EPCORE™ NHL-2: Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

Sponsor

Genmab (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04663347

Collaborator

AbbVie (Industry)

396

Enrollment

Locations

Arms

48.5

Anticipated Duration (Months)

6.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 subjects with B-cell Non-Hodgkin Lymphoma (B-NHL).

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-Cell Lymphoma Follicular Lymphoma	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 Biological: Epcoritamab Maintenance Drug: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone	Phase 1/Phase 2

Detailed Description

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 subjects with previously untreated diffuse large B-cell lymphoma (DLBCL)
Arm 2: epcoritamab + rituximab and lenalidomide (R2) in subjects with relapsed/refractory (R/R) follicular lymphoma (FL)
Arm 3: epcoritamab + rituximab and bendamustine (BR) in subjects with previously untreated FL
Arm 4: epcoritamab + rituximab, cytarabine, dexamethasone, and oxaliplatin/ carboplatin (R-DHAX/C) in subjects with R/R DLBCL eligible for autologous stem cell transplant (ASCT)
Arm 5: epcoritamab + gemcitabine and oxaliplatin (GemOx) in subjects with R/R DLBCL ineligible for ASCT due to age, performance status (PS), or comorbidity
Arm 6: epcoritamab + R2 in subjects with previously untreated FL
Arm 7: epcoritamab maintenance in subjects 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 subjects with previously untreated DLBCL who are ineligible to receive full-dose anthracycline

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. Part 2 includes all 8 arms (Arm 1-8) 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 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

396 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official 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)

Actual Study Start Date :

Nov 16, 2020

Anticipated Primary Completion Date :

Apr 30, 2023

Anticipated Study Completion Date :

Nov 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 - Epcoritamab + R-CHOP In subjects with previously untreated DLBCL	Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone 21-day cycles Other Names: R-CHOP Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy. Other Names: GEN3013; DuoBody®-CD3xCD20
Experimental: Arm 2 - Epcoritamab + R2 In subjects with R/R FL	Drug: rituximab and lenalidomide 28-day cycles Other Names: R2 Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy. Other Names: GEN3013; DuoBody®-CD3xCD20
Experimental: Arm 3 - Epcoritamab + BR In subjects with previously untreated FL	Drug: rituximab and bendamustine 28-day cycles Other Names: BR Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy. Other Names: GEN3013; DuoBody®-CD3xCD20
Experimental: Arm 4 - Epcoritamab + R-DHAX/C In subjects with R/R DLBCL Eligible for ASCT	Drug: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin 21-day cycles Other Names: R-DHAX/C Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy. Other Names: GEN3013; DuoBody®-CD3xCD20
Experimental: Arm 5 - Epcoritamab + GemOx In subjects with R/R DLBCL Ineligible ASCT	Drug: gemcitabine and oxaliplatin 28-day cycles Other Names: GemOx Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy. Other Names: GEN3013; DuoBody®-CD3xCD20
Experimental: Arm 6 - Epcoritamab + R2 In subjects with previously untreated FL	Drug: rituximab and lenalidomide 28-day cycles Other Names: R2 Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy. Other Names: GEN3013; DuoBody®-CD3xCD20
Experimental: Arm 7 - Epcoritamab maintenance In subjects with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L	Biological: Epcoritamab Maintenance 28-day cycle for Cycle 1 and then 56-day cycle from Cycle 2 through 13 Other Names: GEN3013; DuoBody®-CD3xCD20
Experimental: Arm 8 - Epcoritamab + R mini-CHOP In subjects with previously untreated DLBCL who are ineligible to receive full-dose anthracycline	Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy. Other Names: GEN3013; DuoBody®-CD3xCD20 Drug: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone 21-day cycle Other Names: R mini-CHOP

