Alphamab Oncology announced that data from a Phase II study (KN046-IST-04) of KN046 plus nab-paclitaxel/gemcitabine as first-line treatment for pancreatic ductal adenocarcinoma (PDAC) was presented in a poster session at the ASCO 2021(2021 American Society of Clinical Oncology Annual Meeting).

Pancreatic cancer is known as "the king of cancer". Pancreatic adenocarcinoma is the most common type of pancreatic cancer (about 90%), which is difficult to diagnose, progresses quickly with poor prognosis. Most patients have disease that is surgically incurable at the time of clinical presentation, and there is an urgent unmet clinical need. KN046-IST-04 is an investigator-initiated Phase II clinical study conducted in China. The preliminary results of the study (as of January 15, 2021) have been presented in a Poster session at the ASCO 2021 virtual annual meeting on June 4 (EST). 

This ongoing phase II clinical study in China enrolled patients with histologically or cytologically confirmed unresectable locally advanced or metastatic PDAC who have ECOG PS of 0-1 and never received systemic anti-tumor therapy for advanced or metastatic diseases.  KN046 plus nab-paclitaxel and gemcitabine were administered 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. Secondary endpoints are DCR, DOR, TTP, PFS, OS and safety.

As of January 15, 2021, 17 patients were enrolled, median age (range) was 56 (36-75) years, 9 patients ECOG 1, and 7 patients had liver metastases. Median KN046 exposure time was 9.5 weeks. 9 patients were included in the efficacy analysis and 17 patients in the safety analysis. In best overall response assessment, there were 55.6% PR (5/9) and 33.3% SD (3/9). ORR was 55.6% (95% CI: 21.2~86.3), and DCR was 88.9% (95% CI: 51.8~99.7).  The incidence of treatment-related adverse events (TRAE) was 64.7%, with 29.4% grade 3 TRAE. The most common (≥10%) TRAEs were: alanine aminotransferase increased (n=5, 29.4%), nausea (n=3, 17.6%), rash (n=3, 17.6%), aspartate aminotransferase increased (n=2, 11.8%), diarrhoea (n=2, 11.8%), hyperphosphataemia (n=2, 11.8%), pyrexia (n=2, 11.8%), vomiting (n=2, 11.8%).

Professor Gang Jin from Changhai Hospital of Shanghai, the principal investigator of the clinical trial, commented, "Pancreatic cancer is one of the prevalent malignant tumors in China, which is highly aggressive with extremely poor prognosis. There is a trend towards an increase of pancreatic cancer incidence (+31.6%) and mortality (+43.5%) in China from 2015 to 2020。 The number of new diagnoses almost equals the number of deaths, and there is an urgent unmet clinical need. Nab-paclitaxel plus gemcitabine has been recommended by international guidelines for first-line treatment of advanced PDAC but chemoresistance is difficult to avoid. Combination of immune checkpoint inhibitors (ICIs) and chemotherapy has demonstrated substantial promise  for the treatment of pancreatic cancer. We are very pleased to see that PD-L1/CTLA-4 bispecific antibody KN046 plus nab-paclitaxel/gemcitabine showed an objective response rate of 55.6% in patients with advanced pancreatic ductal adenocarcinoma, which more than doubles the ORR reported for patients with nab-paclitaxel plus gemcitabine. We look forward to exploring KN046 potential value in follow-up clinical studies and bring new options for patients with advanced pancreatic cancer."

Dr. Ting Xu, Chairman and CEO of Alphamab Oncology commented, "We are very pleased to see that KN046 shows promising data in the KN046-IST-04 study for the treatment of pancreatic cancer, once again proves the huge potential value that this innovative candidate can bring. Thanks to the experts, study team and patients who made this study possible. The updated results from this clinical study with more patients included in the efficacy analysis will be presented at an upcoming medical meeting. Based on these data, a phase III pivotal clinical study of KN046 in combination with chemotherapy for the first line treatment of pancreatic cancer is planned to be launched this year to further evaluate the efficacy, with the aim of bringing this potential new treatment option to people in need as soon as possible."

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 and supplies 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.