Clinical trial NCT04663347: Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Follicular Lymphoma
Keywords: DuoBody®
monoclonal antibodies
anti-CD3
anti-CD20
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: AbbVie
First posted: 2020-12-11
Enrollment: 543
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 participants 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 treatment duration for each participant depends upon which arm of treatment they are assigned to.
* The visit frequency for each participant depends upon which arm of treatment they are assigned to, 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 intravenous (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.

Detailed 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) 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) following first or second line 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. Participants 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 participants in Arm 8 during a 28-day period (safety run-in). The arms are conducted in parallel.

Eligibility criteria: 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). Applies to all arms except arm 7.
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 participant 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.

Primary outcomes:
measure: Part 1: Number of Participants With Dose limiting Toxicities (DLTs)
timeFrame: During the first cycle (Cycle length= 28 days) in each cohort
measure: Part 1 and Part 2 (Arm 7): Number of Participants With Adverse Events (AEs)
timeFrame: From first dose of drug until either 60 days after last dose, date participant withdraws consent, date participant starts a new systemic anticancer therapy, or date participant dies, whichever occurs first (up to approximately 3 years)
measure: Part 2 (Except Arm 7): Overall Response Rate (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Part 1 and 2: Clearance (CL) of Epcoritamab
timeFrame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
measure: Part 1 and 2: Area Under the Concentration-Time Curve (AUC) of Epcoritamab
timeFrame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
measure: Part 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) of Epcoritamab
timeFrame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
measure: Part 1 and 2: Time to Reach Cmax (Tmax) of Epcoritamab
timeFrame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
measure: Part 1 and 2: Terminal Elimination Half-Life (t 1/2) of Epcoritamab
timeFrame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
measure: Part 1 and 2: Plasma Trough (Pre-dose) Concentrations (Ctrough) of Epcoritamab
timeFrame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years)
measure: Part 1 and 2: Number of Immune Cell Populations
timeFrame: Up to 2 years
measure: Part 1 and 2: Percentage of Immune Cell Populations
timeFrame: Up to 2 years
measure: Part 1 and 2: Change From Baseline in Cytokine Levels up to Cycle 3
timeFrame: 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)
measure: Part 1 and 2: Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (DNA) Level up to End of Treatment (up to 2 Years)
timeFrame: Up to 2 years
measure: Part 1 and 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Epcoritamab
timeFrame: Up to 3 years
measure: Part 1: ORR
timeFrame: Up to 3 years
measure: Part 1 and 2: Duration of Response (DOR)
timeFrame: Up to 3 years
measure: Part 1 and 2: Time to Response (TTR)
timeFrame: Up to 3 years
measure: Part 1 and 2: Progression Free Survival (PFS)
timeFrame: Up to 3 years
measure: Part 1 and 2: Overall Survival (OS)
timeFrame: Up to 3 years
measure: Part 1 and 2: Time to Next Anti-lymphoma Therapy (TTNT)
timeFrame: Up to 3 years
measure: Part 1 and 2: Percentage of Participants With Minimal Residual Disease (MRD) Negativity
timeFrame: Up to 3 years
measure: Part 1 and 2: Duration of minimal residual disease (MRD) negativity
timeFrame: Up to 3 years
measure: Part 2 (Arm 7): Percentage of Participants Who Converted From MRD Positivity to MRD Negativity
timeFrame: Up to 3 years
measure: Part 2 (Except Arm 7): Percentage of Participants with Complete Response (CR) in Arms 1 to 10
timeFrame: Up to 3 years
measure: Part 2 (Arm 7): Percentage of Participants With CR
timeFrame: Week 24, Week 48, and Week 96
measure: Part 1 and 2: Time to Complete Response (TTCR)
timeFrame: Up to 3 years
measure: Part 1 and 2: Duration of Complete Response (DoCR)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack UMC
state: New Jersey
city: New York
country: United States
facility: Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering CC
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Center
state: North Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Heidelberg
country: Australia
facility: Austin Health
city: Nedlands
country: Australia
facility: Linear Clinical Research Limited
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Yvoir
country: Belgium
facility: CHU UCL Namur Site Godinne
city: Hradec Králové
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Ostrava - Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Prague
country: Czechia
facility: Fakultni nemocnice v Motole
city: Praha 2
country: Czechia
facility: Vseobecna Fakultni Nemocnice
city: Arhus
country: Denmark
facility: Århus Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Vejle
country: Denmark
facility: Vejle Sygehus
city: Helsinki
country: Finland
facility: Tampere University Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Lahti
country: Finland
facility: HUS Cancer Center
city: Lille
country: France
facility: Hopital Claude Huriez - CHRU Lille
city: Marseille
country: France
facility: Hôpital de la Timone
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l Oncologia Istituto di Candiolo IRCCS
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
city: Milan
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, Locatie VUMC
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen (UMCG)
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Radiumhospitalet
city: Barcelona
country: Spain
facility: ICO l Hospitalet
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Borås
country: Sweden
facility: Södra Älvsborgs Sjukhus
city: Göteborg
country: Sweden
facility: Sahlgrenska Sjukhuset
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
References: