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

Primary Purpose

Diffuse Large B-Cell Lymphoma, Follicular Lymphoma

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

rituximab and lenalidomide

rituximab and bendamustine

rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin

gemcitabine and oxaliplatin

Epcoritamab

rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone

Lenalidomide

rituximab, ifosfamide, carboplatin, and etoposide phosphate

Epcoritamab

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring DuoBody®, monoclonal antibodies, anti-CD3, anti-CD20

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

University of Alabama at BirminghamRecruiting
Cedars-Sinai Medical CenterRecruiting
David Geffen School of Medicine at UCLARecruiting
University of California San FranciscoRecruiting
Dana Farber Cancer InstituteRecruiting
University of Michigan Comprehensive Cancer CenterRecruiting
John Theurer Cancer Center at Hackensack UMCRecruiting
Mount SinaiRecruiting
Memorial Sloan Kettering CCRecruiting
Levine Cancer CenterRecruiting
UMPC Hillman Cancer Center Cancer PavillionRecruiting
UT Southwestern Medical CenterRecruiting
Monash Medical Centre
Austin HealthRecruiting
Linear Clinical Research LimitedRecruiting
AZ Sint-JanRecruiting
Universitair Ziekenhuis GentRecruiting
CHU UCL Namur Site GodinneRecruiting
Fakultni nemocnice Hradec KraloveRecruiting
Fakultni nemocnice OstravaRecruiting
Fakultni nemocnice v MotoleRecruiting
Vseobecna Fakultni NemocniceRecruiting
Århus HospitalRecruiting
RigshospitaletRecruiting
Odense University HospitalRecruiting
Vejle SygehusRecruiting
Tampere University HospitalRecruiting
Kuopio University HospitalRecruiting
HUS Cancer CenterRecruiting
Institut BergoniéRecruiting
CHU Dijon - Hopital du BocageRecruiting
Hopital Claude Huriez - CHRU LilleRecruiting
Hôpital de la TimoneRecruiting
Hôpital Saint-LouisRecruiting
Centre Hospitalier Lyon SudRecruiting
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)Recruiting
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCSRecruiting
Fondazione del Piemonte per l Oncologia Istituto di Candiolo IRCCSRecruiting
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei TumoriRecruiting
Fondazione IRCCS CA' Granda Ospedale Maggiore PoliclinicoRecruiting
Fondazione IRCCS Policlinico San MatteoRecruiting
Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio EmiliaRecruiting
Amsterdam UMC, Locatie VUMCRecruiting
Universitair Medisch Centrum Groningen (UMCG)Recruiting
Leids Universitair Medisch CentrumRecruiting
Maastricht University Medical CenterRecruiting
Erasmus Medisch CentrumRecruiting
UMC UtrechtRecruiting
Oslo Universitetssykehus HF, RadiumhospitaletRecruiting
ICO l HospitaletRecruiting
Hospital Universitari Vall d'HebronRecruiting
Hospital Universitario Fundacion Jimenez DiazRecruiting
Hospital Universitario La PazRecruiting
Hospital Universitario de SalamancaRecruiting
Södra Älvsborgs SjukhusRecruiting
Sahlgrenska SjukhusetRecruiting
Skånes UniversitetssjukhusRecruiting
Karolinska UniversitetssjukhusetRecruiting
Norrlands UniversitetssjukhusRecruiting
Akademiska SjukhusetRecruiting
University College London Hospitals
The Christie NHS Foundation TrustRecruiting
Freeman HospitalRecruiting
Derriford HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Arm Label

Arm 1 - Epcoritamab + R-CHOP

Arm 2 - Epcoritamab + R2

Arm 3 - Epcoritamab + BR

Arm 4 - Epcoritamab + R-DHAX/C

Arm 5 - Epcoritamab + GemOx

Arm 6 - Epcoritamab + R2

Arm 7 - Epcoritamab maintenance

Arm 8 - Epcoritamab + R mini-CHOP

Arm 9 - Epcoritamab + Lenalidomide

Arm 10 - Epcoritamab + R-ICE

Arm Description

In participants with previously untreated DLBCL.

In participants with R/R FL.

In participants with previously untreated FL.

In participants with R/R DLBCL eligible for ASCT.

In participants with R/R DLBCL ineligible ASCT.

In participants with previously untreated FL.

In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L.

In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline.

In participants with FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy.

In participants with R/R DLBCL eligible for ASCT.

Outcomes

Primary Outcome Measures

Part 1: Number of Participants With Dose limiting Toxicities (DLTs)

DLT events are 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.

Part 1 and Part 2 (Arm 7): Number of Participants With Adverse Events (AEs)

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign. (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Part 2 (Except Arm 7): Overall Response Rate (ORR)

ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.

