Maxinovel announces dosing of first patient in Phase I/II study of MAX-40279 combined with KN046 in advanced solid tumor

DATA:2022/08/11

Aug11, 2022, Shanghai, China: 

Maxinovel Pharmaceuticals Co., Ltd. (“Maxinovel” hereafter) announced dosing of first patient with MAX-40279 (multi-tyrosine kinase inhibitor developed by Maxinovel)in combination with KN046 (PD-L1/CTLA-4 bispecific antibody from Alphamab Oncology [stock code: 9966.HK]) in the Phase I/II study (NCT05425602) for solid tumor, at the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.


About MAX-40279-007

This is a Phase I/II clinical trial to investigate the safety, tolerability, pharmacokinetic and efficacy of MAX-40279 in combination with KN046 in patients with advanced/metastatic solid tumors. Maxinovel and Alphamab Oncology will jointly promote the clinical development of MAX-40279/KN046 combination therapy in gastric cancer (GC) and other indications.


Previously, Maxinovel has initiated multiple dose-escalation Phase I studies in Australia and China, Phase II trials in advanced colorectal/gastric cancers in China, and a Phase I study of MAX-40279 and toripalimab (PD-1 monoclonal antibody) in collaboration with Shanghai Junshi Biosciences in solid tumors.


About MAX-40279

MAX-40279 is the first new molecular entity (NME) from Maxinovel pipeline that has progressed to proof-of-mechanism/concept stage of clinical development. It was granted orphan drug designation by the US FDA in 2018 and also supported by the Chinese National Key Grant Program for New Drug Development in 2019. Multiple Phase 1/2 clinical trials in acute myeloid leukemia (AML) and solid tumors are currently ongoing in Australia and China.

The primary mechanism of action for MAX-40279 in AML is to overcome resistance to FGFR bypass activation with FLT3 inhibitors through effective inhibition of the dual FLT3/FGFR targets. MAX-40279 also has multiple inhibitory mechanisms in solid tumors: preclinical studies have shown inhibition of multiple tyrosine kinases by MAX-40279. In addition, MAX-40279 can inhibit hematopoietic progenitor kinase 1 (HPK1) and relieve the negative regulation of HPK1 on T cell receptor (TCR) pathway. Furthermore, through translational research, Maxinovel scientists identified a potential biomarker, an adaptor protein that can bind to multiple tyrosine kinases, may be predictive of response to MAX-40279 treatment.


About KN046

KN046 is a PD-L1/CTLA-4 bispecific antibody independently developed by Alphamab Oncology. Its innovative designs include: mechanistically different CTLA-4 single domain antibody fused with PD-L1 single domain antibody; engineered to target the tumor microenvironment with high PD-L1 expression and capable of removing Treg that suppresses tumor immunity.


There are about 20 clinical trials of KN046 in different stages covering more than 10 types of tumors including NSCLC, thymic cancer, pancreatic cancer, HCC, ESCC and TNBC in Australia, US and China. The results of these clinical trials have shown an advantage in survival benefits for patients. Alphamab Oncology has received FDA clearance to enter Phase II trial of KN046 based on the clinical results in China and Australia. Moreover, the US FDA has granted KN046 to orphan drug designation for thymic epithelial tumor in September 2020. Four pivotal clinical trials are currently being conducted.



Comments from Study Team Members and Partners:


Professor Xiangdong Chen, Principle Investigator, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)


We appreciate the trust of Maxinovel to select Zhejiang Cancer Hospital as the leading site to coordinate this study. MAX-40279 is a multi-targeted tyrosine kinase inhibitor and previous clinical data in solid tumors have also demonstrated good prospect. KN046 is a PD-L1/CTLA-4 bispecific antibody and has shown generally well tolerated in clinical trials. Through the conduct of this study, we look forward to exploring the synergistic effect of novel drug combinations and providing more thoughts on the current clinical diagnosis and treatment plan for cancer patients.



Jonathan Lee, GM of WuXi Clinical, CRO

Precision immunotherapy with multi-target medicine is a direction worth exploring for oncological diseases. WuXi Clinical is hornored to participate this early trial of MAX-40279 in combination with KN046 in patients with advanced/metastatic solid tumors. I wish that through professional collaboration from our team, we will provide solid work in exploring this treatment paradigm. With the high-quality work of all partners, I expect that we will provide reliable and authentic trial aspects and results for this study, contributing soundly to the development of new medicine.


Ting Peng, Senior Medical Director of Maxinovel

MAX-40279 inhibits multiple tumor growth-associated tyrosine kinases and also has immunomodulatory effects via inhibiting HPK1 kinase. MAX-40279 monotherapy was generally well tolerated and demonstrated efficacy in early clinical studies in patients with solid tumors and hematologic malignancies. , I am curious to see whether its combination with KN046 will provide more options for patients with advanced solid tumors.



Duorui Xia, Project Manager of Maxinovel

We thank Professor Xiangdong Cheng, PI of Zhejiang Cancer Hospital and the research team for their strong support and we really appreciate the joint efforts of Maxinovel Clinical Team, CRO WuXi Clinical, SMO Clinplus, and Alphamab Oncology. We will continue to work closely, pay close attention to the safety and tolerability of the subjects in this trial.  We look forward to conducting a high-quality study in a timely fashion, handing in a satisfactory answer sheet, and ultimately bringing hope for more cancer patients.








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