● KN046 in combination with Lenvatinib in 1st line HCC achieved 57% and 76% ORR and 95% and 95% DCR by RECISCT 1.1 and imRECIST, respectively.
● Based on the promising data of this Phase II study, a global phase III clinical study of KN046 in combination with Lenvatinib for the first line treatment of hepatocellular carcinoma is justified and currently in the planning phase.
Suzhou, Sep 17, 2021 - Alphamab Oncology (stock code: 9966.HK) announced that data from a Phase II study (KN046-IST-05) of KN046 in combination with lenvatinib as first-line treatment for hepatocellular carcinoma (HCC) were presented as Poster at the ESMO (European Society for Medical Oncology) congress 2021.
Liver cancer is one of the most common malignant tumors in Asia and very rare in the Western world. The new cases and deaths in China account for nearly 50% of the world’s total due to the high infection rate of hepatitis B virus, making it the second most fatal tumor in China. The prognosis of liver cancer in China is generally poor, with a 5-year survival rate of only 12.1%，and for advanced liver cancer, the 5-year survival rate is less than 5%. Immune checkpoint inhibitors combined with anti-VEGFR therapy have become popular in the treatment of liver cancer. The preliminary results of KN046 combined with lenvatinib in the first-line treatment of liver cancer， have been presented as Poster at the ESMO congress on September 16, 2021. The e-Poster is available from the company's website www.qqkjdm.cn.
Title: KN046 (an anti-PD-L1/CTLA-4 Bispecific Antibody) in combination with Lenvatinib in the treatment for advanced unresectable or metastatic hepatocellular carcinoma (HCC): preliminary efficacy and safety results of a prospective phase II trial
Poster number: 938P
First author: Professor Bao-cai Xing, Beijing Cancer Hospital
This phase II clinical study in China enrolled patients with histologically or cytologically confirmed unresectable locally advanced or metastatic HCC who had not received first-line treatment. The Pts with BCLC stage B or C had received Lenvatinib 12 mg/day (bodyweight [BW] ≥60 kg) or 8 mg/day (BW<60 kg) orally and KN046 5 mg/kg Q3W IV on Day 1 of a 21-day cycle until disease progression or intolerable toxicity or 2 years. The Primary endpoints were safety and ORR by RECIST v1.1 per investigators.
As of cutoff date of April 8th, 2021, 25 enrolled pts received combination treatment with median duration of 10 weeks, and 21 pts (84%) were in BCLC stage C. For 21 evaluable pts, ORR was 57% (95% CI 34.0%-78.2%) and DCR was 95% (95% CI 76.2%-99.9%) by RECIST v1.1 or imRECIST. When evaluated by mRECIST, ORR was improved to 76.2% (95% CI 52.8%-91.8%) and DCR was 95% (95% CI 76.2%-99.9%). Treatment-emergent adverse events (TEAEs) occurred in 64% of pts, 20% of which was ≥grade 3. The incidence of TEAE related with KN046 was 60% (n=15), 8% of which was ≥grade 3, including pneumonitis (n=1, 4.0%) and platelet count decreased (n=1, 4.0%).
Professor Baocai Xing from Beijing Cancer Hospital, the principal investigator of the clinical trial, commented, “Liver cancer is the second most common malignant tumor in China, and most patients are diagnosed in advanced stages with low survival rates and poor prognosis. In the past, surgery and locoregional therapy were the main treatments for liver cancer. In 2019, study on combined immunotherapy and targeted therapy for advanced liver cancer showed promising data, starting a new era of systematic treatment. However, the ORR was only about 30%, and patients are still looking forward to new therapies with better outcomes. The single-arm phase II study of KN046 combined with lenvatinib initiated by Beijing Cancer Hospital showed higher ORR exceeded 50%, which significantly improved the overall response, and could provide a greater chance for transformation treatment, prolonging the survival of patients with advanced HCC.
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 registrational clinical trials are currently being conducted.
About Alphamab Oncology
Alphamab Oncology is a biopharmaceutical company focusing on innovative biologics medicine for oncology. 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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