Alphamab Oncology announced data from Phase 2 clinical study (KN046-204) of KN046(PD-L1/CTLA-4 bispecific antibody) plus paclitaxel/cisplatin for the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) is presented in a poster session at the ASCO 2021 (2021 American Society of Clinical Oncology Annual Meeting).

Esophageal cancer is one of the most common malignant tumors in the world. According to data released by GLOBOCAN 2020, approximately 320,000 new cases occurred in China in 2020, accounting for half of the global new cases, of which esophageal squamous cell carcinoma (ESCC) is the main subtype (90%-95%). The prognosis of esophageal cancer is very poor, with only about 20% overall 5-year survival rate and 3.5% 5-year survival rate for metastatic patients. There is a huge unmet clinical need. KN046-204 is a phase II clinical study in China to evaluate the efficacy and safety of KN046 monotherapy or plus chemotherapy for unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

KN046-204 included 3 cohorts. In cohort 3, which is reported here, systemic treatment na?ve patients (ECOG PS of 0-1) with unresectable locally advanced, recurrent or metastatic ESCC were enrolled and treated with KN046 in combination with paclitaxel and cisplatin for 4~6 cycles during initial therapy. For those without progressive disease, maintenance treatment was administrated with KN046 monotherapy (5mpk, iv, q2w) until progression or unacceptable toxicity. Tumor response was assessed according to RECIST 1.1 every 6 weeks. The primary endpoint was investigator-assessed ORR. Secondary endpoints included DCR, safety, PK profile, and immunogenicity.

As of January 14, 2021, 15 patients were enrolled in cohort 3, all of whom were male, 52.3% ≥ 60 years of age, 64% ECOG 1, and 80% with distant metastasis. Median exposure time to KN046 was 11.4 weeks, and average KN046 treatment was 2.4 cycles. 12 subjects were included in the efficacy analysis, and the objective response rate (ORR) was 58.3%, and the disease control rate (DCR) was 91.6%. 7 patients (58.3%) had partial response (PR), including one complete response of target lesion. 4 patients (33.3%) had stable disease (SD) with 3 pts showing more than 20% of tumor burden reduction.  15 subjects were included in the safety analysis. The overall incidence of treatment related adverse events (TRAE) was 80.0%, with 13.3% Grade 3 or above. Infusion-related adverse events occurred during 7.8% and most were mild. Immune related adverse events（irAE）were seen in 53.3% and the most common ≥Grade 3 irAE were nausea (n=1, 6.7%) and rash (n=1, 6.7%).

Professor Jianming Xu from Chinese People's Liberation Army General Hospital, the principal investigator, commented, "Esophageal cancer usually begins in the cells that line the inside of the esophagus. The most common types of esophageal cancer are adenocarcinoma and squamous cell carcinoma. It is one of the most common malignant tumors in China, and about 90% are squamous cell carcinoma (ESCC). In recent years, immunotherapy has become the standard treatment for second line therapy in patients with esophageal cancer. However, the prognosis for patients with advanced ESCC is still poor. In KN046-204 study, KN046 has shown positive efficacy and safety data for the first-line treatment of patients with advanced ESCC, and a better treatment option may become available for patients in need."

Dr. Johannes Nippgen, Chief Medical Officer of Alphamab Oncology commented, "We are very pleased to see that in cohort 3, KN046 in combination with paclitaxel and cisplatin as first-line treatment for patients with ESCC showed an ORR of 58.3% and DCR of 91.6% with a good safety profile. In an investigator initiated study, KN046 plus chemo-radiation therapy in recurrent and metastatic ESCC patients also showed an ORR of 44.4% and a DCR of 94.4%. With these positive results, we believe KN046 would help address this huge unmet clinical need of ESCC patients in future."

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 supply 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 an 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.