Alphamab Oncology announced that data from the Phase II clinical study of the PD-L1/CTLA-4 bispecific antibody KN046 combined with platinum doublet chemotherapy for the treatment of patients with advanced non-small cell lung cancer (NSCLC) is presented in a poster session at the ASCO 2021(2021 American Society of Clinical Oncology Annual Meeting). 

Topic: A Phase 2, Open-Label, Multi-Center Study to evaluate the efficacy, safety, and tolerability of KN046 in combination with chemotherapy in subjects with advanced non-small cell lung cancer
Poster number: 200614
Session Title: Lung Cancer-Metastatic Non-Small Cell Lung Cancer
First author: Professor Yunpeng Yang, PhD, Sun Yat-sen University Cancer Center

KN046-202 (NCT04054531) is a phase II, open-label, multi-center clinical study to evaluate the efficacy, safety and tolerability of KN046 combined with platinum doublet chemotherapy in patients with advanced non-small cell lung cancer. The results show that KN046 combined with platinum doublet chemotherapy is well tolerated and has shown promising clinical benefit as IL treatment for stage IV NSCLC particularly in PD-L1≥1% tumors and squamous histology. The progression-free survival (PFS) and overall survival (OS)were longer than usually seen in this population. Similar survival was observed in patients with PD-L1≥1% and PD-L1<1%.

As of January 19, 2021, 87 patients with advanced NSCLC who had not received systemic treatment were enrolled, including 51 patients with non-squamous NSCLC and 36 patients with squamous NSCLC. 46 patients PD-L1≥1%, and 37 patients PD-L1<1%. The median treatment duration of KN046 was 21 weeks.

In 81 efficacy evaluable patients, the objective response rate (ORR) was 50.6% (95% CI: 39.3%, 61.9%), and the disease control rate (DCR) was 87.7% (95% CI: 78.5%,93.9%). In patients with non-squamous NSCLC, the objective response rate (ORR) and disease control rate (DCR) were 45.8% (95% CI: 31.4%, 60.8%) and 89.6% (95% CI: 77.3%, 96.5%) respectively. In patients with squamous NSCLC, the objective response rate (ORR) and disease control rate (DCR) were 57.6% (95% CI: 39.2%, 74.5%) and 84.8% (95% CI: 68.1%, 94.9) respectively.

The median progression-free survival (mPFS) is 5.9 months (95% CI: 5.3, 8.7), and the median overall survival (OS) was not reached; OS rate at 12 and 15 months were both 74.9%.; Similar OS curves have been observed in PD-L1 ≥1% and PD-L1<1% patients. In PD-L1 ≥1% patients, the median PFS is 6.7 months, and 10.8 months for PD-L1 ≥1% squamous NSCLC patients.

22 patients (25.3%) experienced Grade≥3 treatment-related adverse events (TRAE). The most common TRAEs were diarrhea (5.7%), alanine aminotransferase increased (4.6%), infusion related reaction (3.4 %), rash (3.4%) and aspartate aminotransferase increased, dermatitis allergic and immune-mediated pneumonitis (2.3%, respectively). Adverse events are manageable.

Professor Zhang Li from Sun Yat-sen University Cancer Center, the principal investigator, commented, "Lung cancer is the malignant tumor with the highest incidence and mortality in China. In recent years, immunotherapy has significantly improved the long-term survival of patients with advanced NSCLC. However, the overall prognosis and long-term efficacy still need to be improved. We are very pleased to see that Alphamab Oncology's bispecific antibody KN046 demonstrates clinical benefit such as ORR, PFS and OS, which means that patients with advanced NSCLC may get better treatment options. We look forward to further results of KN046 as a first-line treatment in follow-up studies."

Dr. Ting Xu, Chairman and CEO of Alphamab Oncology commented, "In recent years, immunotherapies have radically improved treatment for non-small cell lung cancer (NSCLC) patients. Alphamab Oncology has conducted a number of clinical studies to explore innovative and better treatment options focusing on the post-PD-1 era. KN046 showed good tolerability, safety and efficacy in the phase II study for the first-line treatment of patients with advanced squamous -NSCLC or non-squamous NSCLC. Phase III clinical study of KN046 combined with chemotherapy for the treatment of squamous NSCLC is ongoing, and the first interim analysis expected to be available by the end of 2021. This is the world's first phase III clinical study of a PD-L1/CTLA-4 bispecific antibody. We hope that the results of this study will change the treatment patterns for advanced NSCLC and bring new options for global lung cancer patients."

About KN046

KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Jiangsu Alphamab. Its innovative designs include: a different mechanism CTLA-4 fused with PD-L1 single domain antibody; engineered to target the tumor microenvironment with high PD-L1 expression, and Treg（suppress tumor immunity） clearing function.

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

About Alphamab Oncology

Alphamab Oncology is a biopharmaceutical company and a medical equipment company, focusing on innovative biologics medicine for oncology. On December 12, 2019, the Company was listed in the mainboard of Hong Kong, S.A.R., China Stock Exchange with stock code 9966.

Alphamab has fully integrated proprietary biologics platforms in bi-specifics and protein engineering. Its highly differentiated in-house pipeline includes fifteen tumor monoclonal antibodies and bispecific antibodies and a Covid-19 multifunctional antibody. Four products have advanced into phase I-III clinical trials or pre-marketing stage in China, the United States, Japan and Australia. The BLA for Envafolimab (KN035) has been accepted and granted Priority Review by the National Medical Products Administration (NMPA).

The Company also has state-of-the-art manufacturing capabilities designed and built to meet NMPA and EU/FDA's cGMP standards and a complete quality system which has passed the on-site inspection of a European Union qualified person. Alphamab Oncology is committed to building a global leading, multi-dimensional drug development and commercialization platform, focusing on multifunctional biological innovative drugs, and to benefit patients in China and around the world.