Subcutaneous Epcoritamab With or Without Lenalidomide as First Line Therapy for Diffuse Large B-Cell Lymphoma
- Conditions
- Diffuse Large B-Cell Lymphoma
- Interventions
- Registration Number
- NCT05660967
- Lead Sponsor
- Genmab
- Brief Summary
The purpose of the study is to examine efficacy and safety of epcoritamab with and without lenalidomide in newly diagnosed elderly patients with Diffuse Large B-Cell Lymphoma (DLBCL) who cannot tolerate anthracycline therapy. Epcoritamab (also known as EPKINLY™, GEN3013 and DuoBody®-CD3xCD20) is an antibody that has already been tested in several clinical studies. All patients will receive active treatment. There is an equal chance of receiving epcoritamab or epcoritamab plus lenalidomide.
- Detailed Description
This is an open-label, multicenter, global phase-2 trial evaluating the efficacy and safety of epcoritamab monotherapy and epcoritamab plus lenalidomide in elderly patients who are deemed anthracycline ineligible.
The trial is designed in two stages:
* Stage 1 which includes a safety run-in phase in each arm
* Stage 2, an expansion of the selected treatment from Stage 1
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 180
-
Must have newly diagnosed CD20+ large cell lymphoma.
-
Is ineligible for anthracycline-based therapy/cytotoxic chemotherapy due to:
- Being age ≥80 years; AND/OR
- Being age ≥75 years and having important comorbid condition(s), which are likely to have a negative impact on tolerability of anthracycline-based therapy/cytotoxic chemotherapy.
-
Have Immune Effector Cell-Associated Encephalopathy (ICE) score of at least 8 out of 10.
-
Have Ann Arbor Stage II-IV disease.
-
Have ECOG PS of 0, 1, or 2; (ECOG PS of 3 may be considered if impairment is attributed to current lymphoma/DLBCL and if pre-phase treatment during the screening phase results in an improvement of ECOG PS to ≤2 prior to enrollment).
-
Have measurable disease as per Lugano criteria.
-
Have acceptable organ function based on baseline bloodwork.
-
Must have fresh (preferred) or archival biopsy material at screening.
-
Has known active, clinically significant bacterial, viral, fungal, mycobacterial, parasitic, or other infection at trial enrollment, including COVID-19 infection.
-
Has severe cardiovascular disease (other than those eligibility criteria that preclude the subject from receiving anthracycline-based therapy/cytotoxic chemotherapy),
-
Has been exposed to/received any of the following prior therapies, treatments, or procedures within the specified timeframes:
- Major surgery within 4 weeks prior to the first dose of epcoritamab;
- Non-investigational antineoplastic agents (except anti-CD20 monoclonal antibodies) or any investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of epcoritamab;
- Autologous hematopoietic stem cell transplantation (HSCT), CAR-T, allogeneic stem cell transplantation, or solid organ transplantation;
- Live, attenuated vaccines within 30 days prior to initiation of epcoritamab;
- Investigational vaccines within 28 days before the planned first dose of epcoritamab (ie, experimental and/or non-authorized SARS-CoV-2 vaccinations and therapies are not allowed);
- Invasive investigational medical device use within 28 days before the planned first dose of epcoritamab.
-
Has primary central nervous system (CNS) tumor or known CNS involvement or intracranial involvement as confirmed by mandatory brain magnetic resonance imaging/computed tomography (MRI/CT) scan at screening and, if clinically indicated, by lumbar puncture.
-
Has a seizure disorder requiring anti-epileptic therapy or experienced a seizure within 6 months of signing an informed consent form.
-
Has known past or current malignancy other than inclusion diagnosis, with exceptions as stated in protocol.
-
Has known or suspected allergies, hypersensitivity, or intolerance to either of the trial treatments or has known or suspected contraindication to the use of all locally available anti-cytokine therapies per local guidelines for management of cytokine release syndrome (CRS).
-
Has active hepatitis B virus (HBV) (DNA polymerase chain reaction [PCR]-positive) or hepatitis C virus (HCV) (RNA PCR-positive) infection, current alcohol abuse, or cirrhosis.
-
Has active cytomegalovirus (CMV) infection (DNA PCR-positive) requiring treatment.
-
Has suspected active or inadequately treated latent tuberculosis.
-
Has a known history of seropositivity for HIV. Note: HIV testing is required at screening only if required per local health authorities or institutional standards.
