Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Previously Untreated Follicular Lymphoma

Follicular Lymphoma (FL) Clinical Trial

— EPCORE™FL-2  

Official title:

A Phase 3, Multicenter, Randomized, Open-Label Trial to Evaluate the Safety and Efficacy of Epcoritamab + Rituximab and Lenalidomide (R2) Compared to Chemoimmunotherapy in Previously Untreated Follicular Lymphoma (EPCORE™FL-2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06191744
• Other study ID #: M22-003
• Secondary ID: 2023-506906-38-0
• Status: Recruiting
• Phase: Phase 3
• Start date: February 5, 2024
• Est. completion date: May 18, 2037

Study information

• Verified date: June 2024
• Source: Genmab
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Follicular lymphoma (FL) is the second most common B-cell cancer and the most common type of cancer of lymphocytes. Unfortunately, this disease is incurable with conventional treatment and the disease recurs in almost all patients. This study will assess how safe and effective epcoritamab is in combination with lenalidomide and rituximab (R2) in treating adult participants with previously untreated FL. Adverse events and change in disease condition will be assessed.

Epcoritamab is an investigational drug being developed for the treatment of FL. Study doctors put the participants in 1 of 4 groups, called treatment arms. Each group receives a different treatment. Around 1080 adult participants with previously untreated FL will be enrolled in approximately 250 sites across the world.

Participants will receive R2 (intravenous [IV] infusion of rituximab (R) and oral capsules of lenalidomide) alone or in combination with subcutaneous injections of epcoritamab. Participants may also receive investigator's choice chemoimmunotherapy (CIT): IV infusion of obinutuzumab (G) and IV injections of cyclophosphamide, IV injections of doxorubicin, IV injections of vincristine, oral tablets of prednisone (CHOP) [G-CHOP]/ R-CHOP or G and IV infusion of bendamustine (Benda) [G-Benda]/R-Benda. The total treatment duration will be 120 weeks.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1080
• Est. completion date: May 18, 2037
• Est. primary completion date: May 18, 2037
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of follicular lymphoma (FL).

• Have CD20+, histologically confirmed classic FL (previously Grade 1 to 3a FL) at most recent representative tumor biopsy based on the local pathology report, according to the 5th edition of World Health Organization (WHO) Classification of Haematolymphoid Tumours.

• Are willing and able to comply with procedures required in the protocol.

• Must have stage, II, III or IV disease.

• Must be in need of systemic treatment per investigator, as evidenced by meeting at least one of the Groupe d'Etude des Lymphomes Folliculaire (GELF) criteria.

• Has one or more target lesions:

• A positron emission tomography (PET)/computerized tomography (CT) scan demonstrating PET-positive lesion(s), and

• >=1 measurable nodal lesion (long axis >1.5cm) or >=1 measurable extra-nodal lesion (long axis >1.0 cm) on CT scan or MRI

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

• Able to receive at least one of the standard of care chemoimmunotherapy (CIT) treatment regimens: [Arm B] at the discretion of the Investigator, and rituximab and lenalidomide (R2) [Arm C].

• Have laboratory values meeting the criteria in the protocol.

Exclusion Criteria:

• Had major surgery within 4 weeks prior to randomization.

• Have active cytomegalovirus (CMV) disease.

Related Conditions & MeSH terms

• Follicular Lymphoma (FL)
• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• Epcoritamab
Subcutaneous (SC) Injection
• Prednisone
Oral Tablet
• Rituximab
Intravenous (IV) Infusion
• Lenalidomide
Oral Capsule
• Doxorubicin
IV Injection
• Vincristine
IV Injection
• Cyclophosphamide
IV Injection
• Obinutuzumab
IV Infusion
• Bendamustine
IV Infusion

