The use of single-agent odronextamab demonstrated a manageable safety profile and promising preliminary activity in heavily pretreated patients with B-cell non-Hodgkin lymphoma.
The use of single-agent odronextamab (REGN1979) in a phase 1 study demonstrated a manageable safety profile and promising preliminary activity, including durable responses in heavily pretreated patients with B-cell non-Hodgkin lymphoma (NHL), supporting further clinical investigation 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. Additionally, activity has been observed in a group of 30 highly refractory patients with diffuse large B-cell lymphoma who have progressed following 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 dismal prognosis,” wrote the study authors led by Rajat Bannerji, MD, PhD, chief of Hematologic Malignancies at and professor of Medicine, Division of Blood Disorders at Rutgers Robert Wood Johnson Medical School.
Findings come 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 were previously treated with CD20-directed antibody therapy.2
The single-arm, multicenter, dose-escalation and dose-expansion trial enrolled patients aged 18 and older throughout 10 academic sites across the United States and Germany.
Enrollment in the trial was open to patients with CD20-positive relapsed or refractory B-cell malignancies who previously received CD20-directed antibody therapy, who had at least 1 measurable lesion, and who had an ECOG performance status 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 were administered odronextamab intravenously, according to a step-up dosing schedule in cycle 1. Following this, patients were given treatment once a week at target doses ranging from 0.1 mg to 320 mg during cycles 2-4 which each lasted 21 days. When cycle 4 was complete, maintenance treatment occurred every 2 weeks until patients demonstrated either disease progression or unacceptable toxicity.
The primary end point of the trial was safety as assessed by overall frequency of adverse events and dose-limiting toxicities, and antitumor activity as measured by objective response rate (ORR). Secondary end points of the trial included pharmacokinetics, the incidence of anti-drug antibodies, the incidence of neutralizing antibodies, progression-free survival, overall survival, duration of response, minimal residual disease, and duration of complete response (CR).
A total of 145 heavily pretreated patients were enrolled in the trial with 94 to the dose-escalation portion of the study and 51 to the dose-expansion part. The median age of patients was 67 years (0–73.0) and 70% of patients were male (n = 101) while 30% were female (n = 44). The majority of the participants in the study were White (119 [82%]), and not Hispanic or Latino (132 [91%]). Additionally, 29% of patients received previous chimeric antigen receptor (CAR) T-cell therapy (n = 42) and 82% of patients were refractory to the last line of therapy (n = 119).
The median duration of follow-up was 4.2 months, and during the dose escalation portion of the trial where odronextamab was administered up to the maximum dose of 320 mg once per week, no dose-limiting toxicities were observed. For patients with follicular lymphoma, the recommended dose for expansion was 80mg while it was 160mg for patients with diffuse large B-cell lymphoma.
Findings revealed the ORR was 51% in 71 of 142 patients (95% CI, 42–59). Within patients with follicular lymphoma given odronextamab doses of 5mg or higher, the ORR was shown to be 91% in 29 of the 32 patients (95% CI, 75–98). Further, the complete response rate was 72% shown in 23 of 32 patients (95% CI, 53–86).
Patients with diffuse large B-cell lymphoma without previous CAR T-cell therapy administered doses of 80 mg or higher showed an ORR of 53% (8 of 15) with all responses being complete responses. Additionally, patients with diffuse large B-cell lymphoma who had previous CAR T-cell therapy and received doses of 80 mg or higher had an ORR of 33% (10 of 30) and CR rate of 27% (8 of 30).
In regard to safety, cytokine release syndrome and neurological treatment-emergent adverse events (AEs) were mostly low grade. No AEs led to treatment discontinuation for enrolled patients. 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), with the most frequent consisting of cytokine release syndrome (28%), pyrexia (8%), pneumonia (6%), and infusion-related reaction (4%).
A total of 4 deaths were considered to be related to treatment, including gastric perforation in a patient with gastric involvement by lymphoma, lung infection, pneumonia, and tumor-lysis syndrome.
“Overall, the early safety profile and encouraging antitumour activity support continued research and development of odronextamab,” wrote Bannerji et al.