The Phase 1b/2, Open-Label Trial to Assess the Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Combination with Other Agents in Subjects with B-cell Non-Hodgkin Lymphoma

There is an unmet medical need for new efficacious therapies for patients with
B-cell non-Hodgkin lymphoma (B-NHL). Epcoritamab demonstrated a favorable
safety profile and overall response rate (ORR) in a monotherapy trial.
Combining epcoritamab with chemotherapeutic agents with different mechanisms of
action may improve efficacy with a low potential for overlapping toxicities

This study has been transitioned to CTIS with ID 2023-504805-35-00 check the CTIS register for the current data.

Dose Escalation Phase
Primary
- Evaluate the safety and tolerability of epcoritamab in combination with other
agents

Secondary
- Characterize the PK properties of epcoritamab
- To evaluate pharmacodynamic markers linked to efficacy and mechanism of
action of epcoritamab
- Evaluate immunogenicity
- Assess the preliminary anti-tumor activity of epcoritamab in combination with
other agents

Expansion Phase:
Arms 1-6 and 8-10: Assess the preliminary anti-tumor activity of epcoritamab in
combination with other agents
Arm 7: Evaluate the safety and tolerability of epcoritamab following standard
of care (SOC)

Secondary
- Further assess the preliminary anti-tumor activity of epcoritamab in
combination with other agents
- Further evaluate the safety and tolerability of epcoritamab in combination
with other agents
- Characterize the PK properties of Epcoritamab
- To evaluate pharmacodynamic markers linked to efficacy and mechanism of
action of epcoritamab
- Evaluate immunogenicity

This is a phase 1b/2, open-label, multinational, multicenter, interventional
trial to evaluate the safety, tolerability, PK, pharmacodynamics/biomarkers,
immunogenicity, and preliminary efficacy of epcoritamab in combination with
other standard of care (SOC) agents in subjects with B-NHL.

Epcoritamab (the investigational medicinal product [IMP]) will be administered
as a
subcutaneous injection. The schedules of administration are as follows:
Arm 1: epcoritamab + R-CHOP for 8 cycles (21-day cycles; 6 cycles of
epcoritamab in combination with SOC followed by 2 cycles of epcoritamab
monotherapy)
Arm 2: epcoritamab + rituximab + lenalidomide until progression (28-day cycles;
12 cycles of epcoritamab in combination with SOC followed by epcoritamab
monotherapy until progression or unacceptable toxicity)
Arm 3: epcoritamab + BR for 8 cycles (21-day cycles; 6 cycles in combination
with SOC followed by 2 cycles of epcoritamab monotherapy)
Arm 4: epcoritamab + R-DHAP until high-dose therapy with autologous stem cell
transplant (HDT-ASCT) (21-day cycles; 3 cycles of epcoritamab in combination
with SOC followed by epcoritamab monotherapy until conditioning for transplant)
Arm 5: epcoritamab + GemOx until progression (28-day cycles; 4 cycles in
combination with SOC followed by epcoritamab monotherapy until progression or
unacceptable toxicity)
Arm 6: epcoritamab + rituximab + lenalidomide, 12 cycles in combination
followed by epcoritamab monotherapy Q4W for total of 2 yrs.
Arm 7: epcoritamab maintenance, step-up dosing in C1, followed by Q8W for a
total of 2 yrs
Arm 8: epcoritamab + R- mini-CHOP for up to 6 cycles (21 day cycles) followed
by 2 cycles of epcoritamab (28 day cycles)

Subjects will need to follow appointments for visits. They will have physical
examinations, blood samples, ECGs, scans and biopsies taken, they will be
questioned about their medical condition and history, race, ethnicity and they
will be tested for HIV, hepatitis B, C, and cytomegalovirus. Pregnancy must be
avoided by using a highly effective method of birth control from the time of
screening until 12 months after the last dose of epcoritamab.Treatment with
Epcoritamab involves subcutaneous injection (the first injection is followed by
at least 24h hospitalization) and premedication. Risks associated with
participation are side effects, such as B cell depletion, cytokine release
syndrome and neurological symptoms, local reaction to injection site, clinical
tumor lysis syndrome, drug-drug interactions, risks associated with blood
sampling, obtaining a biopt or aspirate, ECG and imaging procedures. CD20
targeting drugs also have known side effects which may occur.

There is an unmet medical need for new efficacious therapies for patients with
B-cell
non-Hodgkin lymphoma (B-NHL).Safety precautions and close monitoring will be
done in this trial to facilitate a positive benefit-risk ratio for each
subject. Subjects with B-cell NHL may benefit from treatment with epcoritamab
combined with SOC therapy in terms of additional disease reduction, as
epcoritamab has a different mode of action from chemotherapy and direct
CD20-targeting monoclonal antibodies. It is expected that there will be minimal
overlapping toxicity with the SOC agents, and that this can be managed with
standard supportive care. The potential benefit of therapy with epcoritamab is
expected to outweigh the treatment-related risks.