Subcutaneous Epcoritamab With or Without Lenalidomide as First Line Therapy for Diffuse Large B-Cell Lymphoma

Diffuse Large B-Cell Lymphoma Clinical Trial

— EPCORE DLBCL-3  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05660967
• Other study ID #: GCT3013-06
• Secondary ID: 2021-005744-29jR
• Status: Recruiting
• Phase: Phase 2
• Start date: March 6, 2023
• Est. completion date: March 2027

Study information

• Verified date: June 2024
• Source: Genmab
• Contact: Genmab Trial Information
• Phone: +4570202728
• Email: clinicaltrials[@]genmab.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: March 2027
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 75 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Biological:
• Epcoritamab
Epcoritamab will be administered by subcutaneous (SC) injections in 28-day cycles for up to 12 cycles.

Drug:
• Lenalidomide
Lenalidomide will be administered orally (capsules; starting dose of 10 or 20 mg) once daily on Day 1 to Day 21 of each 28-day cycle for up to 12 cycles.

Locations

Country	Name	City	State
Austria	Kepler Universitätsklinikum	Linz
Austria	LKH - Universitätsklinikum der PMU Salzburg	Salzburg
Austria	Klinikum Wels-Grieskirchen GmbH	Wels
Belgium	GZA Ziekenhuizen	Antwerp
Belgium	ZNA	Antwerpen
Belgium	Institut Jules Bordet	Brussel
Belgium	Universitair Ziekenhuis Brussel	Brussel
Belgium	UZ Leuven	Leuven
Belgium	AZ Delta	Roeselare
Belgium	Vitaz	Sint-Niklaas
Belgium	AZ Turnhout - Campus Sint-Elisabeth	Turnhout
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Králové
Czechia	Vseobecna fakultni nemocnice v Praze	Prague
Czechia	Fakultni nemocnice v Motole	Praha
France	CHU de Bordeaux - Hôpital Haut-Lévêque	Bordeaux
France	CHU Amiens - Hopital Sud	Lille
France	Hopital Claude Huriez - CHRU Lille	Lille
France	Hopital de la Conception - APHM	Marseille
France	CHU Angers - Hôpital Hôtel Dieu	Nantes
France	CHU de Nantes - Hotel Dieu	Nantes
France	CHU Tours - Hôpital Bretonneau	Nantes
France	Centre Antoine Lacassagne	Nice
France	Hôpital Henri Mondor	Paris
France	Hôpital Saint-Antoine	Paris
France	Hôpital Saint-Louis	Paris
Germany	Universitaetsklinikum Aachen AOeR	Aachen
Germany	Vivantes Klinikum Neukoelln	Berlin
Germany	Universitaetsklinikum Freiburg	Freiburg	Baden Wuerttemberg
Germany	Universitaetsklinikum Wuerzburg	Würzburg
Italy	Clinica di Ematologia AOU Ospedali Riuniti di Ancona	Ancona
Italy	IRCCS Centro di Riferimento Oncologico	Aviano
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)	Brescia
Italy	Fondazione del Piemonte per l'Oncologia IRCC Candiolo	Candiolo
Italy	IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura 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
Japan	Kyushu University Hospital	Fukuoka
Japan	Kagoshima University Hospital	Kagoshima
Japan	Kanazawa University Hospital	Kanazawa
Japan	Matsuyama Red Cross Hospital	Matsuyama
Japan	Kindai University Hospital	Osaka
Japan	Cancer Institute Hospital of JFCR	Tokyo
Japan	Yamagata University Hospital	Yamagata
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Jeonbuk National University Hospital	Jeonju	North Jeolla
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	National Cancer Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	KO-MED Centra Kliniczne Biala Podlaska	Biala Podlaska
Poland	Pratia MCM	Kraków
Poland	Centrum Medyczne Pratia	Poznan
Poland	MICS Centrum Medyczne	Torun
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	ICO Badalona - Hospital Universitari Germans Trias i Pujol	Barcelona
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	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
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Royal Marsden Hospital - Fulham	Fulham
United Kingdom	Churchill Hospital	London
United Kingdom	Royal Marsden Hospital	London
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Royal Cornwall Hospital	Truro
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	AbbVie

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Czechia,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response (CR) rate	Percentage of participants achieving CR. Assessed by the Investigator per Lugano criteria	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Secondary	Duration of response (DOR)	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	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Secondary	Duration of complete response (DOCR)	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	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Secondary	Time to response (TTR)	Defined as the time from first dose to first documentation of objective tumor response (CR or PR)	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 1 year
Secondary	Overall Response Rate (ORR)	Defined as the percentage of patients who achieve best overall response of complete response (CR) or partial response (PR) determined by Lugano criteria	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Secondary	Progression-free survival (PFS)	Defined as the time from first dose to date of PD or death (due to any cause) whichever occurs first	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Secondary	Time to next anti-lymphoma therapy (TTNT)	Defined as the time from first dose to administration of subsequent anti-lymphoma therapy	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Secondary	Rate of minimal residual disease (MRD) negativity	Percentage of participants with at least 1 post-screening MRD negative result	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 2 years
Secondary	Overall survival (OS)	Defined at the timeframe from first dose to death	From randomization (for patients enrolled in stage 1) or from first dose (for patients enrolled in stage 2) and up to 3 years
Secondary	Incidence and severity of adverse events (AEs)	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	From screening until end of the safety follow-up period (60 days after last dose)
Secondary	Incidence of clinically significant shifts in laboratory parameters	Clinical laboratory parameters assessed: hematology, chemistry, coagulation, tumor lysis, cardiac enzymes, immunoglobulins, and urinalyses	From screening until end of the safety follow-up period (60 days after last dose)
Secondary	Incidence of anti-drug antibodies (ADAs) to epcoritamab in plasma	To evaluate immunogenicity	From first dose until treatment discontinuation (assessed up to 12 months)
Secondary	Evaluate patient-reported outcomes (PROs) related to lymphoma symptoms	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	From cycle 1, day 1 until 90 days after last dose (each cycle is 28 days)
Secondary	Assess pharmacokinetics (PK) of epcoritamab	Total body clearance of drug from the plasma (CL)	From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)
Secondary	Assess pharmacokinetics (PK) of epcoritamab	Maximum observed concentration (Cmax)	From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)
Secondary	Assess pharmacokinetics (PK) of epcoritamab	Time to reach Cmax (Tmax)	From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)
Secondary	Assess pharmacokinetics (PK) of epcoritamab	Terminal Elimination Half-Life (t 1/2)	From first dose and at multiple time points until treatment discontinuation (assessed up to 12 months)