The bispecific antibody, odronextamab, demonstrated promising antitumor activity and an acceptable safety profile — including with cytokine release syndrome (CRS)–mitigating strategies — among patients with B-cell non-Hodgkin lymphomas (NHLs), according to the results of a phase 1 study presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

“This is an off-the shelf, IV-administered treatment … that binds to CD3 on T cells and CD3 on B cells, including malignant B cells, triggering T cell–mediated cytotoxicity independent of T-cell receptor recognition,” Rajat Bannerji, MD, PhD, of the Rutgers Cancer Institute of New Jersey, and presenter of the study, said.

The phase 1 trial treated 127 patients with relapsed/refractory B-cell NHLs at different dose levels.  All patients received dexamethasone premedication and step-up dosing to mitigate risk for CRS. The coprimary endpoints were safety and dose-limiting toxicities (DLTs), determining the maximum tolerated dose (MTD), and identifying the recommended dosing for the phase 2 portion of the trial. Secondary endpoints included antitumor activity assessments. This analysis includes updated safety and efficacy data.

At baseline, the median patient age was 67 years, and 70.6% were male. Malignancies included large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma, marginal zone lymphoma, and other B-cell NHLs. The majority of patients were refractory to treatment at 80.1%, and the median number of prior lines of treatment was 3 (range, 1-11). There were 66.9% of patients who were double-refractory to alkylating and anti-CD20 agents, and 25.7% had received prior CAR-T therapy.


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Among patients with FL, the objective response rate (ORR) was 90%, with a complete response (CR) rate of 70% in cohorts treated with at least 5 mg weekly of odronextamab. The median duration of CR (DoCR) was not yet reached at the time of presentation, and 81% of CRs were ongoing for up to 41 months.

Among patients with DLBCL treated with at least 80 mg weekly of odronextamab, the ORR, which was comprised only of CRs, was 55% in a cohort of patients who had not received prior CAR-T therapy. The median DoCR has not yet been reached. In the cohort refractory to CAR-T, the ORR was substantially lower, at 33% with a CR rate of 21% and a median DoCR that has not yet been reached.

There were no DLTs and the MTD was not reached with the maximum odronextamab dose of 320 mg weekly. The most common treatment-related adverse events (TRAEs) were pyrexia, CRS, and chills, and 5.9% of patients discontinued treatment due to treatment-related AEs.

CRS of grade 3 severity occurred among 6.6% of patients and grade 4 CRS developed in 1 patient (0.7%), which occurred primarily during the first 2 weeks of step-up dosing. The median time to resolution of CRS was 2 days with supportive care. There was no treatment discontinuation due to CRS. Grade 3 neurotoxicity related to treatment developed in 2.3% of patients; no events of neurotoxicity were grade 4 or higher.

Dr Bannerji concluded that “in this first-in-human phase 1 trial, odronextamab has demonstrated compelling antitumor activating, including durable CRs in heavily pretreated patients with FL and DLBCL.”

Disclosures: Some of the abstract authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.

Editor’s note: On 12/14/20, Regeneron announced it is pausing new enrollment of patients with B-cell non-Hodgkin lymphomas (B-NHL) in its trials for odronextamab in compliance with a US Food and Drug Administration (FDA) partial clinical hold. The FDA requested that the company amend the trial protocols to reduce the incidence of grade 3 or higher cytokine release syndrome during step-up dosing.

Reference

Bannerji R, Allan JN, Arnason JE, et al. Odronextamab (REGN1979), a human CD20 x CD3 bispecific antibody, induces durable, complete responses in patients with highly refractory B-cell non-Hodgkin lymphoma, including patients refractory to CAR T therapy. Presented at: 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-9, 2020. Abstract 400.

This article originally appeared on Cancer Therapy Advisor