Locations

Country	Name	City	State
Australia	Townsville University Hospital /ID# 259323	Douglas	Queensland
Australia	Peter MacCallum Cancer Center /ID# 260431	Melbourne	New South Wales
Australia	Royal Perth Hospital /ID# 259319	Perth	Western Australia
Australia	Westmead Hospital /ID# 261465	Westmead	New South Wales
Israel	HaEmek Medical Center /ID# 259936	Afula	H_efa
Israel	Soroka University Medical Center /ID# 259937	Be'er Sheva	HaDarom
Israel	Hadassah /ID# 259935	Jerusalem	Yerushalayim
Israel	Meir Medical Center /ID# 259938	Kfar Saba	HaMerkaz
Israel	Tel Aviv Sourasky Medical Center /ID# 259933	Tel Aviv	Tel-Aviv
Korea, Republic of	Seoul National University Bundang Hospital /ID# 260009	Seongnam-si	Gyeonggido
Korea, Republic of	Asan Medical Center /ID# 260010	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Samsung Medical Center /ID# 260008	Seoul
Korea, Republic of	Seoul National University Hospital /ID# 260007	Seoul
Puerto Rico	Pan American Center for Oncology Trials, LLC /ID# 260265	Rio Piedras
Romania	Fundeni Clinical Institute /ID# 260296	Bucharest	Bucuresti
Romania	Spitalul Clinic Coltea /ID# 259699	Bucharest
Serbia	Clinical Hospital Center Zvezdara /ID# 260900	Belgrade
Serbia	University Clinical Center Vojvodina /ID# 259272	Novi Sad
Spain	Hospital Santa Creu i Sant Pau /ID# 260498	Barcelona
Spain	CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 261512	Madrid
Taiwan	China Medical University Hospital /ID# 260357	Taichung
Taiwan	Taichung Veterans General Hospital /ID# 260361	Taichung
Taiwan	National Cheng Kung University Hospital /ID# 260363	Tainan
Taiwan	National Taiwan University Hospital /ID# 260341	Taipei City	Taipei
United States	American Oncology Partners of Maryland /ID# 259476	Bethesda	Maryland
United States	Intermountain Health - St Vincent Regional Hospital - Cancer Centers of Montana /ID# 260006	Billings	Montana
United States	St. Luke's Hospital - Chesterfield /ID# 260489	Chesterfield	Missouri
United States	Mission Cancer and Blood /ID# 262132	Des Moines	Iowa
United States	Fort Wayne Medical Oncology and Hematology- South Office /ID# 259583	Fort Wayne	Indiana
United States	Prisma Health /ID# 259602	Greenville	South Carolina
United States	Cancer Specialists of North Florida /ID# 262445	Jacksonville	Florida
United States	Norton Cancer Institute - St. Matthews /ID# 261076	Louisville	Kentucky
United States	Vista Oncology - East Olympia /ID# 261360	Olympia	Washington
United States	Advent Health /ID# 261578	Orlando	Florida
United States	Illinois Cancer Care, PC /ID# 261526	Peoria	Illinois
United States	Virginia Mason Hospital & Medical Center /ID# 260549	Seattle	Washington
United States	Toledo Clinic Cancer Center - Main /ID# 260488	Toledo	Ohio
United States	Clinical Research Alliance, Inc. /ID# 261078	Westbury	New York

Sponsors (2)

