EX103: A newly designed CD20×CD3 molecule in heavily pre-treated patients with B-cell non-Hodgkin lymphoma from a phase I/II trial

• Published in: Journal of clinical oncology Vol. 42; no. 16_suppl; p. 7022
• Main Authors: Sun, Mingyuan, Qi, Junyuan, Zhou, Keshu, Liu, Xingchen, Hu, Kai, Chang, Chunkang, Wu, Dong, Li, Zhenling, Gong, Ming, ZHANG, WENJUN, Yang, Daniel Chunxu, LU, JIALI
• Format: Journal Article
• Language: English
• Published: 01.06.2024
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2024.42.16_suppl.7022

7022 Background: T-cell-engaging bispecific antibody (TCB) had emerged as a promising therapy for blood malignancies, including relapsed/refractory (R/R) B-NHL. However, severe cytokine release syndrome (CRS) remains to be a significant challenge in TCB treatment. To overcome this setback, we re-designed a new CD20xCD3 bispecific antibody (EX103) with a lower affinity to CD3. Clinical data from an ongoing first-in-human phase I/II study demonstrates that EX103 has an encouraging safety and promising single-agent antitumor activity in heavily pretreated R/R B-NHL patients. We present updated safety and efficacy data from the ongoing trial (CTR20212096). Methods: Eligible patients received EX103 with 3 step-up doses followed by target doses in 28-day cycles (iv, QW: cycle 1-2; Q2W thereafter) until disease progression or unacceptable toxicity. At data cut off (Dec 24, 2023), a total of 23 patients were evaluated, including 18 patients in dose-escalation part and 5 patients in dose-expansion part. Results: Among 23 evaluable patients (median age: 51 years [range 42-70]; median prior lines of treatment: 4 [range 2-10]), 13 patients had diffuse large B-cell lymphoma (DLBCL), 4 had FL 1-3a, 2 had FL grade 3B, 1 had marginal zone lymphoma, 1 had mantle cell lymphoma, and 2 had chronic lymphocytic leukemia. Median time since last therapy was 2.5 (range 0.3-39.2) months. No DLT and treatment-related death were observed. CRS was the most common treatment related adverse event. All CRS events were grade (Gr) 1-2 (Gr 1: 78.3%, Gr 2: 13.0%), no Gr 3 or higher events. Most CRS events occurred in the first or second treatment cycle, and all CRS-related clinical symptoms were resolved within 48 hours. No cases of immune effector cell-associated neurotoxicity syndrome or other clinically significant neurologic AEs were observed. For dose ≥ 6 mg cohorts, the overall response rate (ORR) for aggressive B-NHL is 78.6% and the complete response (CR) rate is 50.0% (14 patients). Meanwhile, the ORR for indolent B-NHL is 100%, and CR rate is 25.0% (4 patients). The overall DCR is 89.5%. Currently, treatment is ongoing for 18 patients. The longest duration of response is 14 months. Patients who were refractory to previous therapies achieved impressive responses to EX103 treatment. 3 patients who failed CAR-T therapy achieved either CR or partial response (PR) (2 CR and 1 PR), 2 patients who failed CD19×CD3 bispecific antibody treatment both achieved PR, and 4 patients who failed ASCT achieved either CR or PR (2 CR and 2 PR). Conclusions: EX103 can induce deep and durable responses in heavily pretreated patients with R/R B-NHL, such as those patients who failed CAR-T treatment (3 cases), CD19xCD3 bispecific antibody treatment (2 cases) and ASCT (4 cases). Clinical trial information: CTR20212096.