FDA Lifts Partial Clinical Hold on Odronextamab Studies in Follicular Lymphoma and DLBCL

The FDA has lifted a partial clinical hold that had been placed on the enrollment of patients with follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) to monotherapy trials examining the bispecific antibody odronextamab (formerly REGN19179), according to an announcement from Regeneron Pharmaceuticals, the drug developer.¹

The enrollment to the phase 1 (NCT02290951) and phase 2 (NCT03888105) trials examining the agent in B-cell non-Hodgkin lymphomas will recommence immediately, as trial protocols have been updated to further reduce the incidence of grade 3 or higher cytokine release syndrome (CRS) during step-up dosing.

The hold was placed on the trials in December 2020 after the regulatory agency asked for the pharmaceutical company to amend the protocols to reduce CRS incidence.² During the hold, patients who were enrolled to the trial and were achieving clinical benefit with odronextamab were able to continue treatment following reconsent.

In the open-label, multicenter, dose-escalation phase 1 trial is evaluating the safety and tolerability of odronextamab as an intravenous infusion in patients with B-cell non-Hodgkin lymphomas and chronic lymphocytic leukemia (CLL).³

To be eligible for enrollment, patients needed to have documented CD20-positive B-cell malignancy with active disease that was not responsive to previous treatment. Those with non-Hodgkin lymphoma had to have previous treatment with an anti-CD20 antibody therapy.

To be included in the grades 1 to 3 follicular lymphoma expansion cohort, patients had to have previously received at least 2 lines of systemic treatment, including an anti-CD20 antibody and an alkylating agent. To be included in the disease-specific expansion cohort enrolling patients with DLBCL, patients had to have received CAR T-cell therapy and have recovered from toxicities associated with lymphodepletion therapy and CAR T-cell infusion.

Moreover, patients had to have an ECOG performance status of 0 to 1, a life expectancy of at least 6 months and acceptable bone marrow and organ function.

The primary end point of the research was safety and antitumor activity, while secondary end points included pharmacokinetics, immunogenicity, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and minimal residual disease for patients with CLL.

In the phase 2 trial, investigators are examining the safety and antitumor activity of odronextamab monotherapy in patients with relapsed or refractory B-cell non-Hodgkin lymphomas, including those with grades 1 to 3 follicular lymphoma, those with DLBCL, those with mantle cell lymphoma, those with marginal zone lymphoma, and those with other B-cell non-Hodgkin lymphoma subtypes.⁴

Secondary objectives include antitumor activity of this monotherapy in each of the 5 disease-specific cohorts, ORR per Lugano classification and local investigator assessment, complete response, PFS, OS, duration of response, disease control rate, safety and tolerability, pharmacokinetics, immunogenicity, and patient-reported outcomes.

References

1. Regeneron resumes enrollment of FL and DLBCL patients in odronextamab trials. News release. Regeneron Pharmaceuticals. May 17, 2021. Accessed May 17, 2021. https://bit.ly/3eRho7L
2. Regeneron provides update on odronextamab clinical trials in B-cell non-Hodgkin lymphoma. News release. Regeneron Pharmaceuticals. December 14, 2020. Accessed May 17, 2021. https://bit.ly/2RqA9Gi
3. Study to investigate the safety and tolerability of REGN1979 in patients with CD20+ B-cell malignancies. ClinicalTrials.gov. Updated December 22, 2020. Accessed May 17, 2021. https://clinicaltrials.gov/ct2/show/NCT02290951
4. Assess the anti-tumor activity and safety of odronextamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. ClinicalTrials.gov. Updated December 21, 2020. Accessed May 17, 2021. https://clinicaltrials.gov/ct2/show/NCT03888105