0
Both Phases: Time to Reach Cmax (Tmax) 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)
Secondary outcome [14] 0 0
Both Phases: Elimination Half-life (T1/2) 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)
Secondary outcome [15] 0 0
Both Phases: Total Body Clearance of Drug From Plasma (CL) in Epcoritamab
Timepoint [15] 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)
Secondary outcome [16] 0 0
Both Phases: Volume of distribution (Vd) in Epcoritamab
Timepoint [16] 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)
Secondary outcome [17] 0 0
Both Phases: Lymphoid Cells for Immunophenotyping
Timepoint [17] 0 0
Up to 5 years
Secondary outcome [18] 0 0
Expansion Phase: Number of Participants with CRS, ICANS and CTLS
Timepoint [18] 0 0
From first dose until the end of the safety follow-up period (60 days after last dose)
Secondary outcome [19] 0 0
Expansion Phase: Percentage of Participants with Minimal Residual Disease (MRD) Negativity
Timepoint [19] 0 0
Up to 5 years
Secondary outcome [20] 0 0
Both Phases: Number of Participants with Anti-drug Antibodies (ADA) to Epcoritamab
Timepoint [20] 0 0
Up to end of treatment period (Up to 2 years)
Secondary outcome [21] 0 0
Expansion Phase: Number of Participants with Partial Remission (PR)/Nodular Partial Remission (nPR)
Timepoint [21] 0 0
Up to 5 years
Secondary outcome [22] 0 0
Both Phases: Duration of MRD Negativity
Timepoint [22] 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. For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
5. For R/R CLL arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor.
6. For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
7. 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.
8. For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
9. Life expectancy >3 months on standard of care (SOC).
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
12. For RS - R-CHOP combination Therapy Arm -

* Eligible for treatment with R-CHOP.
13. For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy.

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 (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of epcoritamab.
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. Active hepatitis B virus or active hepatitis C.
10. Known history of HIV.
11. For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
12. Received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial and progressed on treatment.
13. For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
14. RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS.

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
184
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

Ethics approval
Ethics application status

Summary
Brief summary
The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20). Epcoritamab will either be studied as:

* Monotherapy, or
* Combination therapy:

* epcoritamab + venetoclax
* epcoritamab + lenalidomide
* epcoritamab + R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine (Oncovin®) and prednisone).

The study includes patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL)/small lymphocytic lymphoma (SLL) and patients with Richter's Syndrome (RS).

Study participants with R/R CLL/SLL are treated either with epcoritamab as monotherapy or epcoritamab + venetoclax. Study participants with RS are treated either with epcoritamab as monotherapy or epcoritamab + lenalidomide or epcoritamab + R-CHOP. The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Patients with RS are only included in the expansion phase.

Epcoritamab will be injected subcutaneously (under the skin). Standard-of-care and combination treatments (venetoclax, lenalidomide, and R-CHOP) will be given either orally (by mouth) or intravenously (in a vein).

Study details include:

* Study duration will be up to 5 years.
* The treatment duration for each participant will be between 18 months (1.5 years) and 24 months (2 years), depending upon the treatment arm assigned.
* The visit frequency will be either weekly, every other week, or monthly, depending upon the part of the study.

All participants will receive active drug; no one will be given placebo.
Trial website
https://clinicaltrials.gov/study/NCT04623541
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04623541