Clinical trial NCT05660967: Subcutaneous Epcoritamab With or Without Lenalidomide as First Line Therapy for Diffuse Large B-Cell Lymphoma
Official title: Efficacy and Safety of Epcoritamab Monotherapy and in Combination With Lenalidomide as First-line Therapy for Anthracycline-ineligible Diffuse Large B-Cell Lymphoma Patients, an Open-label, Randomized, Multicenter, Global Phase 2 Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Keywords: Double-hit lymphoma
Triple-hit lymphoma
Follicular grade 3B
T-cell/histiocyte rich LBCL
DuoBody®
Anti-CD3
Anti-CD20
Subcutaneous
Bispecific antibody
EPCORE
Lead sponsor: Genmab
Sponsor class: INDUSTRY
Collaborators: name: AbbVie
First posted: 2022-12-21
Enrollment: 180
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Complete Response (CR) rate
timeFrame: From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Secondary outcomes:
measure: Duration of response (DOR)
timeFrame: From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
measure: Duration of complete response (DOCR)
timeFrame: From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
measure: Time to response (TTR)
timeFrame: From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 1 year
measure: Overall Response Rate (ORR)
timeFrame: From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
measure: Progression-free survival (PFS)
timeFrame: From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
measure: Time to next anti-lymphoma therapy (TTNT)
timeFrame: From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
measure: Rate of minimal residual disease (MRD) negativity
timeFrame: From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
measure: Overall survival (OS)
timeFrame: From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 3 years
measure: Incidence and severity of adverse events (AEs)
timeFrame: From screening until end of the safety follow-up period (60 days after last dose)
measure: Incidence of clinically significant shifts in laboratory parameters
timeFrame: From screening until end of the safety follow-up period (60 days after last dose)
measure: Incidence of anti-drug antibodies (ADAs) to epcoritamab in plasma
timeFrame: From first dose until treatment discontinuation (assessed up to 12 months)
measure: Evaluate patient-reported outcomes (PROs) related to lymphoma symptoms
timeFrame: From cycle 1, day 1 until 90 days after last dose (each cycle is 28 days)
measure: Assess pharmacokinetics (PK) of epcoritamab
timeFrame: From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)
measure: Assess pharmacokinetics (PK) of epcoritamab
timeFrame: From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)
measure: Assess pharmacokinetics (PK) of epcoritamab
timeFrame: From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)
measure: Assess pharmacokinetics (PK) of epcoritamab
timeFrame: From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)
Other outcomes:
Locations:
city: Waukesha
country: United States
facility: UW Cancer Center at ProHealth Care
state: Wisconsin
city: Linz
country: Austria
facility: Kepler Universitätsklinikum
city: Salzburg
country: Austria
facility: LKH - Universitätsklinikum der PMU Salzburg
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Antwerpen
country: Belgium
facility: GZA Ziekenhuizen
city: Antwerpen
country: Belgium
facility: ZNA
city: Jette
country: Belgium
facility: UZ Brussels
city: Leuven
country: Belgium
facility: UZ Leuven
city: Roeselare
country: Belgium
facility: AZ Delta
city: Temse
country: Belgium
facility: Vitaz
city: Turnhout
country: Belgium
facility: AZ Turnhout - Campus Sint-Elisabeth
city: Hradec Králové
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Angers
country: France
facility: CHU Angers - Hôpital Hôtel Dieu
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Lille
country: France
facility: Hopital Claude Huriez - CHRU Lille
city: Marseille
country: France
facility: Hopital de la Conception - APHM
city: Nantes
country: France
facility: CHU de Nantes - Hotel Dieu
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Pessac
country: France
facility: CHU de Bordeaux - Hôpital Haut-Lévêque
city: Salouël
country: France
facility: CHU Amiens - Hopital Sud
city: Tours
country: France
facility: CHU Tours - Hôpital Bretonneau
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
state: Baden Wuerttemberg
city: Aachen
country: Germany
facility: Universitaetsklinikum Aachen AOeR
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukoelln
city: Würzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Ancona
country: Italy
facility: Clinica di Ematologia AOU Ospedali Riuniti di Ancona
city: Aviano
country: Italy
facility: IRCCS Centro di Riferimento Oncologico
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia IRCC Candiolo
city: Meldola
country: Italy
facility: IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia Parent
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Palermo
country: Italy
facility: Azienda Ospedaliera Vincenzo Cervello
city: Piacenza
country: Italy
facility: AUSL Piacenza Ospedale Guglielmo da Saliceto
city: Trieste
country: Italy
facility: Azienda sanitaria integrata università di Trieste
city: Fukuoka shi
country: Japan
facility: Kyushu University Hospital
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Koto-Ku
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Matsuyama
country: Japan
facility: Matsuyama Red Cross Hospital
city: Nagoya shi
country: Japan
facility: NHO Nagoya Medical Center
city: Yamagata
country: Japan
facility: Yamagata University Hospital
city: Ōsaka-sayama
country: Japan
facility: Kindai University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Biała Podlaska
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
city: Kraków
country: Poland
facility: Pratia MCM Krakow
city: Skorzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Toruń
country: Poland
facility: MICS Centrum Medyczne Torun
city: Badalona
country: Spain
facility: ICO Badalona - Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitario Nuestra Señora de Valme
city: Sevilla
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: London
country: United Kingdom
facility: Royal Marsden Hospital - Fulham
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital NHS Trust
Study officials:
References: