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JOURNAL ONKOLOGIE – STUDIE
EPCORE™ CLL-1

Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome

Rekrutierend

NCT-Nummer:
NCT04623541

Studienbeginn:
November 2020

Letztes Update:
03.04.2024

Wirkstoff:
Epcoritamab, rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, Venetoclax, Lenalidomide

Indikation (Clinical Trials):
Leukemia, Leukemia, Lymphoid, Leukemia, Lymphocytic, Chronic, B-Cell, Syndrome

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Genmab

Collaborator:
AbbVie

Kontakt

Studienlocations
(3 von 68)

Universitaetsklinikum Schleswig-Holstein- Karl-Lennart-Krebscentrum
24105 Kiel
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Universitaetsklinikum Koeln
50937 Koeln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
O'Neal Comprehensive Cancer Center at University of Alabama at Birmingham
35233 Birmingham
United StatesRekrutierend» Google-Maps
City of Hope National Medical Center
91010 Duarte
United StatesRekrutierend» Google-Maps
Cedars-Sinai Medical Center
90048 Los Angeles
United StatesNoch nicht rekrutierend» Google-Maps
David Geffen School of Medicine
90095 Los Angeles
United StatesRekrutierend» Google-Maps
Stanford Cancer Center
94305 Palo Alto
United StatesRekrutierend» Google-Maps
Memorial Healthcare System
33024 Pembroke Pines
United StatesRekrutierend» Google-Maps
Massachusetts General Hospital
02114 Boston
United StatesRekrutierend» Google-Maps
University of Michigan Comprehensive Cancer Center
48190 Ann Arbor
United StatesRekrutierend» Google-Maps
Henry Ford Medical Group
48202 Detroit
United StatesRekrutierend» Google-Maps
Hackensack Meridian Hospital
07601 Hackensack
United StatesRekrutierend» Google-Maps
Columbia University Hervert Irving Comprehensive Cancer Center
10032 New York
United StatesRekrutierend» Google-Maps
Memorial Sloan Kettering Cancer Center
10065 New York
United StatesRekrutierend» Google-Maps
James Cancer Hospital
43210 Columbus
United StatesRekrutierend» Google-Maps
University of Pennsylvania School of medicine
19104 Philadelphia
United StatesRekrutierend» Google-Maps
The University of Texas Southwestern Medical Centre
75390 Dallas
United StatesRekrutierend» Google-Maps
The University of Texas MD Anderson Cancer Center
77030 Houston
United StatesRekrutierend» Google-Maps
Fred Hutchinson Cancer Research Center
98109 Seattle
United StatesRekrutierend» Google-Maps
Peter MacCallum Cancer Centre
3000 Melbourne
AustraliaRekrutierend» Google-Maps
Fakultni nemocnice Hradec Kralove
500 05 Hradec Králové
CzechiaRekrutierend» Google-Maps
CHU de Montpellier Hôpital Saint Eloi
34090 Montpellier
FranceRekrutierend» Google-Maps
CHU Hôpital Haut-Lévêque Bordeaux
33404 Pessac
FranceRekrutierend» Google-Maps
CHU Hôpital de Brabois Nancy
54500 Vandœuvre-lès-Nancy
FranceRekrutierend» Google-Maps
CHU Clermont Ferrand
63000 Clermont Ferrand cedex
FranceRekrutierend» Google-Maps
Hôpital Universitaire Pitié-Salpêtrière
75013 Paris
FranceRekrutierend» Google-Maps
Hadassah University Hospital - Ein Kerem
Jerusalem
IsraelRekrutierend» Google-Maps
Rabin Medical Center-Beilinson Campus
4941492 Petah Tikva
IsraelRekrutierend» Google-Maps
Tel Aviv Sourasky Medical Center
Tel Aviv-Yafo
IsraelRekrutierend» Google-Maps
IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST
47014 Meldola
ItalyRekrutierend» Google-Maps
IRCCS Policlinico Universitario Agostino Gemelli
00136 Roma
ItalyRekrutierend» Google-Maps
AOU Policlinico Sant'Orsola Malpighi IRCCS
00161 Bologna
ItalyRekrutierend» Google-Maps
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
Brescia
ItalyRekrutierend» Google-Maps
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
00168 Roma
ItalyRekrutierend» Google-Maps
Maastricht University Medical Center
6229 HX Maastricht
NetherlandsRekrutierend» Google-Maps
Albert Schweitzer Ziekenhuis, Dordwijk
3318 AT Dordrecht
NetherlandsRekrutierend» Google-Maps
Universitair Medisch Centrum Groningen
9713 GZ Groningen
NetherlandsRekrutierend» Google-Maps
Universitair Medisch Centrum Utrecht
3584 CX Utrecht
NetherlandsRekrutierend» Google-Maps
Hospital Clinico Universitario de Valencia
46010 Valencia
SpainRekrutierend» Google-Maps
Hospital Clinic de Barcelona
08036 Barcelona
SpainRekrutierend» Google-Maps
Hospital de la Santa Creu i Sant Pau
Barcelona
SpainRekrutierend» Google-Maps
Hospital Universitario Ramón y Cajal
28034 Madrid
SpainRekrutierend» Google-Maps
Hospital Universitario Fundacion Jiménez Díaz
28040 Madrid
SpainRekrutierend» Google-Maps
Royal Cornwall Hospital
TR1 3LJ Truro
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

