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

Follicular Lymphoma Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04663347
• Other study ID #: GCT3013-02
• Secondary ID: 2020-000845-15NL
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 3, 2020
• Est. completion date: March 31, 2029

Study information

• Verified date: May 2024
• Source: Genmab
• Contact: Genmab A/S Trial Information
• Phone: +45 70202728
• Email: clinicaltrials[@]genmab.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, when treating subjects with B-cell non-Hodgkin Lymphoma (B-NHL). The aim of the first part of the trial is to identify the most appropriate dose of epcoritamab, and the aim of the second part of the trial is to assess the selected epcoritamab dose in a larger group of participants with B-NHL. All participants in this trial will receive either epcoritamab alone, or epcoritamab combined with another standard treatment regimen, with a total of 10 different treatment arms being studied. Trial details include: - The total trial duration will be up to 6 years. - The treatment duration for each participant depends upon which arm of treatment they are assigned to receive, but will be no more than 3 years. - The visit frequency for each participant depends upon which arm of treatment they are assigned to receive, but will be weekly to start for all participants, then will decrease to either: every 2 weeks, or every 3 weeks, or every 4 weeks, or every 8 weeks. - All participants will receive active drug; no one will be given placebo. Participants who receive treatment with epcoritamab will have it injected right under the skin. Participants will receive a different regimen of epcoritamab depending upon which arm of treatment they are assigned. Participants who receive standard treatments will have IV infusions and/or oral administration of those treatments. Participants will receive a different standard treatment regimen depending upon which arm of treatment they are assigned. Arm 9 (follicular lymphoma (FL)) is still open for enrolment of new patients, while the other arms have closed their recruitment.

Description:

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 participants with B-NHL. 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) 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 R/R 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 662
• Est. completion date: March 31, 2029
• Est. primary completion date: March 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria

1. 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)

2. Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2

3. Acceptable organ function at screening

4. CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy

5. If of childbearing potential subject must practicing a highly effective method of birth control

6. 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 DLBCL
• DLBCL, not otherwise specified (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 R/R DLBCL and eligible for HDT-ASCT
• DLBCL, NOS
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Arm 5:

• Documented R/R 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:

• Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline
• T-cell/histiocyte rich DLBCL
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B

Arm 9:

• R/R FL
• Progressed within 24 months of initiating first-line treatment

Arm 10:

• Documented R/R DLBCL and eligible for HDT-ASCT
• DLBCL, NOS
• "Double-hit" or "triple-hit" DLBCL
• FL Grade 3B Key Exclusion Criteria

1. Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab

2. Any prior treatment with a bispecific antibody targeting CD3 and CD20.

3. Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab

4. Clinically significant cardiovascular disease

5. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results

6. 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

7. Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection

8. Known history of seropositivity of human immunodeficiency virus (HIV)

9. Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months

10. Neuropathy > grade 1

11. Receiving immunostimulatory agent

12. Prior allogeneic HSCT

13. Current seizure disorder requiring anti-epileptic therapy NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Follicular Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
21-day cycles
• rituximab and lenalidomide
28-day cycles
• rituximab and bendamustine
28-day cycles
• rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
21-day cycles
• gemcitabine and oxaliplatin
28-day cycles

Biological:
• Epcoritamab
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.

Drug:
• rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
21-day cycles
• Lenalidomide
28-day cycles
• rituximab, ifosfamide, carboplatin, and etoposide phosphate
21-day cycles

Biological:
• Epcoritamab
Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
• Epcoritamab
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until disease progression or unacceptable toxicity.
• Epcoritamab
Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
• Epcoritamab
Every week in cycle 1 and then every 8 weeks for a total of 2 years.
• Epcoritamab
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.
• Epcoritamab
Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
• Epcoritamab
Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until transplant or disease progression.

