Clinical trialLymphoma

Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial

J Clin Oncol · 2023157 patients

Thieblemont C, Phillips T, Ghesquieres H, et al. J Clin Oncol. 2023. 41:2238-2247

A newer report of this study has been published: Efficacy and safety of epcoritamab in relapsed or refractory large B-cell lymphoma: 3-year update from the EPCORE NHL-1 trial. (2026)

Study type: Clinical trial
Study name: EPCORE NHL-1
Design: Single-arm, open-label, multicentre study
Sample size: 157 patients
Source: J Clin Oncol · 2023
Trial registration: NCT03625037

In plain words

Epcoritamab is a two-armed (bispecific) antibody that links immune cells to lymphoma cells, but it is given as an injection under the skin. In patients whose several previous treatments (even CAR-T) had failed, about 6 out of 10 responded and nearly 4 out of 10 went into complete remission. Fever and low blood pressure (CRS) are usually mild and happen in the first weeks; less often, confusion or nerve problems can occur and must be reported straight away.

Key results

63.1%

Overall response rate

95% CI 55.0 to 70.6; median follow-up 10.7 months

38.9%

Complete response

95% CI 31.2 to 46.9

12.0 months

Median duration of response

In complete responders: not reached

Dose and schedule cards

Single-agent epcoritamab

DLBCL or high-grade B-cell lymphoma, relapsed or refractory after at least 2 lines of systemic therapyCycle length: Every 28 daysOn the page “Lymphoma” · Treatment regimens and dosing: relapsed or refractory DLBCL, transplant-ineligible and later lines

DLBCL or high-grade B-cell lymphoma, relapsed or refractory after at least 2 lines of systemic therapy

Drug	Dose	Route	Schedule
Cycle 1
Epcoritamab	0.16 mg (Day 1), 0.8 mg (Day 8), 48 mg (Days 15 and 22)	SC	Days 1, 8, 15 and 22
Cycles 2 and 3
Epcoritamab	48 mg	SC	Days 1, 8, 15 and 22
Cycles 4–9
Epcoritamab	48 mg	SC	Days 1 and 15
Cycle 10 onward
Epcoritamab	48 mg	SC	Day 1

Cycle length: Every 28 days
Duration: Until disease progression or unacceptable toxicity

Per the FDA label for EPKINLY: in cycle 1, dexamethasone 15 mg (or prednisolone 100 mg) 30 to 120 minutes before each dose and for three days afterward, plus diphenhydramine and acetaminophen; Pneumocystis prophylaxis is mandatory and herpes prophylaxis is recommended; after the first 48 mg dose (cycle 1, Day 15), assess the need for hospitalisation or outpatient monitoring. CRS occurred in 51% of patients, mostly grade 1–2.

On the page “Lymphoma” · Treatment regimens and dosing: relapsed or refractory DLBCL, transplant-ineligible and later lines

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Subcutaneous epcoritamab

Epcoritamab subcutaneously in 28-day cycles: weekly step-up doses in weeks 1 to 3 of cycle 1 (0.16 mg on day 1, 0.8 mg on day 8 and the first full dose of 48 mg on day 15), then 48 mg weekly to the end of cycle 3, every 2 weeks in cycles 4 to 9 and every 4 weeks from cycle 10 onwards, until disease progression or unacceptable toxicity.

Source of the regimen details: Abstract of the paper (schedule) and the FDA label for EPKINLY (doses 0.16/0.8/48 mg for DLBCL, 2026 version)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Adults with relapsed or refractory CD20-positive large B-cell lymphoma after at least two prior lines of therapy (including anti-CD20 therapy). Median age 64 years; median of 3 prior lines of therapy; 61.1% primary refractory disease and 38.9% prior CAR-T therapy.

Endpoints

Primary endpoint: overall response rate by independent review committee.

Secondary endpoints: complete response, duration of response, survival and safety.

Safety and side effects

Cytokine release syndrome (CRS) in 49.7% (grade 1 or 2: 47.1%; grade 3: 2.5%). Immune effector cell-associated neurotoxicity syndrome (ICANS) in 6.4%, with one fatal case. Other common adverse events: pyrexia 23.6% and fatigue 22.9%.

Clinical significance and place in guidelines

Based on this study, in May 2023 the FDA granted accelerated approval to epcoritamab (Epkinly) for relapsed or refractory DLBCL after two or more lines of systemic therapy, and the EMA granted conditional approval. Epcoritamab and glofitamab are now standard options after second line, particularly for patients unsuitable for CAR-T or after CAR-T failure. Their use in earlier lines is being studied in phase 3 trials.

Limitations

The study is single-arm without a comparator group, and follow-up in this report was short (median 10.7 months). The primary endpoint is response rate, not survival. Unlike glofitamab, treatment continues until disease progression.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.