Lead Sponsor	Collaborator
Genmab	AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Israel,  Korea, Republic of,  Puerto Rico,  Romania,  Serbia,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Arm A vs Arm B: Percentage of Participants who Achieve Complete Response rate at 30 months (CR30)	CR30 will be determined by positron emission tomography-computerized tomography (cat scan) [PET-CT] per Lugano 2014 criteria, as assessed by independent review committee (IRC).	Up to 30 Months
Primary	Arm A vs Arm B: Number of Participants with Progression-free survival (PFS)	PFS is defined as the time from randomization until disease progression determined by Lugano 2014 criteria per IRC, or death, whichever occurs first.	Up to 10 Years
Secondary	Arm A vs Arm B: Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death of any cause.	Up to 10 Years
Secondary	Arm A vs Arm B: Rate of Minimal Residual Disease (MRD) Negativity Rate	MRD negativity rate, defined as the absence of tumor specific molecules in whole blood and/or bone marrow in participants with follicular lymphoma (FL) MRD at baseline.	Up to 10 Years
Secondary	Arm A vs Arm B: Percentage of Participants who Maintain Physical Functioning (PF) According to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer (EORTC QLQ-C30)	The PF of EORTC QLQ-C30 is a 5-item questionnaire to assess the physical function of the participant, with a higher score indication worse functioning.	25 Weeks
Secondary	Arm A vs Arm C: Percentage of Participants who Achieve CR30	CR30 will be determined by PET-CT per Lugano 2014 criteria, as assessed by IRC.	Up to 30 Months
Secondary	Arm A vs Arm C: Number of Participants with PFS	PFS is defined as the time from randomization until disease progression determined by Lugano 2014 criteria per IRC, or death, whichever occurs first.	Up to 10 Years
Secondary	Arm A vs Arm C: OS	OS is defined as the time from the date of randomization to the date of death of any cause.	Up to 10 Years
Secondary	Arm A vs Arm C: Rate of MRD Negativity	MRD negativity, defined as the absence of tumor specific molecules in whole blood and/or bone marrow in participants with FL MRD at baseline.	Up to 10 Years
Secondary	Arm A vs Arm C: Percentage of Participants who Maintain PF According to EORTC QLQ-C30	The PF of EORTC QLQ-C30 is a 5-item questionnaire to assess the physical function of the participant, with a higher score indication worse functioning.	Up to 10 Years
Secondary	Arm A vs Arm B: Percentage of Participants who Achieve CR30	CR30 will be determined by PET-CT per Lugano 2014 criteria, as assessed by investigator.	Up to 30 Months
Secondary	Arm A vs Arm C: Percentage of Participants who Achieve CR30	CR30 will be determined by PET-CT per Lugano 2014 criteria, as assessed by investigator.	Up to 30 Months
Secondary	Arm A vs Arm C: Number of Participants with PFS	PFS is defined as the time from randomization until disease progression determined by Lugano 2014 criteria per investigator, or death, whichever occurs first.	Up to 10 Years
Secondary	Arm A vs Arm B: Percentage of Participants with Change in CR Rate per IRC	CR will be determined by PET-CT per Lugano 2014 criteria, as assessed by IRC.	Up to 10 Years
Secondary	Arm A vs Arm C: Percentage of Participants with Change in CR Rate per IRC	CR will be determined by PET-CT per Lugano 2014 criteria, as assessed by IRC.	Up to 10 Years
Secondary	Arm A vs Arm B: Percentage of Participants with Change in CR Rate per Investigator	CR will be determined by PET-CT per Lugano 2014 criteria, as assessed by investigator.	Up to 10 Years
Secondary	Arm A vs Arm C: Percentage of Participants with Change in CR Rate per Investigator	CR will be determined by PET-CT per Lugano 2014 criteria, as assessed by investigator.	Up to 10 Years
Secondary	Arm A vs Arm B: Number of Participants with Best Overall Response (BOR) per per Investigator	BOR is defined as the percentage of participants who achieve CR or partial response (PR) determined by Lugano 2014 criteria as assessed by investigator, or death from any cause.	Up to 10 Years
Secondary	Arm A vs Arm C: Number of Participants with BOR per Investigator	BOR is defined as the percentage of participants who achieve CR or PR determined by Lugano 2014 criteria as assessed by investigator, or death from any cause.	Up to 10 Years
Secondary	Arm A vs Arm B: Number of Participants with BOR per IRC	BOR is defined as the percentage of participants who achieve CR or PR determined by Lugano 2014 criteria as assessed by IRC, or death from any cause.	Up to 10 Years
