Abstract CT060: First-in-human trial of JMT601, a bispecific fusion protein targeting CD47 and CD20, in patients with relapse/refractory CD20 positive B-cell non-Hodgkin lymphoma

Abstract Background: JMT601 is a bi-specific left-right asymmetrical fusion protein comprised of a high CD20 binding affinity Fab arm and a low CD47 binding fragment SIRPα, without binding CD20-negative lymphoma cells, RBCs and platelet. JMT601 was more effective in multiple human B-cell lymphoma models than conventional CD20-targeted antibodies monotherapy and in combination with SIRPα, but without severe anemia and thrombocytopenia. Here we present the preliminary safety and efficacy of JMT601 in patients with relapse/refractory CD20 positive B-cell NHL. Methods: Patients aged 18-70 years with histologically confirmed B-cell NHL (including diffused large B-cell lymphoma, DLBCL; follicular lymphoma, FL; mantle cell lymphoma, MCL), relapsed or refractory disease after ≥2 prior lines of therapy, ECOG performance score 0-2 and at least one measurable/evaluable lesion as per Lugano 2014 were recruited. This study consisted of dose-escalation part (1) and dose-expansion part (2). Part 1 was 3+3 dose-escalation design with eight dose levels of JMT601 (0.3, 1, 3, 6, 12, 20, and 30 mg/kg) intravenously administered weekly until disease progression, intolerable toxicity, or consent withdrawal. Part 2 was dose expansion at the recommended dose in selected tumor types. The primary endpoints were safety and tolerability. Results: At the cut-off date of August 20, 2024, 36 eligible patients (23 males; Lugano Classification III-IV disease: 58.3%) were enrolled (30 in part 1, 6 in part 2), including 31 DLBCL, 4 FL and 1 MZL. Median age was 59.0 (range, 24-75). 27 patients (75.0%) had ≥3 prior lines of therapy. 27 patients (75.0%) were refractory to prior rituximab-based combination therapy. One dose-limiting toxicity (grade 4 thrombocytopenia) occurred at 12 mg/kg dose level, MTD was not reached. Treatment-related adverse events (TRAEs) of any grade occurred in 31 (86.1%) patients, in which 16 (44.4%) were ≥ grade 3. The most common ≥ grade 3 TRAEs were neutropenia (19.4%), thrombocytopenia (13.9%), leukopenia (11.1%), lymphocytopenia (8.3%), hypertriglyceridemia (5.6%), amenia (5.6%) and infectious pneumonia (5.6%). 9 (25.0%) patients experienced serious adverse events (SAEs), of which 3 had treatment related SAEs (2 thrombocytopenia and 1 infectious pneumonia). One patient died due to disease progression, which was not related to JMT601 treatment judged by the investigator. 32 patients were efficacy evaluable, objective response rate (ORR) was 25.0% (8/32, 95% CI 11.5-43.4), disease control rate (DCR) was 50%. ORR and DCR were 28.0% (7/25) and 52.0% (13/25) for DLBCL, 25.0% (1/4) and 50.0% (2/4) for FL/MZL, respectively. Conclusion: JMT601 had an encouraging anti-tumor effect in relapse/refractory CD20 positive B-cell NHL patients with acceptable safety profiles. This trial is registered at ClinicalTrials.gov (NCT06725524). Citation Format: Weili Zhao, Shu Cheng, Wenjuan Yu, Juying Wei, Yunhong Huang, Yunfei Hu, Qiangxing Zeng, Lier Lin, Zhenyu Zhao, Mengling Duan, Yueqing Chen, Zhigang Peng, Haiyan Yang, Ming Jiang, Fei Li, Yulan Zhou, Li Wang, Pengpeng Xu, Huijuan Zhong, Guodong Luan, Wenfeng Mao, Yanyan Xiao, Yitao Wang, Lifang Shu. First-in-human trial of JMT601, a bispecific fusion protein targeting CD47 and CD20, in patients with relapse/refractory CD20 positive B-cell non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT060.