The purpose of the dose-escalation phase of the trial is to determine the recommended phase 2

dose (RP2D) and the maximum tolerated dose (MTD; if reached) as well as establish the safety

profile of epcoritamab monotherapy and epcoritamab + venetoclax in participants with R/R CLL.

The purpose of the expansion phase is to assess and evaluate the preliminary efficacy, safety

and tolerability profiles of epcoritamab monotherapy and epcoritamab + venetoclax at the RP2D

for patients with R/R CLL/SLL. Along with this, epcoritamab monotherapy, epcoritamab +

lenalidomide and epcoritamab + R-CHOP will be evaluated in patients with RS to assess their

efficacy, safety and tolerability profiles.

Ein-/Ausschlusskriterien

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 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.

Studien-Rationale

Primary outcome:

1. Dose Escalation Phase (R/R CLL arm): Number of Participants with Dose Limiting Toxicities (DLTs) (Time Frame - During the first cycle for low dose cohorts (Cycle length = 28 days) and for high dose cohorts (Cycle length = 35 days)):
DLT events were 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.

2. Dose Escalation Phase: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (Time Frame - From first dose until the end of the safety follow-up period (60 days after last dose))

3. Dose Escalation Phase: Number of Participants with Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and Clinical Tumor Lysis Syndrome (CTLS) (Time Frame - From first dose until the end of the safety follow-up period (60 days after last dose)):
CRS and ICANS will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria. CTLS will be graded according to Cairo-Bishop criteria.

4. Expansion Phase: Overall Response Rate (ORR) (Time Frame - Up to 5 years):
ORR is defined as the percentage of participants who achieve a response of partial response or complete response, prior to initiation of subsequent therapy. R/R CLL participants will be assessed according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and the RS participants according to Lugano criteria.

Secondary outcome:

1. Expansion Phase: Number of Participants with TEAEs and SAEs (Time Frame - From first dose until the end of the safety follow-up period (60 days after last dose))

2. Dose Escalation Phase: ORR (Time Frame - Up to 5 years):
ORR is defined as percentage of participants who achieve a response of partial response or complete response, prior to initiation of subsequent therapy as assessed by iwCLL criteria.

3. Both Phases: Duration of Response (DOR) (Time Frame - Up to 5 years):
DOR is defined among responders, as the time from the initial documentation of response to the date of disease progression or death, whichever occurs earlier.

4. Both Phases: Number of Participants with Complete Remission (CR) / CR with Incomplete Bone Marrow Recovery (CRi) (Time Frame - Up to 5 years):
CR and CRi for R/R CLL participants will be assessed according to iwCLL criteria and CR for the RS participants, according to Lugano criteria.

