836P - EX103, a re-designed CD20xCD3 bispecific antibody, showed a favorable safety and potent single-agent antitumor activity in heavily pretreated relapsed/refractory patients with B cell non-Hodgkin lymphoma

Background

In recent years, T cell engaging bispecific antibody emerged as a promising therapy in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). However, severe cytokine release syndrome (CRS) remains to be a significant challenge in TCB treatment. To overcome this issue, we re-designed a new CD20xCD3 bispecific antibody (EX103) with a much lower affinity to CD3. The new molecule induced significantly lower IL-6 release in preclinical tox study. Preliminary EX103 phase I dose escalation data demonstrates a favorable safety and a promising single-agent antitumor activity, in heavily pretreated R/R B-NHL patients.

Methods

The dose-escalation part (8 cohorts ranging from 1.2 to 36 mg) of this phase I, multicenter, single-arm, open-label clinical trial has enrolled at 4 study sites in China. Objectives include safety, dose finding (RP2D), and antitumor activity. Eligible patients received intravenous(iv) step-up doses of EX103 (with 1 priming dose and 2 intermediate doses followed by 1 target dose) in a 28-day dose limiting toxicity (DLT) period, and then a target dose every 2 weeks for up to 24 cycles or until disease progression or unacceptable toxicity. As of July 2023, 5 cohorts were completed.13 patients were evaluable. The median number of prior lines of treatment was 5 (2–8).

Results

Maximum tolerated dose was not reached. The most common adverse events were CRS and pyrexia, all were grade (Gr) 1-2, no Gr 3 or higher. Most CRS occurred in 1st or 2nd cycle, and resolved within 48 hours. No neurologic AE occurred. In DLBCL patients received EX103 ≥6mg (n=4), the overall response rate (ORR) was 75.0%, including 3 Complete Response (CR) (1 each in 6 or 12 or 18 mg) . In FL/MZL patients ≥6mg (n=4), ORR was 100.0%, 3 FL (1 each in 6 or 12 or 18 mg) and 1 MZL (12 mg) achieving Partial response (PR). 1 MCL patient (3mg) achieved CR. 1 CLL patient (3mg) achieved SD.For 2 patients who failed prior CAR-T therapy, one achieved PR (12mg) and another achieved SD (18mg). The preliminary Disease Control Rate (DCR) is 84.6% (11/13).

Conclusions

The preliminary data show favorable safety and remarkable antitumor activity, even at low doses, in heavily pretreated patients with R/R B-NHL, including those who failed prior CAR-T therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Guangzhou Excelmab Inc.

Funding

Guangzhou Excelmab Inc.

Disclosure

W. Zhang: Financial Interests, Personal and Institutional, Leadership Role: Guangzhou Excelmab Inc. D. Yang: Financial Interests, Personal and Institutional, Full or part-time Employment: Guangzhou Excelmab Inc. J. Lu, J. Li, Y. Cheng, Y. Li: Non-Financial Interests, Personal and Institutional, Full or part-time Employment: Guangzhou Excelmab Inc. All other authors have declared no conflicts of interest.