September 20, 2020, Beijing, China – 3D Medicines announced the publication of "the results of a single arm, pivotal, multicenter, phase II study to evaluate the efficacy and safety of Envafolimab (KN035) monotherapy in dMMR/MSI-H advanced cancer" on Chinese Society of Clinical Oncology (CSCO) annual meeting. Envafolimab (KN035) is a next-generation PD-L1 antibody, on which 3D Medicines Inc., Jiangsu Alphamab Biopharmaceuticals Co., Ltd. and Simcere Pharmaceuticals reached a strategic collaboration. The research was led by Professor SHEN Lin from Beijing Cancer Hospital and was awarded "excellent paper of CSCO" this year.

Title

A single arm, pivotal, multicenter, phase II study to evaluate the efficacy and safety of Envafolimab (KN035) monotherapy in MSI-H/dMMR advanced tumors.

Methods

The clinical trial is a single arm, pivotal, multicenter study of Envafolimab (KN035) in subjects with previously treated MSI-H/dMMR advanced cancer. The primary endpoint is the objective response rate (ORR) per RECIST v1.1 by Blinded Independent Review Committee (BIRC), and the second endpoints include duration of response (DoR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). MSI-H/dMMR status was assessed centrally for colorectal cancer (CRC) and gastric cancer (GC) and locally for other tumors.

Results

As of June 19, 2020, the cut-off date of the data published, 103 subjects with MSIH/dMMR advanced cancers have been enrolled. The overall population (n=103) included 65 CRC patients previously treated with second-line or third-line treatment, 18 GC patients treated with first-line or later lines of treatment, and 20 other tumor patients treated with first-line or later lines of treatment, with a median follow-up of 11.5 months. The follow-up time of the last patient enrolled was 6.5 months. Among the 103 subjects, 55 have withdrawn from the study, and disease progression was the main reason (67.3%).

Main Highlights

1. Envafolimab (KN035) monotherapy has demonstrated significant and durable efficacy in advanced solid tumor patients who have failed first-line or later lines of treatment, showing its advantages over current treatment options and comparable efficacy to similar products:
 

·Confirmed ORR per BIRC were 43.1%, 44.4%, 40.0% and 42.7% in advanced CRC patients, advanced GC patients, other solid tumor patients and overall population, respectively.

·Median DoR was not reached.

·Median OS was not reached, and the 12-month OS rate were 72.9%, 83.3%, 75.0% and 74.6% in advanced CRC patients, advanced GC patients, other solid tumor patients and overall population, respectively.

2. Envafolimab (KN035) demonstrated favorable tolerability and safety profile, with the incidence of grade 3-4 treatment-related adverse events (TRAEs) as low as 15.5%.
 

3. Envafolimab (KN035) was administered via subcutaneous injection. No infusion reactions were observed and the incidence of injection site reactions was low.

4. Grade 3-4 drug-related treatment emergent adverse events (TEAEs) were observed in 16 patients (15.5%), and no grade 5 drug-related TEAEs was reported. 2.9% of the subjects stopped the medication because of drug-related TEAEs, and the incidence and details of immune-related adverse events (irAEs) were comparable to similar products. No immune-related pneumonitis or colitis was reported, and no infusion reactions occurred. Injection site reactions were observed in 6 (5.8%) subjects (all grade 1-2) without drug-related serious TEAEs or stop of medication reported.

Conclusions

The data support Envafolimab (KN035) as a new promising and convenient treatment option with durable benefit for advanced MSI-H/dMMR cancer patients who have failed first-line or later lines of treatment.

References

A single arm, pivotal, multicenter, phase 2 study to evaluate efficacy and safety of Envafolimab (KN035) monotherapy in dMMR/MSI-H advanced cancer, 2020, CSCO Annual Meeting.

About Envafolimab

Envafolimab (KN035) is a PD-L1 single-domain antibody Fc fusion protein independently invented by Alphamab. Based on the unique design, Envafolimab (KN035) has advantages in safety, convenience and compliance, and can be used for the patients who are not suitable for intravenous infusion with a lower medical cost. In February, 2016, 3D Medicines and Alphamab signed a collaborative development agreement. Alphamab, as the original research party, is responsible for production and quality, and 3D Medicines is responsible for global clinical development in the field of oncology, registration, global market development and commercialization. On March 30, 2020, Alphamab, 3D Medicines and Simcere reached a three-way strategic collaboration, and Simcere is responsible for the exclusive commercial promotion of the product in mainland China. At present, Envafolimab (KN035) has been simultaneously tested in clinical trials for multiple cancer indications in China, the United States and Japan, and the research for multiple indications have entered the registration/ clinical Phase III. Envafolimab (KN035) has been awarded Orphan Drug Designation by FDA, and the marketing application to NMPA is planned to be submitted in 2020.

About 3D Medicines

3D Medicines, Inc. is a clinical-stage biopharmaceutical company with a mission to help people with cancer live longer and better. Envisioning a future when cancer is managed as a chronic disease, 3D Medicines focuses on the development of differentiated next-generation immuno-oncology drugs, helping cancer patients live with prolonged survival time and a better quality of life. 3D Medicines has established a pipeline with both next-generation biological macromolecule and chemotherapeutic small-molecule drugs, as well as a professional team capable of global development, registration and commercialization operation.

About Alphamab Oncology

Alphamab Oncology is a biopharmaceutical company focusing on the research and development, manufacturing and commercialization of biologics for oncology. On December 12, 2019, the Company was listed in the mainboard of Hong Kong Stock Exchange with stock code 9966.

Alphamab has fully integrated proprietary biologics platform in bi-specifics and protein engineering. Its highly differentiated in-house pipeline consists of eight anti-cancer drug candidates, four of which have advanced into Phase I – III clinical development phases in China, US and Japan. 

The Company also has proprietary CRIB and CRAM platforms for bi-specifics and antibody mixtures, and state-of-the-art manufacturing capability designed and built to meet NMPA and EU/FDA’s cGMP standards. With multiple in-house proprietary platforms for innovative biopharmaceuticals, Alphamab Oncology has built a robust pipeline in oncology/immunology to benefit cancer patients around the world.

About Simcere

Simcere is a research and development-driven Chinese pharmaceutical company with a State Key Lab for Translational Medicine and Innovative Drug Development. It is committed to delivering highly effective treatment to patients. Simcere achieves this by focusing its efforts on therapeutic areas of oncology, neurology, inflammation/immunology diseases and more. By leveraging its commercial capability, all of the company’s best products have achieved leading market shares in China. Simcere continues to promote the advancement of international scientific and medical breakthroughs through a collaborative R&D strategy and extensive strategic partnership with several multinational companies.
 

Note: (1) The clinical development, registration and commercialization of soft tissue sarcoma in North America is led by Tracon