MBS303, a Novel 2:1 CD20×CD3 Bispecific Antibody, Demonstrated a Favorable Safety and Potent Antitumor Activity in Patients with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphoma: Preliminary Results from a Phase Ⅰ, Dose-Escalation Trial
Authors: Song Yuqin , Yang Haiyan , Jia Youchao , Sheng Lixia , Deng Lijuan , Chen Xi , Tang Yongjing , Liu Xifang , Liu Sijun , Wei Min , Li Feng 
Published: December 2024

Background:

New treatment options are needed for patients (pts) with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL), especially those with aggressive B-NHL. MBS303 is a CD20×CD3 T-cell-engaging bispecific antibody that has a novel 2:1 (CD20:CD3) configuration to kill malignant B cells. This dose-escalation phase Ⅰ trial evaluated the safety and efficacy of single-agent MBS303 in pts with R/R NHL (NCT05806099).

Methods:

Pts with refractory or relapse (R/R) NHL with ≥1 prior line of therapy that must including anti-CD20 antibody (diffuse large B-cell lymphoma not otherwise specified [DLBCL NOS], high-grade B-cell lymphoma [HGBCL], primary mediastinal large B-cell lymphoma [PMBCL], transformed follicular lymphoma [trFL] or follicular lymphoma [FL]) were enrolled. The dose-escalation part (7 cohorts ranging from 0.45 to 30 mg) of this phase I, multicenter, single-arm, open-label clinical trial has enrolled at 4 study sites in China. The study objectives include safety, dose finding (Recommended Phase II Dose), and antitumor activity. Eligible pts received intravenous (IV) step-up dosing (SUD) of MBS303 in a 28-day dose limiting toxicity (DLT) period, and then a target dose from C2D1 every 3 weeks for up to 17 cycles or until disease progression or unacceptable toxicity. Response was investigator-assessed using Lugano criteria (Cheson et al. JCO 2014).

Results:

As of Jul 20th, 2024, 4 cohorts were enrolled. Ten pts who received ≥1 dose of study treatment were evaluable. Median age was 56 years (range: 51-70), 70% were female and 80% of pts had Ann Arbor stage III/IV. The median number of prior therapies received was 2.5 (range: 1-4; ≥3 prior therapies: 50%). Most pts (80%) were refractory to prior therapy and 7 pts (70%) were refractory to any line of prior CD20 therapy. The median number of MBS303 cycles administered was 3.5 (range: 1-16).

Maximum tolerated dose was not reached. Three pts (30%) experienced cytokine release syndrome (CRS), and all were grade [G]1-2, no G 3 or higher. Most CRS occurred in 1st cycle, and resolved within 48 hours. No pts experienced neurologic events. Three pts (30%) experienced serious adverse events (SAE) related to MBS303, 2 pts with infection and 1 pt with aminotransferase increased.

In R/R B-NHL pts received MBS303 ≥9 mg (n=7), the objective response rate (ORR) was 71%, and complete metabolic response (CMR) was 43% (all in 9 mg). In FL pts of 9 mg (n=2), ORR and CMR were both 100%. Even at first cohort with target dose of 0.45 mg, response was also observed and this pt with r/r DLBCL achieved partial response.

Conclusion:

This study demonstrated that in pts with refractory, aggressive B-NHL, MBS303 showed favorable safety and remarkable antitumor activity in the preliminary data, even at low doses.