FDA Lifts Partial Clinical Hold on Study of Odronextamab in FL and DLBCL

Regeneron is resuming enrollment of patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) in monotherapy trial of odronextamab (formally REGN19179) after the FDA lifted the partial clinical hold placed on the agent in December 2020, according to a press release by the company.¹

Monotherapy trials of odronextamab, a CD20xCD2 bispecific antibody, for patients with FL and DLBCL (NCT03888105 and NCT02290951) were put on partial clinical hold by the FDA in order to reduce incidences of grade 3 or higher cytokine release syndrome during step-up-dosing.¹ During the hold, patients who were currently enrolled and were deriving clinical benefit from the agent were allowed to continue therapy following re-consent.²

Odronextamab monotherapy for the treatment of FL and DLBCL is currently being evaluated in 2 clinical trials. One is a phase 2 study evaluating the safety and anti-tumor activity of the agent in patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). The second is a phase 1 study evaluating the safety and tolerability of odronextamab in patients with CD20-positive B-cell malignancies.¹

The non-randomized phase 2 study has an estimated enrollment of 481 participants. The primary outcome of the study is objective response rate (ORR). Secondary outcomes include complete response (CR), progression-free survival (PFS), overall survival (OS), duration or response (DOR), duration of complete response , and the incidence and severity of treatment-emergent adverse events. 

The study is made up of 5 arms. During each arm, patients received odronextamab intravenously. Arm 1 was made up of patients with FL. Arm 2 was the DLBCL cohort, arm 3 was the mantle cell lymphoma cohort, arm 4 was the marginal zone lymphoma cohort, and arm 5 was the other B-cell non-Hodgkin lymphoma cohort.

Patients with central nervous system lymphoma (CNS), treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 28 days prior to first administration of the study drug, whichever comes first, and a history of allogeneic stem cell transplant are not eligible to participate.

The phase 1 non-randomized study has an estimated enrollment of 480 participants. The primary outcomes of the study are safety and overall frequency of adverse events (AEs) and antitumor activity as measured by ORR. Secondary measures include pharmacokinetics, immunogenicity, ORR, PFS, OS, and minimal residual disease.

The study is spilt into 2 arms. In arm 1, patients received multiple dose levels of the agent after receiving rituximab (Rituxan). In arm 2, patients received multiple dose levels of odronextamab only.

In order to participate, patients must have document CD20-positive B0cell malignancy with active disease not responsive to prior therapy, at least one bi-dimensionally measurable lesion, and a life expectancy of at least 6 months. Patients with CNS a history of or current relevant CNS pathology, or a history of allogeneic stem cell transplantation are not eligible to participate.

Odronextamab has shown promising antitumor activity and an acceptable safety profile in patients with R/R b-Cell NHL, including in patients who have previously received prior chimeric antigen receptor (CAR) T-cell therapy, according to data presented at the 2020 American Society of Hematology Annual Meeting and Exposition. In patients who have previously received CAR T-cell therapy, the ORR was 33% and the CR rate was 21%. At the time of analysis, 100% of CRs were ongoing. 

In patients who had not received CAR T-cell therapy, the ORR was 55%, 100% of which were CRs. Of those CRs, 83% were durable. For patients with FL, the ORR was 90% and the CR was 70%, and the median CR was not reached. The highest grade of CRS was grade 3, occurring with initial or intermediate step-up doses. The agent was administered at 320mg weekly without reaching the maximum-tolerated dose.

_REFERENCE:

_{1.Regeneron resumes enrollment of FL and DLBCL patients in odronextamab trials. News release. Regeneron. May 17, 2021. Accessed May 17, 2021. https://bit.ly/3whHx5J.}

_{2.Regeneron provides update on odronextamab clinical trials in B-cell non-Hodgkin lymphomas. News release. Regeneron. December 14, 2020. Accessed May 17, 2021. https://bit.ly/33Pd4PY.}