Preclinical characterization and phase 1 results of ADG106 in patients with advanced solid tumors and non-Hodgkin's lymphoma

Yuxiang Ma; Fan Luo; Yang Zhang; Qianwen Liu; Jinhui Xue; Yan Huang; Yuanyuan Zhao; Yunpeng Yang; Wenfeng Fang; Ting Zhou; Gang Chen; Jiaxin Cao; Qun Chen; Xiaohong She; Peter Luo; Guizhong Liu; Li Zhang; Hongyun Zhao

doi:10.1016/j.xcrm.2024.101414

Preclinical characterization and phase 1 results of ADG106 in patients with advanced solid tumors and non-Hodgkin's lymphoma

Cell Rep Med. 2024 Feb 20;5(2):101414. doi: 10.1016/j.xcrm.2024.101414. Epub 2024 Feb 7.

Authors

Yuxiang Ma¹, Fan Luo², Yang Zhang¹, Qianwen Liu¹, Jinhui Xue¹, Yan Huang³, Yuanyuan Zhao³, Yunpeng Yang³, Wenfeng Fang³, Ting Zhou³, Gang Chen³, Jiaxin Cao⁴, Qun Chen¹, Xiaohong She⁵, Peter Luo⁵, Guizhong Liu⁵, Li Zhang⁶, Hongyun Zhao⁷

Affiliations

¹ Department of Clinical Research, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
² Department of Intensive Care Unit, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
³ Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
⁴ Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China.
⁵ Adagene, Inc., San Diego, CA, USA.
⁶ Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China. Electronic address: zhangli@sysucc.org.cn.
⁷ Department of Clinical Research, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China. Electronic address: zhaohy@sysucc.org.cn.

Abstract

ADG106, a ligand-blocking agonistic antibody targeting CD137 (4-1BB), exhibits promising results in preclinical studies, demonstrating tumor suppression in various animal models and showing a balanced profile between safety and efficacy. This phase 1 study enrolls 62 patients with advanced malignancies, revealing favorable tolerability up to the 5.0 mg/kg dose level. Dose-limiting toxicity occurs in only one patient (6.3%) at 10.0 mg/kg, resulting in grade 4 neutropenia. The most frequent treatment-related adverse events include leukopenia (22.6%), neutropenia (22.6%), elevated alanine aminotransferase (22.6%), rash (21.0%), itching (17.7%), and elevated aspartate aminotransferase (17.7%). The overall disease control rates are 47.1% for advanced solid tumors and 54.5% for non-Hodgkin's lymphoma. Circulating biomarkers suggest target engagement by ADG106 and immune modulation of circulating T, B, and natural killer cells and cytokines interferon γ and interleukin-6, which may affect the probability of clinical efficacy. ADG106 has a manageable safety profile and preliminary anti-tumor efficacy in patients with advanced cancers (this study was registered at ClinicalTrials.gov: NCT03802955).

Keywords: ADG106; CD137/4-1BB; non-Hodgkin’s lymphoma; phase 1 trial; preclinical study; solid tumors.

Publication types

Clinical Trial, Phase I

MeSH terms

Antibodies, Monoclonal
Humans
Lymphoma, Non-Hodgkin* / drug therapy
Neoplasms*
Neutropenia*
Treatment Outcome

Substances

Antibodies, Monoclonal

Associated data

ClinicalTrials.gov/NCT03802955