Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)
- Conditions
- Diffuse Large B-Cell LymphomaFollicular Lymphoma
- Interventions
- Drug: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
- Registration Number
- NCT04663347
- Lead Sponsor
- Genmab
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 543
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 - Epcoritamab + R-CHOP rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone In participants with previously untreated DLBCL. Arm 2 - Epcoritamab + R2 Rituximab and Lenalidomide In participants with R/R FL. Arm 1 - Epcoritamab + R-CHOP Epcoritamab In participants with previously untreated DLBCL. Arm 2 - Epcoritamab + R2 Epcoritamab In participants with R/R FL. Arm 3 - Epcoritamab + BR rituximab and bendamustine In participants with previously untreated FL. Arm 3 - Epcoritamab + BR Epcoritamab In participants with previously untreated FL. Arm 4 - Epcoritamab + R-DHAX/C rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin In participants with R/R DLBCL eligible for ASCT. Arm 4 - Epcoritamab + R-DHAX/C Epcoritamab In participants with R/R DLBCL eligible for ASCT. Arm 5 - Epcoritamab + GemOx gemcitabine and oxaliplatin In participants with R/R DLBCL ineligible ASCT. Arm 5 - Epcoritamab + GemOx Epcoritamab In participants with R/R DLBCL ineligible ASCT. Arm 6 - Epcoritamab + R2 Rituximab and Lenalidomide In participants with previously untreated FL. Arm 6 - Epcoritamab + R2 Epcoritamab In participants with previously untreated FL. Arm 7 - Epcoritamab maintenance Epcoritamab In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L. Arm 8 - Epcoritamab + R mini-CHOP rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline. Arm 8 - Epcoritamab + R mini-CHOP Epcoritamab In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline. Arm 9 - Epcoritamab + Lenalidomide Lenalidomide In participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy. Arm 9 - Epcoritamab + Lenalidomide Epcoritamab In participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy. Arm 10 - Epcoritamab + R-ICE rituximab, ifosfamide, carboplatin, and etoposide phosphate In participants with R/R DLBCL eligible for ASCT. Arm 10 - Epcoritamab + R-ICE Epcoritamab In participants with R/R DLBCL eligible for ASCT.
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants With Dose limiting Toxicities (DLTs) During the first cycle (Cycle length= 28 days) in each cohort 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) 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) 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) Up to 3 years ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.
- Secondary Outcome Measures
Name Time Method Part 1 and 2: Clearance (CL) of Epcoritamab Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) Part 1 and 2: Area Under the Concentration-Time Curve (AUC) of Epcoritamab Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) Part 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) of Epcoritamab Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) Part 1 and 2: Time to Reach Cmax (Tmax) of Epcoritamab Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) 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) Part 1 and 2: Number of Immune Cell Populations Up to 2 years Immune cell populations in peripheral blood and tumor biopsies will be assessed.
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) Part 1 and 2: Percentage of Immune Cell Populations Up to 2 years 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 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) 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) 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 Up to 3 years Part 1: ORR Up to 3 years ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria.
Part 1 and 2: Duration of Response (DOR) Up to 3 years 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) Up to 3 years 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) Up to 3 years 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) Up to 3 years 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) Up to 3 years 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 Up to 3 years 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 Up to 3 years Part 2 (Arm 7): Percentage of Participants Who Converted From MRD Positivity to MRD Negativity Up to 3 years Part 2 (Except Arm 7): Percentage of Participants with Complete Response (CR) in Arms 1 to 10 Up to 3 years Part 2 (Arm 7): Percentage of Participants With CR Week 24, Week 48, and Week 96 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) Up to 3 years 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) Up to 3 years 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.
Trial Locations
- Locations (58)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
John Theurer Cancer Center at Hackensack UMC
🇺🇸Hackensack, New Jersey, United States
Mount Sinai
🇺🇸New York, New York, United States
Memorial Sloan Kettering CC
🇺🇸New York, New York, United States
Levine Cancer Center
🇺🇸Charlotte, North Carolina, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Austin Health
🇦🇺Heidelberg, Australia
Linear Clinical Research Limited
🇦🇺Nedlands, Australia
AZ Sint-Jan
🇧🇪Brugge, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
CHU UCL Namur Site Godinne
🇧🇪Yvoir, Belgium
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Králové, Czechia
Fakultni nemocnice Ostrava
🇨🇿Ostrava - Poruba, Czechia
Fakultni nemocnice v Motole
🇨🇿Prague, Czechia
Vseobecna Fakultni Nemocnice
🇨🇿Praha 2, Czechia
Århus Hospital
🇩🇰Arhus, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Odense University Hospital
🇩🇰Odense, Denmark
Vejle Sygehus
🇩🇰Vejle, Denmark
Tampere University Hospital
🇫🇮Helsinki, Finland
Kuopio University Hospital
🇫🇮Kuopio, Finland
HUS Cancer Center
🇫🇮Lahti, Finland
Hopital Claude Huriez - CHRU Lille
🇫🇷Lille, France
Hôpital de la Timone
🇫🇷Marseille, France
Hôpital Saint-Louis
🇫🇷Paris, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre-Bénite, France
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, Italy
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, Netherlands
Oslo Universitetssykehus HF, Radiumhospitalet
🇳🇴Oslo, Norway
ICO l Hospitalet
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Södra Älvsborgs Sjukhus
🇸🇪Borås, Sweden
Sahlgrenska Sjukhuset
🇸🇪Göteborg, Sweden
Skånes Universitetssjukhus
🇸🇪Lund, Sweden
Karolinska Universitetssjukhuset
🇸🇪Solna, Sweden
Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Freeman Hospital
🇬🇧Newcastle Upon Tyne, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom