Odronextamab Demonstrates Promising Safety, Response in R/R Non-Hodgkin Lymphoma

Odronextamab monotherapy demonstrated a manageable safety profile and encouraging preliminary activity, including durable responses, in heavily pretreated patients with B-cell non-Hodgkin lymphoma, according to a phase 1 study published in The Lancet Haematology.

“Odronextamab is a hinge-stabilised, fully human IgG4-based CD20-CD3 bispecific antibody that binds CD3 on T cells and CD20 on B cells,” wrote Rajat Bannerji, MD, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, and colleagues.

The single-arm, multicenter, phase 1, dose-escalation and dose-expansion (ELM-1) trial was conducted across 10 academic sites in the USA and Germany from February 4, 2015, to September 25, 2021. The study enrolled 145 patients with CD20-positive relapsed or refractory B-cell malignancies, who previously received CD20-directed antibody therapy and who had at least 1 measurable lesion. There were 94 patients in the dose-escalation stage and 51 in the dose-expansion stage. Of all the patients, 42 (29%) patients received previous CAR T-cell therapy and 119 (82%) were refractory to the last line of therapy.

Patients received intravenous odronextamab in 28-day cycles. In cycle 1,  dosing followed a step-up schedule. In cycles 2 to 4, treatment was once per week at target doses ranging from 0.1 mg to 320 mg. After cycle 4, maintenance treatment was administered every 2 weeks until disease progression or unacceptable toxicity. The primary end point was safety, determined by incidence of adverse events and dose-limiting toxicities to determine the maximum tolerated dose or phase 2 dose, or both. The secondary end point was objective response rate.

The median duration of follow-up was 4.2 months. During dose escalation, odronextamab was administered up to the maximum dose of 320 mg once per week, and no dose-limiting toxicities were observed. The recommended dose for expansion in patients with follicular lymphoma grade 1 to 3a was 80 mg and for patients with diffuse large B-cell lymphoma the dose was 160 mg.

The most common grade 3 or worse treatment-emergent adverse events were anemia (25%), lymphopenia (19%), hypophosphatemia (19%), neutropenia (19%), and thrombocytopenia (14%). Cytokine release syndrome and neurological treatment-emergent adverse events were predominantly low grade and did not result in treatment discontinuation. Serious treatment-emergent adverse events occurred in 89 (61%) of 145 patients; the most frequent were cytokine release syndrome (28%), pyrexia (8%), pneumonia (6%), and infusion-related reaction (4%). There were 4 treament-related deaths (1 each attributed to gastric perforation in a patient with gastric involvement by lymphoma, lung infection, pneumonia, and tumor-lysis syndrome).

The objective response rate was 51% (72 of 142; 95% confidence interval [CI], 42 to 59;). In patients with follicular lymphoma who received odronextamab doses of ≥5 mg, the objective response rate was 91% (29 of 32; 95% CI, 75 to 98) and the complete response rate was 72% (23 of 32; 95% CI, 53 to 86). In patients with diffuse large B-cell lymphoma who had not had previous CAR T-cell therapy who received doses of ≥80 mg, the objective response rate was 53% (8 of 15) and all responses were complete responses. In patients with diffuse large B-cell lymphoma who had previous CAR T-cell therapy and received doses of ≥80 mg, the objective response rate was 33% (10 of 30) and complete response rate was 27% (8 of 30).

“Odronextamab monotherapy showed a manageable safety profile and encouraging preliminary activity, including durable responses in heavily pretreated patients with B-cell non-Hodgkin lymphoma, supporting further clinical investigation in phase 2 and 3 trials,” Dr Bannerji and colleagues concluded.

Source:

Bannerji R, Arnason JE, Advani RH, et al. Odronextamab, a human CD20×CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): Results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. The Lancet Haematol. 2022;9(5):e327-e339. doi:10.1016/s2352-3026(22)00072-2