5. Both Phases: Time to Response (TTR) (Time Frame - Up to 5 years):
TTR is defined among responders, as the time between first dose of epcoritamab and the initial documentation of response.

6. Both Phases: Progression Free Survival (PFS) (Time Frame - Up to 5 years):
PFS is defined as the time from the first dosing date of epcoritamab and the date of disease progression or death, whichever occurs earlier.

7. Both Phases: Overall Survival (OS) (Time Frame - Up to 5 years):
OS is defined as the time from the first dosing date of epcoritamab and the date of death due to any cause.

8. Both Phases: Time to Next Systemic Anti-cancer Therapy (TTNT) (Time Frame - Up to 5 years):
TTNT is defined as the time from the first dosing date of epcoritamab to the first documented administration of subsequent systemic anticancer therapy.

9. Both Phases: Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Sample (AUClast) in Epcoritamab (Time Frame - 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))

10. Both Phases: AUC From Time Zero to Infinity (AUCinf) in Epcoritamab (Time Frame - 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))

11. Both Phases: Maximum (Peak) Plasma Concentration (Cmax) in Epcoritamab (Time Frame - 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))

12. Both Phases: Pre-dose (Trough) Concentrations (Cthrough) in Epcoritamab (Time Frame - 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))

13. Both Phases: Time to Reach Cmax (Tmax) in Epcoritamab (Time Frame - 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))

14. Both Phases: Elimination Half-life (T1/2) in Epcoritamab (Time Frame - 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))

15. Both Phases: Total Body Clearance of Drug From Plasma (CL) in Epcoritamab (Time Frame - 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))

16. Both Phases: Volume of distribution (Vd) in Epcoritamab (Time Frame - 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))

17. Both Phases: Lymphoid Cells for Immunophenotyping (Time Frame - Up to 5 years):
Evaluation of B cells, T cells and their activation

18. Expansion Phase: Number of Participants with CRS, ICANS and CTLS (Time Frame - From first dose until the end of the safety follow-up period (60 days after last dose)):
CRS and ICANS will be graded based on ASTCT criteria. CTLS will be graded according to Cairo-Bishop criteria.

19. Expansion Phase: Percentage of Participants with Minimal Residual Disease (MRD) Negativity (Time Frame - Up to 5 years):
MRD negativity rate, is defined as the proportion of participants with at least 1 undetectable MRD result according to the specific threshold, prior to initiation of subsequent therapy.

20. Both Phases: Number of Participants with Anti-drug Antibodies (ADA) to Epcoritamab (Time Frame - Up to end of treatment period (Up to 2 years))

21. Expansion Phase: Number of Participants with Partial Remission (PR)/Nodular Partial Remission (nPR) (Time Frame - Up to 5 years):
nPR is defined as PR with residual nodules or suspicious lymphocytic infiltrates in participants who are in remission. nPR is only calculated for R/R CLL.

22. Both Phases: Duration of MRD Negativity (Time Frame - Up to 5 years):
The time from first achieving MRD negativity after start of treatment to the MRD conversion to positive.

Studien-Arme

  • 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.

Geprüfte Regime

  • Epcoritamab (EPKINLY™ / GEN3013 / DuoBody®-CD3xCD20 / ):
    Epcoritamab will be administered subcutaneously in cycles of 28 days (except Cycle 1 for high-dose cohorts = 35 days).
  • Epcoritamab (EPKINLY™ / GEN3013 / DuoBody®-CD3xCD20 / ):
    Epcoritamab will be administered subcutaneously in cycles of 21 days (Cycle 1-6) and 28 days for Cycle 7 and beyond.
  • rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone:
    R-CHOP will be administered intravenously in cycles of 21 days for the first 6 cycles.
  • 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.
  • Epcoritamab (EPKINLY™ / GEN3013 / DuoBody®-CD3xCD20 / ):
    Epcoritamab will be administered subcutaneously in cycles of 28 days.
  • Lenalidomide:
    Lenalidomide capsules will be administered once daily for 21 days in each cycle of 28 days up to 12 cycles.

Quelle: ClinicalTrials.gov


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