Secondary Outcome Measures

Part 1 and 2: Clearance (CL) of Epcoritamab

Part 1 and 2: Volume of Distribution (Vd) of Epcoritamab

Part 1 and 2: Area Under the Concentration-Time Curve (AUC) from Time Zero to Last Quantifiable Dose (AUC0-last) of Epcoritamab

Part 1 and 2: Area Under the Concentration-Time Curve (AUC) from Time Zero to Infinity (AUC0-inf) of Epcoritamab

Part 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) of Epcoritamab

Part 1 and 2: Time to Reach Cmax (Tmax) of Epcoritamab

Part 1 and 2: Terminal Elimination Half-Life (t 1/2) of Epcoritamab

Part 1 and 2: Plasma Trough (Pre-dose) Concentrations (Ctrough) of Epcoritamab

Part 1 and 2: Number of Immune Cell Populations

Immune cell populations in peripheral blood and tumor biopsies will be assessed.

Part 1 and 2: Percentage of Immune Cell Populations

Immune cell populations in peripheral blood and tumor biopsies will be assessed.

Part 1 and 2: Change From Baseline in Cytokine Levels up to Cycle 3

Change in cytokine levels in peripheral blood samples will be assessed.

Part 1 and 2: Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (DNA) Level up to End of Treatment (up to 2 Years)

Change in circulating tumor DNA levels will be assessed.

Part 1 and 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Epcoritamab

Part 1: ORR

ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria.

Part 1 and 2: Duration of Response (DOR)

DOR: the time from the first documentation of objective tumor response (CR or PR) to the date of first PD or death based on Lugano criteria.

Part 1 and 2: Time to Response (TTR)

TTR is defined as the time from Day 1 of Cycle 1 to first documentation of objective tumor response (CR or PR).

Part 1 and 2: Progression Free Survival (PFS)

PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause based on Lugano criteria.

Part 1 and 2: Overall Survival (OS)

OS is defined as the time from the date of first dose, to the date of death due to any cause.

Part 1 and 2: Time to Next Anti-lymphoma Therapy (TTNT)

TTNT is defined as the time from Day 1 of Cycle 1 to first documented administration of subsequent anti-lymphoma therapy.

Part 1 and 2: Percentage of Participants With Minimal Residual Disease (MRD) Negativity

It is defined as the percentage of participants with at least 1 MRD negative result.

Part 1 and 2: Duration of minimal residual disease (MRD) negativity

Part 2 (Arm 7): Percentage of Participants Who Converted From MRD Positivity to MRD Negativity

Part 2 (Except Arm 7): Percentage of Participants with Complete Response (CR) in Arms 1 to 10

Part 2 (Arm 7): Percentage of Participants With CR

It is defined as the percentage of participants who remain in complete remission or converting to complete remission after first trial drug administration.

Part 1 and 2: Time to Complete Response (TTCR)

TTCR is defined as the time from first trial drug administration to the date of first documented complete response post-treatment.

Part 1 and 2: Duration of Complete Response (DoCR)

DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs first based on Lugano criteria.

Full Information

NCT ID

NCT04663347

First Posted

October 27, 2020

Last Updated

August 7, 2023

Sponsor

Genmab

Collaborators

AbbVie

1. Study Identification

Unique Protocol Identification Number

NCT04663347

Brief Title

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

Acronym

EPCORE™ NHL-2

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)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 3, 2020 (Actual)

Primary Completion Date

March 31, 2029 (Anticipated)

Study Completion Date

March 31, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Genmab

Collaborators

AbbVie

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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 (EPKINLY™) in combination with other standard of care (SOC) agents in participants with B-cell Non-Hodgkin Lymphoma (B-NHL).

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 participants with previously untreated diffuse large B-cell lymphoma (DLBCL) Arm 2: epcoritamab + rituximab and lenalidomide (R2) in participants with relapsed/refractory (R/R) follicular lymphoma (FL) Arm 3: epcoritamab + rituximab and bendamustine (BR) in participants with previously untreated FL Arm 4: epcoritamab + rituximab, cytarabine, dexamethasone, and oxaliplatin/ carboplatin (R-DHAX/C) in participants with R/R DLBCL eligible for autologous stem cell transplant (ASCT) Arm 5: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants with R/R DLBCL ineligible for ASCT due to age, performance status (PS), or comorbidity Arm 6: epcoritamab + R2 in participants with previously untreated FL Arm 7: epcoritamab maintenance in participants 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 participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline Arm 9: epcoritamab + lenalidomide for second-line treatment in participants with FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy Arm 10: epcoritamab + rituximab, ifosfamide, carboplatin, and etoposide phosphate (R-ICE) in participants with R/R DLBCL eligible for ASCT 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 and Arm 10. Part 2 includes all 10 arms (Arm 1-10) 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 and Arm 10 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diffuse Large B-Cell Lymphoma, Follicular Lymphoma

Keywords

DuoBody®, monoclonal antibodies, anti-CD3, anti-CD20

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

662 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm 1 - Epcoritamab + R-CHOP

Arm Type

Experimental

Arm Description

In participants with previously untreated DLBCL.