Outcome Measures

Primary Outcome Measures

Part 1: DLTs [During the first treatment cycle (28 days) in each cohort]
To identify the recommended phase 2 dose (RP2D) and if reached, the Maximum Tolerated Dose (MTD).
Part 1 and Part 2: Incidence of adverse events [From first dose of trial medication to the maximum of 60 days after last dose of epcoritamab or initiation of subsequent anti-lymphoma therapy.]
To assess the safety and tolerability of GEN3013 as monotherapy and in combination with other agents.
Part 1 and Part 2: Incidence of adverse events [From first dose of trial medication to the maximum of 30 days after the last dose of any SOC medication or initiation of subsequent anti-lymphoma therapy.]
To assess the safety and tolerability of GEN3013 as monotherapy and in combination with other agents.
Part 1 and Part 2: Incidence and severity of changes in laboratory values [From screening until 60 days after last dose, approximately 24 months]
Clinical laboratory parameters assessed: hematology, chemistry, coagulation, tumor lysis, immunoglobulins, and urinalyses
Part 1 and Part 2: Incidence of dose interruptions and delays [From first dose until end of treatment, approximately 24 months]
Assess the duration of exposure for epcoritamab and combination agents
Part 2: Overall Response Rate (ORR) [From 6 weeks after enrollment until treatment discontinuation, assessed up to 3 years]
Assess the preliminary anti-tumor activity of epcoritamab in combination with other agents

Secondary Outcome Measures

Total body clearance of drug from the plasma (CL) [From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years)]
Volume of Distribution [From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years)]
Area Under the Concentration-Time Curve (AUC) from Time 0 to last quantifiable sample [From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years)]
Area Under the Concentration-Time Curve (AUC) from Time 0 to infinity [From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years)]
Maximum observed concentration (Cmax) [From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years)]
Time to reach Cmax (Tmax) [From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years)]
Terminal Elimination Half-Life (t 1/2) [From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years)]
Trough concentrations (Ctrough) [From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years)]
Incidence of anti-drug antibodies (ADAs) to epcoritamab [From first dose until end of treatment, approximately 24 months]
To evaluate immunogenicity
Duration of response (DOR) [Approximately 3 years after the last subject's first dose]
To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Time to response (TTR) [Approximately 3 years after the last subject's first dose]
To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Progressive-free survival (PFS) [Approximately 3 years after the last subject's first dose]
To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Overall survival (OS) [Approximately 3 years after the last subject's first dose]
To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Time to next anti-lymphoma therapy (TTNT) [Approximately 3 years after the last subject's first dose]
To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Rate of minimal residual disease (MRD) negativity [Approximately 3 years after the last subject's first dose]
To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Duration of minimal residual disease (MRD) negativity [Approximately 3 years after the last subject's first dose]
To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria

Subject must sign an Informed Consent Form (ICF)
At least 18 years of age
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)
Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
Acceptable organ function at screening
CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
If of childbearing potential subject must practicing a highly effective method of birth control
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 Documented diffuse large B-cell lymphoma (DLBCL)
DLBCL, 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 DLBCL and eligible for HDT-ASCT
DLBCL, NOS
"double-hit" or "triple-hit" DLBCL
FL Grade 3B

Arm 5:

Relapsed or refractory documented 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:

DLBCL, NOS
T-cell/histiocyte rich DLBCL
"double-hit" or "triple-hit" DLBCL
FL Grade 3B

Key Exclusion Criteria

Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
Any prior treatment with a bispecific antibody targeting CD3 and CD20.
Treatment with CAR-T therapy within 30 days prior to first dose of epcoritamab
Clinically significant cardiovascular disease
Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
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
Active positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
Known history of seropositivity of human immunodeficiency virus (HIV)
Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
Neuropathy > grade 1
Receiving immunostimulatory agent
Prior allogeneic HSCT
Current seizure disorder requiring anti-epileptic therapy