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Austin Health	Heidelberg
Australia	Linear Clinical Research Limited	Nedlands
Belgium	AZ Sint-Jan	Brugge
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	CHU UCL Namur Site Godinne	Yvoir
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Králové
Czechia	Fakultni nemocnice Ostrava	Ostrava - Poruba
Czechia	Fakultni nemocnice v Motole	Prague
Czechia	Vseobecna Fakultni Nemocnice	Praha 2
Denmark	Århus Hospital	Arhus
Denmark	Rigshospitalet	Copenhagen
Denmark	Odense University Hospital	Odense
Denmark	Vejle Sygehus	Vejle
Finland	Tampere University Hospital	Helsinki
Finland	Kuopio University Hospital	Kuopio
Finland	HUS Cancer Center	Lahti
France	Institut Bergonié	Bordeaux
France	CHU Dijon - Hopital du Bocage	Dijon
France	Hopital Claude Huriez - CHRU Lille	Lille
France	Hôpital de la Timone	Marseille
France	Hôpital Saint-Louis	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)	Bergamo
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS	Bologna
Italy	Fondazione del Piemonte per l Oncologia Istituto di Candiolo IRCCS	Candiolo
Italy	Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori	Meldola
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milan
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia	Reggio Emilia
Netherlands	Amsterdam UMC, Locatie VUMC	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen (UMCG)	Groningen
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Erasmus Medisch Centrum	Rotterdam
Netherlands	UMC Utrecht	Utrecht
Norway	Oslo Universitetssykehus HF, Radiumhospitalet	Oslo
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	ICO l Hospitalet	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Sweden	Södra Älvsborgs Sjukhus	Borås
Sweden	Sahlgrenska Sjukhuset	Göteborg
Sweden	Skånes Universitetssjukhus	Lund
Sweden	Karolinska Universitetssjukhuset	Solna
Sweden	Norrlands Universitetssjukhus	Umeå
Sweden	Akademiska Sjukhuset	Uppsala
United Kingdom	University College London Hospitals	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Freeman Hospital	Newcastle Upon Tyne
United Kingdom	Derriford Hospital	Plymouth
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Levine Cancer Center	Charlotte	North Carolina
United States	UT Southwestern Medical Center	Dallas	Texas
United States	John Theurer Cancer Center at Hackensack UMC	Hackensack	New Jersey
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Memorial Sloan Kettering CC	New York	New York
United States	Mount Sinai	New York	New York
United States	UMPC Hillman Cancer Center Cancer Pavillion	Pittsburgh	Pennsylvania
United States	University of California San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Czechia,  Denmark,  Finland,  France,  Italy,  Netherlands,  Norway,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	During the first cycle (Cycle length= 28 days) in each cohort
Primary	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.	From first dose of trial medication to the maximum of 60 days after last dose of epcoritamab or initiation of subsequent anti-lymphoma therapy.
Primary	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.	Up to 3 years
Secondary	Part 1 and 2: Clearance (CL) of Epcoritamab		Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary	Part 1 and 2: Volume of Distribution (Vd) of Epcoritamab		Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary	Part 1 and 2: Area Under the Concentration-Time Curve (AUC) from Time Zero to Last Quantifiable Dose (AUC0-last) of Epcoritamab		Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary	Part 1 and 2: Area Under the Concentration-Time Curve (AUC) from Time Zero to Infinity (AUC0-inf) of Epcoritamab		Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary	Part 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) of Epcoritamab		Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary	Part 1 and 2: Time to Reach Cmax (Tmax) of Epcoritamab		Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary	Part 1 and 2: Terminal Elimination Half-Life (t 1/2) of Epcoritamab		Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary	Part 1 and 2: Plasma Trough (Pre-dose) Concentrations (Ctrough) of Epcoritamab		Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
Secondary	Part 1 and 2: Number of Immune Cell Populations	Immune cell populations in peripheral blood and tumor biopsies will be assessed.	Up to 2 years
Secondary	Part 1 and 2: Percentage of Immune Cell Populations	Immune cell populations in peripheral blood and tumor biopsies will be assessed.	Up to 2 years
Secondary	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.	Up to Cycle 3 (cycle length = 21 days for Arms 1, 4, 8 and 10; cycle length = 28 days for Arms 2, 3, 5, 6 and 9; cycle length = 28 days (Cycle 1) and 56 days (Cycles 2, 3) for Arm 7)
Secondary	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.	Up to 2 years
Secondary	Part 1 and 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Epcoritamab		Up to 3 years
Secondary	Part 1: ORR	ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria.	Up to 3 years
Secondary	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.	Up to 3 years
Secondary	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).	Up to 3 years
Secondary	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.	Up to 3 years
Secondary	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.	Up to 3 years
Secondary	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.	Up to 3 years
Secondary	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.	Up to 3 years
Secondary	Part 1 and 2: Duration of minimal residual disease (MRD) negativity		Up to 3 years
Secondary	Part 2 (Arm 7): Percentage of Participants Who Converted From MRD Positivity to MRD Negativity		Up to 3 years
Secondary	Part 2 (Except Arm 7): Percentage of Participants with Complete Response (CR) in Arms 1 to 10		Up to 3 years
Secondary	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.	Week 24, Week 48, and Week 96
Secondary	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.	Up to 3 years
Secondary	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.	Up to 3 years

External Links

•   Patient website: Recruiting clinical sites in Finland