Secondary	Arm A vs Arm C: Number of Participants with BOR per IRC	BOR is defined as the percentage of participants who achieve CR or PR determined by Lugano 2014 criteria as assessed by IRC, or death from any cause.	Up to 10 Years
Secondary	Arm A vs Arm B: Number of Participants with Event-free Survival (EFS) per IRC	EFS is defined as the time from randomization until adverse event determined by Lugano 2014 criteria per IRC, or death, whichever occurs first.	Up to 10 Years
Secondary	Arm A vs Arm C: Number of Participants with EFS per IRC	EFS is defined as the time from randomization until adverse event determined by Lugano 2014 criteria per IRC, or death, whichever occurs first.	Up to 10 Years
Secondary	Arm A vs Arm B: Number of Participants with EFS per Investigator	EFS is defined as the time from randomization until adverse event determined by Lugano 2014 criteria per investigator, or death, whichever occurs first.	Up to 10 Years
Secondary	Arm A vs Arm C: Number of Participants with EFS per Investigator	EFS is defined as the time from randomization until adverse event determined by Lugano 2014 criteria per investigator, or death, whichever occurs first.	Up to 10 Years
Secondary	Arm A vs Arm B: Duration of Response (DOR) per IRC	DOR is defined as the time from PR or CR to disease progression per Lugano 2014 criteria, as assessed by IRC.	Up to 10 Years
Secondary	Arm A vs Arm C: DOR per IRC	DOR is defined as the time from PR or CR to disease progression per Lugano 2014 criteria, as assessed by IRC.	Up to 10 Years
Secondary	Arm A vs Arm B: DOR per Investigator	DOR is defined as the time from PR or CR to disease progression per Lugano 2014 criteria, as assessed by investigator.	Up to 10 Years
Secondary	Arm A vs Arm C: DOR per Investigator	DOR is defined as the time from PR or CR to disease progression per Lugano 2014 criteria, as assessed by investigator.	Up to 10 Years
Secondary	Arm A vs Arm B: Duration of Complete Response (DOCR) per IRC	DOCR is defined as the time from CR to disease progression per Lugano 2014 criteria, as assessed by IRC.	Up to 10 Years
Secondary	Arm A vs Arm C: DOCR per IRC	DOCR is defined as the time from CR to disease progression per Lugano 2014 criteria, as assessed by IRC.	Up to 10 Years
Secondary	Arm A vs Arm B: DOCR per Investigator	DOCR is defined as the time from CR to disease progression per Lugano 2014 criteria, as assessed by investigator.	Up to 10 Years
Secondary	Arm A vs Arm C: DOCR per Investigator	DOCR is defined as the time from CR to disease progression per Lugano 2014 criteria, as assessed by investigator.	Up to 10 Years
Secondary	Arm A vs Arm B: Time to Next Anti-lymphoma Therapy (TTNT)	TTNT is defined as the time from randomization to first documented administration of subsequent anti-lymphoma therapy	Up to 10 Years
Secondary	Arm A vs Arm C: TTNT	TTNT is defined as the time from randomization to first documented administration of subsequent anti-lymphoma therapy	Up to 10 Years
Secondary	Arm A vs Arm B: Time to Progression per IRC	Time to progression defined as the time from randomization to disease progression per Lugano 2014 criteria, as assessed by IRC.	Up to 10 Years
Secondary	Arm A vs Arm C: Time to Progression per IRC	Time to progression defined as the time from randomization to disease progression per Lugano 2014 criteria, as assessed by IRC.	Up to 10 Years
Secondary	Arm A vs Arm B: Time to Progression per Investigator	Time to progression defined as the time from randomization to disease progression per Lugano 2014 criteria, as assessed by investigator.	Up to 10 Years
Secondary	Arm A vs Arm C: Time to Progression per Investigator	Time to progression defined as the time from randomization to disease progression per Lugano 2014 criteria, as assessed by investigator.	Up to 10 Years
Secondary	Arm A vs Arm B: Number of Participants with Progression-free Survival After Subsequent Anti-Lymphoma Therapy (PFS2)	PFS2 is defined as the time after subsequent anti-lymphoma therapy to the earliest occurrence of disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause.	Up to 10 Years
Secondary	Arm A vs Arm C: Number of Participants with PFS2	PFS2 is defined as the time after subsequent anti-lymphoma therapy to the earliest occurrence of disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause.	Up to 10 Years
Secondary	Arm A vs Arm B: Change in Tolerability as Measured by Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE)	The PRO-CTCAE is a patient-reported outcome measurement system developed to assess symptomatic toxicity in participants in cancer clinical trials. PRO-CTCAE items evaluate common symptoms from study treatment on their frequency, severity, interference, amount, presence/absence.	Up to 10 Years
