Ordspono (odronextamab)

This review examines CD20 × CD3 bispecific antibodies (BsAbs) like mosunetuzumab, epcoritamab, odronextamab, and glofitamab, which link malignant B-cells and T-cells, thus inducing targeted tumor lysis...This review details their mechanisms, grading, and management, including the use of tocilizumab and corticosteroids...Expert recommendations for antimicrobial prophylaxis, including herpes and varicella zoster virus, pneumocystis, and immunoglobulin supplements are crucial for mitigating these risks. While BsAbs offer an "off-the-shelf" advantage, balancing their efficacy with comprehensive toxicity management is crucial for maximizing patient outcomes.

After weighting, objective response rate (80.5 vs. 52.7%; odds ratio [OR], 3.75 [95% CI, 1.98-7.11]), complete response rate (73.4 vs. 33.6%; OR, 5.39 [95% CI, 2.76-10.53]), median (months) progression-free survival (20.7 vs. 11.5; hazard ratio [HR], 0.76 [95% CI, 0.46-1.24]), event-free survival (19.5 vs. 7.6; HR, 0.52 [95% CI, 0.36-0.77]), overall survival (not reached vs. 26.2; HR, 0.60 [95% CI, 0.37-0.97]), and time to next treatment or death (40.4 vs. 9.7; HR, 0.49 [95% CI, 0.33-0.72]) favored odronextamab versus 3L + RWST. Despite FLORA's limited sample size, these data further support odronextamab monotherapy for 3L + R/R FL.

P3, N=904, Active, not recruiting, Regeneron Pharmaceuticals | Trial completion date: Apr 2029 --> Sep 2029

P1, N=105, Active, not recruiting, Regeneron Pharmaceuticals | Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Dec 2025 --> May 2026

This review focused on 4 CD20 × CD3 BsAbs, as well as surovatamig, a CD19 × CD3 BsAb currently under investigation that has demonstrated promising efficacy against relapsed/refractory B-cell lymphomas. All 4 CD20 × CD3 BsAbs are approved as third-line and beyond therapies: mosunetuzumab for follicular lymphoma (FL), glofitamab for diffuse large B-cell lymphoma (DLBCL), and epcoritamab and odronextamab for both FL and DLBCL (the latter in European Union only)...Multiple studies are currently evaluating these agents in both the relapsed/refractory and frontline settings, either as monotherapy or in combination with other agents. This review summarizes the efficacy and safety of each agent across B-cell lymphoma subtypes, along with their dosing schedules and CRS mitigation strategies.

P1, N=90, Recruiting, Regeneron Pharmaceuticals | Not yet recruiting --> Recruiting

BsAbs targeting CD20/CD3, such as epcoritamab, glofitamab, mosunetuzumab, and odronextamab, are rapidly progressing toward widespread clinical application. Although monotherapy remains the standard approach, clinical trials are exploring earlier-line use and combination strategies to further enhance outcomes. Particular attention is given to predictive biomarkers of response and mechanisms of resistance, including target antigen loss, tumor histology, prior therapies, intratumoral and peripheral T-cell status, and the emerging role of minimal residual disease monitoring.

Target-mediated clearance was ~5 L/day at baseline, with an asymptote of ~0.03 L/day at steady state. With the largest covariate effect on odronextamab exposure, baseline body weight was directly correlated with CL and volume of distribution, albumin was inversely correlated with CL and volume of distribution, and baseline interleukin-10 was inversely correlated with CL.

P2, N=515, Active, not recruiting, Regeneron Pharmaceuticals | Trial completion date: Dec 2029 --> Dec 2028 | Trial primary completion date: Aug 2028 --> Jul 2026 | Recruiting --> Active, not recruiting

Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R/R) disease. Recently, the introduction of Pola-R-CHP as front-line therapy has represented a major advance in the management of DLBCL, resulting in improved outcomes...The most extensively studied BsAbs, in both the frontline and relapsed/refractory (R/R) settings, include epcoritamab, glofitamab, mosunetuzumab, and odronextamab...EMA has also approved glofitamab in combination with gemcitabine and oxaliplatin (GemOx) for patients with R/R DLBCL ineligible for ASCT, whereas this indication has not been approved by FDA...BsAbs represent a breakthrough therapy in the treatment of DLBCL, especially in R/R diseases. The purpose of this article is to review the landscape of BsAbs in DLBCL.

P1, N=126, Not yet recruiting, Regeneron Pharmaceuticals | N=72 --> 126

This study provides mechanistic insights into how cardiorenal medications improve systemic function via sugar, water, and salt modulation. Additionally, it presents a validated, optimized dosing strategy for odronextamab that reduces IL-6 levels and enhances safety in B-NHL patients. Integrating QSP with real-world data supports personalized pharmacotherapy and underscores the utility of computational modeling in drug development and clinical decision-making.