Arm Title

Arm 2 - Epcoritamab + R2

Arm Type

Experimental

Arm Description

In participants with R/R FL.

Arm Title

Arm 3 - Epcoritamab + BR

Arm Type

Experimental

Arm Description

In participants with previously untreated FL.

Arm Title

Arm 4 - Epcoritamab + R-DHAX/C

Arm Type

Experimental

Arm Description

In participants with R/R DLBCL eligible for ASCT.

Arm Title

Arm 5 - Epcoritamab + GemOx

Arm Type

Experimental

Arm Description

In participants with R/R DLBCL ineligible ASCT.

Arm Title

Arm 6 - Epcoritamab + R2

Arm Type

Experimental

Arm Description

In participants with previously untreated FL.

Arm Title

Arm 7 - Epcoritamab maintenance

Arm Type

Experimental

Arm Description

In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L.

Arm Title

Arm 8 - Epcoritamab + R mini-CHOP

Arm Type

Experimental

Arm Description

In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline.

Arm Title

Arm 9 - Epcoritamab + Lenalidomide

Arm Type

Experimental

Arm Description

In participants with FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy.

Arm Title

Arm 10 - Epcoritamab + R-ICE

Arm Type

Experimental

Arm Description

In participants with R/R DLBCL eligible for ASCT.

Intervention Type

Drug

Intervention Name(s)

rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

Other Intervention Name(s)

R-CHOP

Intervention Description

21-day cycles

Intervention Type

Drug

Intervention Name(s)

rituximab and lenalidomide

Other Intervention Name(s)

Intervention Description

28-day cycles

Intervention Type

Drug

Intervention Name(s)

rituximab and bendamustine

Other Intervention Name(s)

Intervention Description

28-day cycles

Intervention Type

Drug

Intervention Name(s)

rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin

Other Intervention Name(s)

R-DHAX/C

Intervention Description

21-day cycles

Intervention Type

Drug

Intervention Name(s)

gemcitabine and oxaliplatin

Other Intervention Name(s)

GemOx

Intervention Description

28-day cycles

Intervention Type

Biological

Intervention Name(s)

Epcoritamab

Other Intervention Name(s)

GEN3013, DuoBody®-CD3xCD20, EPKINLY™

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone

Other Intervention Name(s)

R mini-CHOP

Intervention Description

21-day cycles

Intervention Type

Drug

Intervention Name(s)

Lenalidomide

Intervention Description

28-day cycles

Intervention Type

Drug

Intervention Name(s)

rituximab, ifosfamide, carboplatin, and etoposide phosphate

Other Intervention Name(s)

R-ICE

Intervention Description

21-day cycles

Intervention Type

Biological

Intervention Name(s)

Epcoritamab

Other Intervention Name(s)

GEN3013, DuoBody®-CD3xCD20, EPKINLY™

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Epcoritamab

Other Intervention Name(s)

GEN3013, DuoBody®-CD3xCD20, EPKINLY™

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Epcoritamab

Other Intervention Name(s)

GEN3013, DuoBody®-CD3xCD20, EPKINLY™

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Epcoritamab

Other Intervention Name(s)

GEN3013, DuoBody®-CD3xCD20, EPKINLY™

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Epcoritamab

Other Intervention Name(s)

GEN3013, DuoBody®-CD3xCD20, EPKINLY™

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Epcoritamab

Other Intervention Name(s)

GEN3013, DuoBody®-CD3xCD20, EPKINLY™

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Epcoritamab

Other Intervention Name(s)

GEN3013, DuoBody®-CD3xCD20, EPKINLY™

Intervention Description

Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until transplant or disease progression.

Primary Outcome Measure Information:

Title

Part 1: Number of Participants With Dose limiting Toxicities (DLTs)

Description

Time Frame

During the first cycle (Cycle length= 28 days) in each cohort

Title

Part 1 and Part 2 (Arm 7): Number of Participants With Adverse Events (AEs)

Description

Time Frame

From first dose of trial medication to the maximum of 60 days after last dose of epcoritamab or initiation of subsequent anti-lymphoma therapy.

Title

Part 2 (Except Arm 7): Overall Response Rate (ORR)

Description

ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.

Time Frame

Up to 3 years

Secondary Outcome Measure Information:

Title

Part 1 and 2: Clearance (CL) of Epcoritamab

Time Frame