A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL (EPCORE DLBCL-1)

Genmab

Status and phase: Active, not recruiting; Phase 3

Conditions: Diffuse Large B-cell Lymphoma

Treatments: Drug: Investigator's Choice Chemotherapy; Biological: Epcoritamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04628494

MOH_2021-01-18_009672 (Registry Identifier)

2020-003016-27 (EudraCT Number)

NL75079.056.20 (Registry Identifier)

286972 (Other Identifier)

CTR20221558 (Registry Identifier)

2023-504830-23-00 (Registry Identifier)

GCT3013-05

jRCT2021220017 (Registry Identifier)

Details and patient eligibility

About

The purpose of this trial is to find out if epcoritamab, also known as EPKINLY™ and GEN3013, is safe and works well as treatment for patients with diffuse large B-cell lymphoma (DLBCL) that are not responding to treatment, have grown in size, or have come back following treatment with at least 1 prior systemic cancer therapy. All participants in this trial will be randomly assigned to receive either epcoritamab or a pre-specified investigator's choice (standard of care) chemotherapy (either rituximab + gemcitabine + oxaliplatin [R-GemOx], or bendamustine + rituximab [BR]). Participants must have failed or be ineligible to receive an autologous stem cell transplant (ASCT).

Epcoritamab will be injected under the skin. Investigator's choice chemotherapy will be given intravenously.

Trial details include:

• The trial duration will be up to 5 years.

• All trial participants have a 21-day screening period, a treatment period, and a follow-up period that continues until death.

• The estimated trial duration for an individual subject depends upon the treatment arm assigned:

  • Participants who receive epcoritamab will have 28-day treatment cycles. Epcoritamab will be given once weekly for the first 3 months, then every other week for 6 months, then every 28 days until lymphoma progression or unacceptable adverse events.

  • Participants who receive investigator's choice (standard of care) chemotherapy will receive treatments either:

    • R-GemOx: On Day 1 (or Day 1 & Day 2), and Day 15 (or Day 15 & Day 16) every 28 days, for up to 4 months; or
    • BR: On Day 1 and Day 2 every 3 weeks for up to 4.5 months.

Full description

The trial is an open label, multi-center, global phase-3 randomized trial of epcoritamab. The goal of this randomized trial is to evaluate the efficacy of epcoritamab (GEN3013, DuoBody®-CD3xCD20) compared to investigator's choice of chemotherapy, in patients with relapsed, refractory DLBCL who have failed or are ineligible for high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT). No change in chemotherapy is permitted for participants during the treatment phase of the trial.

Enrollment: 552 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Main Inclusion Criteria:

1. Relapsed or refractory disease and previously treated with at least 1 line of systemic antineoplastic therapy including anti-CD20 mAb-containing combination chemotherapy since lymphoma diagnosis

2. One of the confirmed histologies below with CD20-positivity:

   1. DLBCL, NOS, including de novo or histologically transformed from FL
   2. "Double-hit" or "triple-hit" DLBCL (technically classified in WHO 2016 as HGBCL, with MYC and BCL2 and/or BCL6 translocations), including de novo or histologically transformed from FL
   3. FL Grade 3B
   4. T-cell/histiocyte-rich large B-cell lymphoma

3. ECOG PS score of 0-2

4. Failed previous HDT-ASCT or not eligible for HDT-ASCT at screening

5. Patients must have detectable disease by PET scan and measurable by CT scan or MRI

6. Acceptable renal and liver function

7. Life expectancy >2 months on SOC treatment

Main Exclusion Criteria:

1. Primary Central Nervous System (CNS) tumor or known CNS involvement
2. Any prior therapy with a bispecific antibody targeting CD3 and CD20
3. Major surgery within 4 weeks prior to randomization
4. Chemotherapy and other non-investigational antineoplastic agents (except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization
5. Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to randomization
6. ASCT within 100 days of randomization
7. Treatment with CAR-T therapy within 100 days prior to randomization
8. Seizure disorder requiring anti-epileptic therapy
9. Clinically significant cardiac disease

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

552 participants in 2 patient groups

Epcoritamab (GEN3013; DuoBody®CD3xCD20)

Experimental group

Description:

Epcoritamab will be administered in Cycles of 28 days until any of the discontinuation criteria is met

Treatment:

Biological: Epcoritamab

Investigator's choice of chemotherapy

Active Comparator group

Description:

R-GemOx will be administrated in Cycles of 28 days until maximum cycles completion or any of the discontinuation criteria is met BR will be administrated in Cycles of 21 days until maximum cycles completion or any of the discontinuation criteria is met

Treatment:

Drug: Investigator's Choice Chemotherapy