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Promising first-in-human trial of epcoritamab in B-NHL

Presented by
Dr Martin Hutchings, Copenhagen University Hospital, Denmark
EHA 2020
Phase 1/2, GEN3013
Dr Martin Hutchings (Copenhagen University Hospital, Denmark) presented the findings of the dose-escalation phase 1-2 GEN3013 trial in B-cell non-Hodgkin lymphoma (B-NHL) in an e-poster [1]. Epcoritamab administered subcutaneously demonstrated a favourable safety profile, with initial data suggesting promising and durable responses.

The rationale behind this study stems from the fact that most B-NHL patients relapse or become refractory (R/R) to CD20-specific monoclonal antibodies, but CD3xCD20 bispecific antibodies have shown promising results and may ameliorate resistance. The current poster presented dose-escalation data from the ongoing trial testing epcoritamab, a novel, subcutaneously administered CD3xCD20 agent. The primary endpoints were to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). A key secondary objective was to analyse initial anti-tumour efficacy.

At the time of data cut-off, 41 R/R CD20+ B-NHL patients (median age of 66), all treated with prior anti-CD20 therapy potentially in combination with chemotherapy and/or relapsed after autologous stem cell rescue, received a single subcutaneous injection of flat-dose epcoritamab in 28-day cycles (every 1 week: cycle 1–2; every 2 weeks: cycle 3–6; every 4 weeks thereafter) until disease progression or unacceptable toxicity. Risk mitigation for cytokine release syndrome included use of corticosteroids and priming and/or intermediate doses of epcoritamab.

With a median follow-up of 4.7 months, no dose-limiting toxicities were observed and MTD was not reached. The most common (>35%) treatment-emergent adverse events (TEAEs) were pyrexia (71%), fatigue (46%), and injection site skin reaction (39%). Cytokine release syndrome was determined by laboratory in 59% patients, but all was grade 1/2 and self-resolved. There were no treatment-related deaths.

Preliminary anti-tumour activity at doses above the 0.76 mg cut-off indicated dose-dependent efficacy and includes complete responses (see Table). These responses appear to be effective and potentially durable as all patients achieving complete response remain in remission.

Table. Anti-tumour activity in R/R B-NHL [1]

Efficacy data are based on snapshots taken on February 11, 2020.
B-NHL, B-cell non-Hodgkin lymphoma; CR, complete response; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; HGBCL, high-grade B-cell lymphoma; ORR, overall response rate; PD, progressive disease; PR, partial response; R/R, relapsed or refractory; SD, stable disease.

In conclusion, subcutaneous epcoritamab had a favourable safety profile across all doses, with no severe or life-threatening events, and no dose-limiting toxicities. Dose-escalation data indicate dose-dependent efficacy, even inducing complete responses in patients with diffuse large B-cell lymphoma/HGBCL. Additional research is warranted; industry and investigators will proceed with phase 2 investigation.

    1. Hutchings M, et al. Subcutaneous epcoritamab (gen3013; cd3xcd20) in patients with relapsed/refractory B-cell non-Hodgkin lymphoma: dose-escalation data from a phase 1/2 trial. EHA25 Virtual, 11-21 June 2020, Abstract EP1218.


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