As reported in the Journal of Clinical Oncology by Catherine Thieblemont, MD, PhD, and colleagues, findings in a dose-expansion cohort of the phase I/II EPCORE NHL-1 study indicated high activity of the subcutaneous CD3 x CD20 T-cell–engaging bispecific antibody epcoritamab in patients with relapsed or refractory CD20-positive large B-cell lymphoma.

Catherine Thieblemont, MD, PhD

Study Details

The international study included 157 patients who received epcoritamab between June 2020 and data cutoff at the end of January 2022. Patients had received at least two prior lines of therapy, including anti-CD20 therapy. Treatment consisted of 28-day cycles, beginning with once-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 48 mg on day 15), followed by 48 mg once weekly through cycle 3, once every 2 weeks in cycles 4 to 9, and once every 4 weeks in cycle 10 and thereafter. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall response rate on independent review committee assessment.

Responses

Median follow-up was 10.7 months. Objective response was observed in 99 (63.1%, 95% confidence interval [CI] = 55.0%–70.6%) of 157 patients, with complete response seen in 61 (38.9%, 95% CI = 31.2%–46.9%). Median time to response was 1.4 months (95% CI = 1.0–8.4 months). Median duration of response was 12.0 months (95% CI = 6.6 months to not reached; range = 0.0+ to 15.5+ months). Median duration of response among those with complete response was not reached (95% CI = 12.0 months to not reached; range = 1.4+ to 15.5+ months). 

Among key prespecified subgroups, objective and complete response rates were 55.2% and 30.2% among 96 patients with primary refractory disease, 54.1% and 34.4% among 61 patients who had received prior chimeric antigen receptor (CAR) T-cell therapy (median response duration = 9.7 months, not reached in complete responders), and 68.8% and 41.7% among 96 patients who had not received prior CAR T-cell therapy (median response duration = 12 months, not reached in complete responders).

Median progression-free survival was 4.4 months (95% CI = 3.0–7.9 months; range = 0.0+ to 16.9+ months), with the median not reached (95% CI = 14.5 months to not reached) among complete responders. Median overall survival was not reached (95% CI = 11.3 months to not reached; range = 0.3 to 17.9+ months).

Adverse Events

The most common adverse events of any grade were cytokine-release syndrome (49.7%; grade 3 in 2.5%, no grade ≥ 4 events), pyrexia (23.6%), fatigue (22.9%), neutropenia (21.7%), and diarrhea (20.4%). Grade ≥ 3 adverse events occurred in 66.1% of patients, most commonly neutropenia (14.6%), anemia (10.2%), and thrombocytopenia (5.7%). Immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 6.4% of patients, with one fatality. Adverse events led to treatment discontinuation in 7.6% of patients. Adverse events led to death in nine patients (5.7%), with causes consisting of COVID-19 infection in two patients, and myocardial infarction, hepatotoxicity, progressive multifocal leukoencephalopathy, loss of consciousness, general health deterioration, pulmonary embolism, and ICANS in one patient each; only the death due to ICANS was considered related to treatment.

The investigators concluded, “Subcutaneous epcoritamab resulted in deep and durable responses and manageable safety in highly refractory patients with large B-cell lymphoma, including those with prior CAR T-cell [therapy] exposure.”

Dr. Thieblemont, of Assistance Publique & Hôpitaux de Paris, Hôpital Saint-Louis, Université de Paris, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Genmab A/S and AbbVie. For full disclosures of the study authors, visit ascopubs.org.