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1719 GB261, an Fc-Function Enabled and CD3 Affinity De-Tuned CD20/CD3 Bispecific Antibody, Demonstrated a Highly Advantageous Safety/Efficacy Balance in an Ongoing First-in-Human Dose-Escalation Study in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma

Program: Oral and Poster Abstracts
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster I
Hematology Disease Topics & Pathways:
drug development, Therapies
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Yuqin Song, MD1, Zengjun Li2*, Ling Li3*, Zhengzi Qian4*, Keshu Zhou, MD5*, Lei Fan6*, Peter Tan7*, Pratyush Giri, MBBS8*, Zhiming Li9*, Melita Kenealy10*, Jie Jin11, Wei Liu, MD12*, Shafqat Inam13*, Yan Xie14*, Xia Guo15*, Wenduo He15*, Raymond Xu15*, Tong Li15* and Jun Zhu14*

1Department of Lymphoma, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, BEIJING, China
2Department of Lymphoma and Hematology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Ji'nan, Shandong, China
3Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
5Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
6Jiangsu Province Hospital, Nanjing, Jiangsu, China
7One Clinical Research, Nedlands, Australia
8Royal Adelaide Hospital, Adelaide, Australia
9Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
10Cabrini Hospital, Melbourne, AUS
11The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
12State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College, Tianjin, China
13Department of Malignant Haematology & Stem Cell Transplantation, The Alfred Hospital, Melbourne, VIC, Australia
14Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Minis-try of Education), Peking University Cancer Hospital & Institute, Beijing, China
15Genor Biopharma Co., Ltd., Shanghai, China


GB261 is a novel and highly differentiated CD20/CD3 bispecific T cell engager antibody computationally designed to maintain Fc effector function, i.e., antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC) to broaden the mechanisms of action (MOA) for tumor cell killing. Furthermore, the “imbalanced” design of GB261 integrates de-tuned CD3 binding to reduce CRS incidence and improve safety features of the Fc effector function. Extensive pre-clinical studies have shown that GB261 has a highly advantageous safety/efficacy balance. Here, we present the preliminary clinical safety and efficacy results of an ongoing phase I/II study for GB261 (NCT04923048).


This is an open-label, multicenter (China and Australia), dose-escalation/expansion phase 1/2 study of GB261 to evaluate the safety, tolerability and efficacy in patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma(B-NHL) and Chronic Lymphocytic Leukemia (CLL). Adult patients were eligible when they have CD20+ r/r B-NHL or CLL with no available standard of care treatments, adequate organ function, and no CNS involvement or other CNS disease, infections or other active/serious medical issues that may affect compliance or interpretation of results. GB261 was administered in 21-day cycles, weekly (QW) for the first 6 doses followed by every 3 weeks (Q3W) until disease progression, or other situation defined in protocol. Response assessment was based on Lugano 2014 and LYRIC 2016 criteria.


As of June 17, 2023, 47 r/r B-NHL patients (DLBCL:76.6%; FL:23.4%) were enrolled at flat or step-up doses of GB261 ranging from 1mg to 300 mg. Median age was 60.0 years (range: 28, 81), 55.3% of patients were male. Median prior lines of therapy were 3 (range: 1, 10). 78.7% of patients were refractory to any anti-CD20 therapy, 70.2% refractory to their last systemic therapy. Median time since last prior therapy to first study treatment was 1.9 months.

In efficacy evaluable patients (n=22) from 3mg to 100mg, with at least 75% dose exposure before the first radiographic assessment, the median duration of study follow-up was 4.5 months (95%CI: 4.0, 7.4). The overall response rate (ORR) was 73% (16/22), and complete response rate (CRR) was 45.5% (10/22). ORR and CRR were 100% and 100% in 3mg, 56% and 22% in 10mg, 67% and 33% in 30mg. At 100mg dose, there were 5 evaluable patients, with ORR 100% (5/5), CRR 80% (4/5) and PR (20%, 1/5; mosunetuzumab-refractory rrDLBCL patient). Median time to response (TTR) was 1.3 months (95%CI: 1.2, 1.5), the same as median time to CR. Median duration of response (DOR) was not reached.

In safety evaluable patients (n=47), the median duration of study follow-up was 4.1 months (95%CI: 2.9, 5.3). Treatment-emergent adverse events (TEAEs) were 95.7%, treatment-related adverse events were 85.1%. The most common TEAEs were COVID-19 infection (40.4%; grade 1 or 2: 27.6%; grade >=3: 12.8%) and neutropenia (31.9%; grade 1or 2: 14.9%; grade >=3: 17.0%). AE related treatment discontinuation and death were reported in 2 patients, which were all due to COVID-19 pneumonia. CRS occurred in 12.8% (6/47) patients, was mild and transient. CRS in 100mg were 14.3% (2/14). All cases of CRS were grade 1 (8.5%, 4/47) or 2 (4.3%, 2/47), no grade 3 (Lee et al., ASTCT criteria), no interruptions of treatment, and no administration of Tocilizumab. The median duration of CRS was 7 hours. No ICANS were reported.

The PK profile of GB261 appeared to be linear across dose ranges tested (1mg-100mg). Effective half-life appeared to be 2-3 weeks which supports every 3-4 weeks dosing.


GB261, a novel and highly differentiated CD20/CD3 bispecific antibody, is the first clinical stage Fc+ CD20/CD3 T cell engager. In heavily pretreated B-NHL patients, GB261 showed a highly advantageous safety/efficacy balance, consistent with the MOA. The safety profile is excellent especially for the CRS which is very mild, transient and less frequent compare with other CD20/CD3 bispecific antibodies. The response after GB261 treatment was early, deep and durable. At the 100mg dose level, 80% of patients achieved CR and with favorable safety. Additionally, clinical benefit seen in other CD20/CD3 bispecific antibody failed patients provides clinical support to the unique and differentiated MOA of GB261.

Disclosures: Tan: Janssen: Research Funding; Abbvie: Research Funding; Beigene: Research Funding; Ellipses Pharma: Research Funding; Novartis: Research Funding; Gilead: Research Funding; Genor Biopharma Co. Ltd: Research Funding; Constellation Pharmaceuticals, Inc: Research Funding; Ichnos Sciences SA: Research Funding; Protagonist Therapeutics, Inc: Research Funding; Bristol-Myers Squibb: Research Funding; Qilu Pharmaceuticals Co. Ltd: Research Funding; Loxo Oncology at Lilly: Research Funding; Kartos Therapeutics: Research Funding; Shanghai EpimAb Biotherapeutics: Research Funding. Giri: Royal Adelaide Hospital: Current Employment. Guo: Genor Biopharma Co. Ltd: Current Employment. He: Genor Biopharma Co. Ltd: Current Employment. Xu: Genor Biopharma Co. Ltd: Current Employment. Li: Genor Biopharma Co. Ltd: Current Employment. Zhu: Genor Biopharma Co. Ltd: Current Employment.

*signifies non-member of ASH