The use of odronextamab as monotherapy (REGN1979) in a phase 1 study demonstrated a manageable safety profile and promising preliminary activity, including durable responses in heavily pretreated patients with non-Hodgkin’s lymphoma ( NHL) to B cells, supporting further clinical study in phase 2 and 3 trials.1
“Data from dose escalation studies are often confounded by the inclusion of results from patients treated at suboptimal doses. This study provides preliminary validation of early activity signals previously observed with shorter follow-up. Moreover, activity was observed in a group of 30 highly refractory patients with diffuse large B-cell lymphoma who progressed after CAR T-cell therapy.To our knowledge, this study is the first to report durable remissions at 12 months in these patients, who would otherwise have a poor prognosis,” wrote the authors of the study led by Rajat Bannerji, MD, PhD, chief of hematologic malignancies at Rutgers and professor of Medicine, Division of Blood Disorders. Robert Wood Johnson Medical School.
Results are from the ELM-1 trial (NCT02290951) evaluating the safety and tolerability of the anti-CD20 x anti-CD3 bispecific monoclonal antibody, odronextamab, in patients with CD20-positive B-cell malignancies who have been previously treated with an antibody directed against CD20 therapy.2
The single-arm, multicenter, dose-escalation, dose-expansion trial enrolled patients ages 18 and older at 10 university sites in the United States and Germany.
Enrollment in the trial was open to patients with relapsed or refractory CD20-positive B-cell malignancies who had previously received anti-CD20 antibody therapy, had at least 1 measurable lesion, and had a performance status ECOG of 0 or 1. Other requirements included a life expectancy of at least 6 months, adequate bone marrow function, and adequate organ function.
Patients in the trial received odronextamab intravenously in a tapered dosing regimen during cycle 1. Following this, patients received once-weekly treatment at target doses ranging from 0.1 mg to 320 mg for cycles 2 to 4 which each lasted 21 days. After cycle 4 was completed, maintenance therapy occurred every 2 weeks until patients experienced disease progression or unacceptable toxicity.
The primary endpoint of the trial was safety assessed by the overall frequency of adverse events and dose-limiting toxicities, and antitumor activity as measured by objective response rate (ORR). Secondary endpoints of the trial included pharmacokinetics, incidence of anti-drug antibodies, incidence of neutralizing antibodies, progression-free survival, overall survival, duration of response, minimal residual disease and the duration of the complete response (CR).
A total of 145 heavily pretreated patients were enrolled in the trial, including 94 in the dose escalation part of the study and 51 in the dose expansion part. The median patient age was 67 years (0–73.0) and 70% of patients were male (n=101) while 30% were female (n=44). The majority of study participants were white (119 [82%]), not Hispanic or Latino (132 [91%]). In addition, 29% of patients had previously received chimeric antigen receptor (CAR) T-cell therapy (n=42) and 82% of patients were refractory to last-line therapy (n=119).
The median duration of follow-up was 4.2 months, and during the dose-escalation part of the trial where odronextamab was administered up to the maximum dose of 320 mg once weekly, no dose-limiting toxicities was not observed. For patients with follicular lymphoma, the recommended dose for expansion was 80 mg while it was 160 mg for patients with diffuse large B-cell lymphoma.
The results revealed that ORR was 51% in 71 of 142 patients (95% CI, 42-59). In follicular lymphoma patients who received odronextamab doses of 5 mg or more, ORR was found to be 91% in 29 of 32 patients (95% CI, 75-98). Additionally, the complete response rate was 72% in 23 of 32 patients (95% CI, 53–86).
Patients with diffuse large B-cell lymphoma without prior treatment with CAR T-cell administered doses of 80 mg or more showed an ORR of 53% (8 of 15), with all responses being complete responses. Additionally, patients with diffuse large B-cell lymphoma who had previously received CAR T-cell therapy and who received doses of 80 mg or more had an ORR of 33% (10 of 30) and a CR rate 27% (8 out of 30).
Regarding safety, cytokine release syndrome and treatment-related neurological adverse events (AEs) were mostly low grade. No AE led to discontinuation of treatment for the patients included. Grade 3 or worse treatment-emergent AEs observed in patients were anemia (25%), lymphopenia (19%), hypophosphatemia (19%), neutropenia (19%) and thrombocytopenia (14%). ). Serious treatment-emergent AEs occurred in 61% of patients (n=89), the most common being cytokine release syndrome (28%), pyrexia (8%), pneumonia (6%), and infusion-related reaction (4%).
A total of 4 deaths were considered treatment-related, including gastric perforation in a patient with gastric involvement with lymphoma, lung infection, pneumonia, and tumor lysis syndrome.
“Overall, the early safety profile and encouraging antitumor activity support further research and development of odronextamab,” wrote Bannerji et al.
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’s lymphoma cohort in a single-arm, multicenter phase 1 trial. Hematol Lancet. 2022;9(5):e327-e339. doi:10.1016/S2352-3026(22)00072-2
Study to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies (ELM-1). Clinicaltrials.gov. Updated April 29, 2022. Accessed May 11, 2022. https://clinicaltrials.gov/ct2/show/NCT02290951