Secondary	Arm A vs Arm C: Change in Tolerability as Measured by PRO-CTCAE	The PRO-CTCAE is a patient-reported outcome measurement system developed to assess symptomatic toxicity in participants in cancer clinical trials. PRO-CTCAE items evaluate common symptoms from study treatment on their frequency, severity, interference, amount, presence/absence.	Up to 10 Years
Secondary	Arm A vs Arm B: Change in Tolerability as Measured by The Functional Assessment of Cancer Therapy Singly Item - GP5 (FACT-GP5)	The FACT-GP5 is a single question asking if participant is bothered by side effects of treatment.	Up to 10 Years
Secondary	Arm A vs Arm C: Change in Tolerability as Measured by FACT-GP5	The FACT-GP5 is a single question asking if participant is bothered by side effects of treatment.	Up to 10 Years
Secondary	Arm A vs Arm B: Change in Symptoms as Measured by The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)	The objective of the FACT-Lym patient reported outcome (PRO) is to assess health-related quality of life issues for adult lymphoma patients. It utilizes a 5-point Likert-type scale.	Up to 10 Years
Secondary	Arm A vs Arm C: Change in Symptoms as Measured by FACT-Lym	The objective of the FACT-Lym patient reported outcome (PRO) is to assess health-related quality of life issues for adult lymphoma patients. It utilizes a 5-point Likert-type scale.	Up to 10 Years
Secondary	Arm A vs Arm B: Change in Quality of Life (QoL) as Measured by FACT-Lym	The objective of the FACT-Lym PRO is to assess health-related quality of life issues for adult lymphoma patients. It utilizes a 5-point Likert-type scale.	Up to 10 Years
Secondary	Arm A vs Arm C: Change in QoL as Measured by FACT-Lym	The objective of the FACT-Lym PRO is to assess health-related quality of life issues for adult lymphoma patients. It utilizes a 5-point Likert-type scale.	Up to 10 Years
Secondary	Arm A vs Arm B: Change in QoL as Measured by 5-Level European Quality of Life (EuroQol)-5-dimension [EQ-5D-5L]	The EQ-5D-5L is a standardized, non-disease specific instrument used to measure health-related quality of life. The EQ-5D-5L assesses general health on 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems). The scores for the 5 dimensions are used to compute a single utility index score ranging from 0 to 1 representing the general health status of the individual, with higher scores indicating better health state.	Up to 10 Years
Secondary	Arm A vs Arm C: Change in QoL as Measured by EQ-5D-5L	The EQ-5D-5L is a standardized, non-disease specific instrument used to measure health-related quality of life. The EQ-5D-5L assesses general health on 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems). The scores for the 5 dimensions are used to compute a single utility index score ranging from 0 to 1 representing the general health status of the individual, with higher scores indicating better health state.	Up to 10 Years
Secondary	Arm A vs Arm B: Change in Participant Belief in in Efficacy of Treatment as Measured by Patient Global Impression of Change (PGIC)	The self-report measure PGIC reflects a participant's belief about the efficacy of treatment. The PGIC is a 7-point scale depicting a participant's rating of overall improvement since start of treatment. Participants rate their change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.	Up to 10 Years
Secondary	Arm A vs Arm C: Change in Participant Belief in in Efficacy of Treatment as Measured by PGIC	The self-report measure PGIC reflects a participant's belief about the efficacy of treatment. The PGIC is a 7-point scale depicting a participant's rating of overall improvement since start of treatment. Participants rate their change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.	Up to 10 Years
Secondary	Arm A vs Arm B: Change in Participant Belief in in Efficacy of Treatment as Measured by Patient Global Impression of Severity (PGIS)	The self-report measure PGIS reflects a participant's belief about their lymphoma symptoms over the past 7 days. The PGIS is a 5-point scale depicting a participant's rating of overall severity.	Up to 10 Years
Secondary	Arm A vs Arm C: Change in Participant Belief in in Efficacy of Treatment as Measured by PGIS	The self-report measure PGIS reflects a participant's belief about their lymphoma symptoms over the past 7 days. The PGIS is a 5-point scale depicting a participant's rating of overall severity.	Up to 10 Years

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