● As of May 26, 2021, the disease of 22 patients with unresectable/metastatic pancreatic cancer was evaluated after at least one tumor assessment after they received the KN046 combined with chemotherapy, the objective response rate (ORR) and the disease control rate (DCR) based on RECIST was 50.0% and 95.5% respectively. The 6-month progression-free survival rate (PFS-6M Rate) was 62.3%; After 4 to 6 cycles of combo treatments, 4 patients received tumor resection only after the MDT team agreed that they meet the requirements for surgery.
● The Phase III pivotal clinical study of KN046 combined with chemotherapy for the first-line treatment of pancreatic cancer will be launched soon.
Suzhou, China, September 27, 2021 - Alphamab Oncology (stock code: 9966 HK) announced that, the updated data of the Phase II clinical study (KN046-IST-04) of KN046 combined with nab-paclitaxel/gemcitabine for the first-line treatment of pancreatic ductal adenocarcinoma (PDAC) were presented at the 24th Annual Meeting of Chinese Society of Clinical Oncology (CSCO). The e-Poster is available from the company's website www.qqkjdm.cn.
KN046-IST-04 is an investigator-initiated Phase II clinical study conducted in China, and enrolled patients with histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), who have ECOG PS of 0-1 and never received prior systemic anti-tumor treatment. KN046 (5mg/kg, Q2W) plus nab-paclitaxel (125mg/m2, D1, 8, 15, Q4W) and gemcitabine (1000mg/m2, D1, 8, 15, Q4W) were administered for 4-6 cycles followed by KN046 (5mpk) maintenance therapy every 2 weeks. Tumor response was assessed according to RECIST 1.1 every 8 weeks. The primary endpoint is investigator-assessed ORR, and the secondary endpoints are DCR, DOR, TTP, PFS, OS and safety.
Primary results from this study were first published at ASCO 2021. This updated data included more evaluable patients and further confirmed the ORR was double than with standard chemotherapy.
As of May 26, 2021, 29 patients with median age 57 (36-75) years were enrolled, and 20 patients (69.0%) are still under treatment. 17 out of 29 patients (58.6%) had distant metastases at baseline. Median KN046 exposure time was 14.1 (2.0, 52.7) weeks.
Of 22 patients who underwent at least one tumor assessment, 4.5% (1/22) patients achieved complete response (CR), 45.5% (10/22) achieved partial response (PR), and 45.5% (10 /22) had stable disease (SD); the ORR was 50.0% (95% CI: 28.2%, 71.8%), and the DCR was 95.5% (95% CI: 77.2%, 99.9%). After 4 to 6 cycles of treatment, 4 patients who achieved partial remission (PR) received resection when the MDT team assessed that they meet the requirements for surgery. The 6-month progression-free survival (6M-PFS) rate was 62.3% (95% CI: 30.4%, 82.9%).
29 patients were included in the safety analysis population. The TRAE of KN046 was 55.2%, and 27.6% patients had grade ≥3 TRAE. Grade ≥3 irAE occurred in three patients (10.3%), which were rash and infusion reaction, autoimmune hepatitis, and aspartate aminotransferase increased. 1 patient experienced SAE with KN046 and 2 patients discontinued treatment due to the AEs. No AEs leading to death occurred.
Professor Gang Jin, First Affiliated Hospital of Naval Military Medical University (Changhai Hospital of Shanghai), commented, “Pancreatic cancer is one of the most malignant tumor types to affect the digestive system, which is difficult to diagnose or treat. About 90-95% histopathology types of pancreatic cancer are adenocarcinomas. Due to the rapid progression and high mortality rate, the 5-year survival rate of pancreatic cancer is only 3%-5%. Alphamab’s bispecific antibody KN046 combined with nab-paclitaxel plus gemcitabine (AG) chemo regimen achieved a double ORR than the historical ORR report of AG regimen, and this is very encouraging. We believe that KN046 combined chemotherapy could become a breakthrough therapy for the first-line pancreatic cancer. We are looking forward to the follow-up research and development.”
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, thymic cancer, pancreatic cancer, HCC, ESCC and TNBC 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 pivotal clinical trials are currently being conducted.
About Alphamab Oncology
Alphamab Oncology is focusing on innovation, production and commercialization of anti-tumor drugs. 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 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.
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