Note: Other protocol defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Epcoritamab in combination with lenalidomide Epcoritamab - Epcoritamab in combination with lenalidomide Lenalidomide - Epcoritamab monotherapy Epcoritamab -
- Primary Outcome Measures
Name Time Method Complete Response (CR) rate From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years Percentage of participants achieving CR. Assessed by the Investigator per Lugano criteria
- Secondary Outcome Measures
Name Time Method Duration of response (DOR) From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years Defined as the time between date of first response to the date of first documented tumor progression or death (due to any cause) whichever occurs first
Progression-free survival (PFS) From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years Defined as the time from first dose to date of PD or death (due to any cause) whichever occurs first
Incidence of clinically significant shifts in laboratory parameters From screening until end of the safety follow-up period (60 days after last dose) Clinical laboratory parameters assessed: hematology, chemistry, coagulation, tumor lysis, cardiac enzymes, immunoglobulins, and urinalyses
Duration of complete response (DOCR) From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years Defined as the time between the date of first CR to the date of the first documented tumor progression or death due to any cause, whichever comes first
Overall Response Rate (ORR) From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years Defined as the percentage of patients who achieve best overall response of complete response (CR) or partial response (PR) determined by Lugano criteria
Time to next anti-lymphoma therapy (TTNT) From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years Defined as the time from first dose to administration of subsequent anti-lymphoma therapy
Overall survival (OS) From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 3 years Defined at the timeframe from first dose to death
Time to response (TTR) From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 1 year Defined as the time from first dose to first documentation of objective tumor response (CR or PR)
Rate of minimal residual disease (MRD) negativity From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years Percentage of participants with at least 1 post-screening MRD negative result
Incidence and severity of adverse events (AEs) From screening until end of the safety follow-up period (60 days after last dose) An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment
Incidence of anti-drug antibodies (ADAs) to epcoritamab in plasma From first dose until treatment discontinuation (assessed up to 12 months) To evaluate immunogenicity
Evaluate patient-reported outcomes (PROs) related to lymphoma symptoms From cycle 1, day 1 until 90 days after last dose (each cycle is 28 days) Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym). Scale from 0-168 obtained by summing individual subscale scores. Higher scores for the scales indicate better quality of life
Assess pharmacokinetics (PK) of epcoritamab From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months) Terminal Elimination Half-Life (t 1/2)
Trial Locations
- Locations (78)
LKH - Universitätsklinikum der PMU Salzburg
🇦🇹Salzburg, Austria
UZ Leuven
🇧🇪Leuven, Belgium
Fondazione del Piemonte per l'Oncologia IRCC Candiolo
🇮🇹Candiolo, Italy
ICO l'Hospitalet - Hospital Duran i Reynals
🇪🇸Barcelona, Spain
UW Cancer Center at ProHealth Care
🇺🇸Waukesha, Wisconsin, United States
Vitaz
🇧🇪Temse, Belgium
AZ Turnhout - Campus Sint-Elisabeth
🇧🇪Turnhout, Belgium
Kepler Universitätsklinikum
🇦🇹Linz, Austria
Klinikum Wels-Grieskirchen GmbH
🇦🇹Wels, Austria
Institut Jules Bordet
🇧🇪Anderlecht, Belgium
GZA Ziekenhuizen
🇧🇪Antwerpen, Belgium
ZNA
🇧🇪Antwerpen, Belgium
UZ Brussels
🇧🇪Jette, Belgium
AZ Delta
🇧🇪Roeselare, Belgium
Fakultni nemocnice Hradec Kralove
🇨🇿Hradec Králové, Czechia
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
CHU Angers - Hôpital Hôtel Dieu
🇫🇷Angers, France
Hôpital Henri Mondor
🇫🇷Créteil, France
Hopital Claude Huriez - CHRU Lille
🇫🇷Lille, France
Hopital de la Conception - APHM
🇫🇷Marseille, France
CHU de Nantes - Hotel Dieu
🇫🇷Nantes, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Hôpital Saint-Antoine
🇫🇷Paris, France
Hôpital Saint-Louis
🇫🇷Paris, France
CHU de Bordeaux - Hôpital Haut-Lévêque
🇫🇷Pessac, France
CHU Amiens - Hopital Sud
🇫🇷Salouël, France
CHU Tours - Hôpital Bretonneau
🇫🇷Tours, France
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Baden Wuerttemberg, Germany
Universitaetsklinikum Aachen AOeR
🇩🇪Aachen, Germany
Vivantes Klinikum Neukoelln
🇩🇪Berlin, Germany
Universitaetsklinikum Wuerzburg
🇩🇪Würzburg, Germany
Clinica di Ematologia AOU Ospedali Riuniti di Ancona
🇮🇹Ancona, Italy
IRCCS Centro di Riferimento Oncologico
🇮🇹Aviano, Italy
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
🇮🇹Bologna, Italy
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
🇮🇹Brescia, Italy
IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST
🇮🇹Meldola, Italy
IEO Istituto Europeo di Oncologia Parent
🇮🇹Milano, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Ospedaliera Vincenzo Cervello
🇮🇹Palermo, Italy
AUSL Piacenza Ospedale Guglielmo da Saliceto
🇮🇹Piacenza, Italy
Azienda sanitaria integrata università di Trieste
🇮🇹Trieste, Italy
Kyushu University Hospital
🇯🇵Fukuoka shi, Japan
Kagoshima University Hospital
🇯🇵Kagoshima, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Japan
Cancer Institute Hospital of JFCR
🇯🇵Koto-Ku, Japan
Matsuyama Red Cross Hospital
🇯🇵Matsuyama, Japan
NHO Nagoya Medical Center
🇯🇵Nagoya shi, Japan
Yamagata University Hospital
🇯🇵Yamagata, Japan
Kindai University Hospital
🇯🇵Ōsaka-sayama, Japan
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Jeonbuk National University Hospital
🇰🇷Jeonju, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
🇵🇱Biała Podlaska, Poland
Pratia MCM Krakow
🇵🇱Kraków, Poland
Centrum Medyczne Pratia Poznan
🇵🇱Skorzewo, Poland
MICS Centrum Medyczne Torun
🇵🇱Toruń, Poland
ICO Badalona - Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital San Pedro de Alcantara
🇪🇸Cáceres, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Nuestra Señora de Valme
🇪🇸Sevilla, Spain
Hospital Universitario Puerta del Mar
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
Royal Marsden Hospital - Fulham
🇬🇧London, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Royal Cornwall Hospital NHS Trust
🇬🇧Truro, United Kingdom