As of January 30, 2022,31 patients with HER2-positive unresectable locally advanced or metastatic GC/GEJ, with no prior systemic treatment, were enrolled. 27 patients were evaluable for efficacy. The ORR was 77.8% and DCR was 92.6%. The phase III pivotal study is planned to confirm the efficacy and safety of KN026/KN046 combo as the 1st line treatment for Her2 positive GC/GEJ patients
SUZHOU, China, Sept. 14, 2022 /PRNewswire/ — Alphamab Oncology (stock code: 9966.HK) announced that data from the phase II clinical study of the chemo-free regimen of KN026 in combination with KN046 (KN026-203) were presented as a Poster at the ESMO Congress 2022 (ESMO 2022).
Title: The preliminary efficacy and safety of KN026 combined with KN046 treatment in HER2-positive locally advanced unresectable or metastatic gastric/gastroesophageal junction cancer without prior systemic treatment in a phase II study
Poster Number: 1210P
First author: Lin Shen, Prof, Beijing Cancer Hospital
KN026-203 is an open-label, multi-center, phase II clinical study to evaluate the efficacy and safety of KN026 in combination with KN046 in the treatment of HER2-positive solid tumors. Total 102 patients were enrolled in the study, including HER2-positive GC/GEJ, breast cancer and other HER2-positive solid tumors. Patients received KN046 (iv.5mg/kg Q3W) plus KN026 (iv.30mg/kg Q3W, loading on C1D1, D8) treatment until progression or unacceptable toxicity. The primary endpoint was confirmed ORR assessed by the investigator every 6 weeks（RECIST v1.1）.
As of 30 Jan 2022, a total of 31 HER2 positive locally advanced unresectable or metastatic GC/GEJ patients without prior systemic treatment were enrolled. The median age was 64 years old, with 14 patients (45.2%) aged ≥ 65 years. 26 patients (83.9%) were HER2 IHC 3+ and the others (16.1%) were HER2 IHC 2+ with HER2 gene amplification. 25 patients (80.6%) were ECOG 1. 19 patients (61.3%) had liver metastasis, and 4 patients (12.9%) had lung metastasis.
27 patients were evaluable for efficacy. The ORR was up to 77.8% (95% CI: 57.7, 91.4), and the DCR was 92.6% (95% CI: 75.7, 99.1).
In terms of safety, the most common (≥10%) TRAEs were diarrhea (32.3%), pyrexia (32.3%), leukopenia (22.6%), neutropenia (16.1%), infusion related reaction (16.1%), hypothyroidism (16.1%), ALT increased (12.9%), direct bilirubin increased (12.9%) and rash (12.9%). The majority of the AEs were grade 1 or 2 in severity. Only 5 patients (16.1%) experienced ≥ Gr3 TRAEs. There was no treatment related death.
Professor Shen Lin from Peking University Cancer Hospital, the principal investigator, commented: “The incidence of gastric cancer remain high in China, accounted for about half in the whole world. 10%-20% of gastric cancer patients were HER2 positive. For those patients trastuzumab combined with chemotherapy is the standard first-line treatment. Here, we are very pleased to see that KN026 combined with KN046, a chemo-free regimen showed excellent efficacy in 1st line HER2-positive gastric cancer, with ORR as high as 77.8%. Compared with chemo containing therapy, KN026/KN046combo also showed favorable safety profiles. We look forward to further exploring the great value of this chemo-free regimen in HER2-positive gastric cancer in subsequent clinical studies, so as to provide new and better options for patients with HER2-positive gastric cancer to improve their quality of life.”
KN026 is an anti-HER2 bispecific antibody invented by Alphamab Oncology using the proprietary Fc-based heterodimer bispecific platform technology called CRIB (Charge Repulsion Induced Bispecific). KN026 can bind two non-overlapping epitopes of HER2 simultaneously, leading to a dual HER2 signal blockade. KN026 has demonstrated potentially superior efficacy to Trastuzumab and Pertuzumab in combination, such as increased binding affinity, as well as better tumor inhibition in HER2-positive tumor cell lines. Additionally, KN026 has also shown inhibitory effect on tumor cells with medium or low HER2 expression or Trastuzumab-resistant cell lines.
KN026 received IND approval from the National Medical Products Administration (NMPA) of China and U.S. Food and Drug Administration (FDA) in 2018. Currently, it is in multiple clinical trials in China and the United States, for patients with breast cancer, or gastric cancer/gastroesophageal junction cancer, etc. Two phase III pivotal studies of KN026 combined with chemotherapy and the chemo-free regimen of KN026/KN046 combo for the treatment of gastric cancer are ongoing. The results of prior clinical studies showed that KN026 has good efficacy and safety profiles, even in heavily pretreated patients with HER2-positive breast cancer.
KN046 is PD-L1/CTLA-4 bispecific antibody independently developed by Jiangsu Alphamab. Its innovative designs include: a novel 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 more than 20 clinical trials of KN046 in different stages covering more than 10 types of tumors including NSCLC, pancreatic cancer, thymic cancer, HCC, ESCC and TNBC in Australia, the US and China. The results of these clinical trials have shown an advantage in survival for patients. Alphamab Oncology 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, and Among them, the interim analysis of the phase III clinical study of KN046 combined with chemotherapy in the first-line treatment of non-small cell lung cancer successfully reached the preset PFS endpoint.
About Alphamab Oncology
Alphamab Oncology is focusing on innovation, including discovery, development, 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 a fully integrated proprietary biologics platforms in bi-specifics and protein engineering. Its highly differentiated in-house pipeline consists of tumor monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates. Six products have advanced into phase I-III clinical trials in China, the United States, Japan and Australia and in November 2021, one of these products, the unique PD-L1 antibody for subcutaneous administration, Envafolimab, received marketing authorization from the Chinese National Medical Products Administration (NMPA) for the treatment of previously treated MSI-H/dMMR advanced solid tumors.
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.