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
3	David Geffen School of Medicine at UCLA	Los Angeles	California	United States	90095
4	University of California San Francisco	San Francisco	California	United States	94143
5	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	84109
7	John Theurer Cancer Center at Hackensack UMC	Hackensack	New Jersey	United States	07601
8	Mount Sinai	New York	New York	United States	10029
9	Memorial Sloan Kettering CC	New York	New York	United States	10065
10	Levine Cancer Center	Charlotte	North Carolina	United States	28204
11	UMPC Hillman Cancer Center Cancer Pavillion	Pittsburgh	Pennsylvania	United States	15232
12	UT Southwestern Medical Center	Dallas	Texas	United States	75390
13	Austin Health	Heidelberg	Victoria	Australia	3084
14	Austin Health	Heidelberg		Australia	VIC 3084
15	Linear Clinical Research Limited	Nedlands		Australia	6009
16	AZ Sint-Jan	Brugge		Belgium	8000
17	Universitair Ziekenhuis Gent	Gent		Belgium	9000
18	CHU UCL Namur Site Godinne	Yvoir		Belgium	5530
19	Fakultni nemocnice Hradec Kralove	Hradec Králové		Czechia
20	Fakultni nemocnice v Motole	Prague		Czechia	15006
21	Århus Hospital	Arhus		Denmark
22	Rigshospitalet	Copenhagen		Denmark	2100
23	Odense University Hospital	Odense		Denmark
24	Vejle Sygehus	Vejle		Denmark
25	Tampere University Hospital	Helsinki		Finland	33520
26	Kuopio University Hospital	Kuopio		Finland	70210
27	HUS Cancer Center	Lahti		Finland	15850
28	CHU Dijon - Hopital du Bocage	Dijon		France	21000
29	Institut Bergonié	Gironde		France	33076
30	Centre Hospitalier Lyon Sud	Lyon		France
31	Hôpital de la Timone	Marseille		France	13005
32	Hopital Claude Huriez - CHRU Lille	Nordausques		France	59037
33	Hôpital Saint-Louis	Paris		France	75475
34	Centre Hospitalier Lyon Sud	Pierre-Bénite		France	69495
35	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)	Bergamo		Italy	24127
36	Fondazione del Piemonte per l Oncologia Istituto di Candiolo IRCCS	Candiolo		Italy	10060
37	Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori	Meldola		Italy	47014
38	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milan		Italy	20122
39	Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100
40	Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia	Reggio Emilia		Italy	42123
41	Amsterdam UMC, Locatie VUMC	Amsterdam		Netherlands	1105 AZ
42	Universitair Medisch Centrum Groningen (UMCG)	Groningen		Netherlands	9713
43	Leids Universitair Medisch Centrum	Leiden		Netherlands	2333 ZA
44	Maastricht University Medical Center	Maastricht		Netherlands	6229 HX
45	Erasmus Medisch Centrum	Rotterdam		Netherlands
46	UMC Utrecht	Utrecht		Netherlands	3584
47	Oslo Universitetssykehus HF, Radiumhospitalet	Oslo		Norway	310
48	ICO l Hospitalet	Barcelona		Spain	08908
49	Hospital Universitari Vall d'Hebron	Barcelona		Spain	8035
50	Hospital Universitario Fundacion Jimenez Diaz	Madrid		Spain	28040
51	Hospital Universitario La Paz	Madrid		Spain	28046
52	Hospital Universitario de Salamanca	Salamanca		Spain	37007
53	Södra Älvsborgs Sjukhus	Borås		Sweden
54	Sahlgrenska Sjukhuset	Göteborg		Sweden	413 45
55	Skånes Universitetssjukhus	Lund		Sweden
56	Karolinska Universitetssjukhuset	Solna		Sweden
57	Norrlands Universitetssjukhus	Umeå		Sweden
58	Akademiska Sjukhuset	Uppsala		Sweden
59	University College London Hospitals	London		United Kingdom	NW1 2PG
60	The Christie NHS Foundation Trust	Manchester		United Kingdom
61	Freeman Hospital	Newcastle Upon Tyne		United Kingdom	NE7 7D
62	Derriford Hospital	Plymouth		United Kingdom	PL6 8DH