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 (EPCORE™FL-2)

Genmab

Status and phase: Enrolling; Phase 3

Conditions: Follicular Lymphoma (FL)

Treatments: Drug: Obinutuzumab; Drug: Rituximab; Drug: Doxorubicin; Drug: Prednisone; Drug: Cyclophosphamide; Drug: Lenalidomide; Drug: Epcoritamab; Drug: Bendamustine; Drug: Vincristine

Study type: Interventional

Funder types: Industry

Identifiers

NCT06191744

2023-506906-38-00 (Other Identifier)

M22-003

Details and patient eligibility

About

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.

Enrollment: 1,080 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,080 participants in 4 patient groups

Arm A: Epcoritamab + Lenalidomide and Rituximab (R2)

Experimental group

Description:

Participants will receive epcoritamab in combination with R2 during the 120 week treatment duration.

Treatment:

Drug: Epcoritamab

Drug: Lenalidomide

Drug: Rituximab

Arm B: Chemoimmunotherapy (CIT) Option A

Experimental group

Description:

Participants will receive CIT Option A (obinutuzumab (G) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) \[G-CHOP\]/ rituximab (R)-CHOP during the 120 week treatment duration.

Treatment:

Drug: Vincristine

Drug: Cyclophosphamide

Drug: Prednisone

Drug: Doxorubicin

Drug: Obinutuzumab

Drug: Rituximab

Arm B: Chemoimmunotherapy (CIT) Option B

Experimental group

Description:

Participants will receive CIT Option B (G and bendamustine (Benda) \[G-Benda\]/R-Benda during the 120 week treatment duration.

Treatment:

Drug: Bendamustine

Drug: Prednisone

Drug: Obinutuzumab

Drug: Rituximab

Arm C: Lenalidomide and Rituximab (R2)

Experimental group

Description:

Participants will receive lenalidomide and rituximab (R2) during the 120 week treatment duration.

Treatment:

Drug: Lenalidomide

Drug: Rituximab