december 8, 2020 - alphamab oncology (stock code: 9966 hk) announced that jiangsu alphamab biopharmaceuticals co., ltd. (“jiangsu alphamab”), a wholly-owned subsidiary of the company, has the first patient dosed in search-01 study, a potential pivotal phaseⅱclinical trial of ananti-her2 bispecific antibody kn026 in combination with a pd-l1/ctla-4 bispecific antibody kn046 (clinical trial no.: search-01/kn026-203).
search-01 trial is an open label, phaseⅱ and multi-center clinical study to evaluate the efficacy, safety and tolerability of kn026 in combination with kn046 for her2-positive solid tumors. the study is led by the principal investigator, professor lin shen from beijing cancer hospital. this study is conducted at about 40 clinical sites to enroll patients with advanced her2-positive solid tumors, covering indications of her2-positive gastric and gastroesophageal junction cancer, breast cancer, esophageal cancer, colorectal cancer, gallbladder cancer and extrahepatic cholangiocarcinoma, ovarian cancer, endometrial cancer, urothelial cancer and non-small cell lung cancer etc. the primary endpoint of the exploratory part of the study is objective response rate (orr) and duration of response (dor), and the common primary endpoint of the key clinical part is overall survival(os).
the therapeutic effect of her2 targeted therapy depends on the body's adaptive immune response. therefore, combination with immune checkpoint inhibitors such as pd-1/pd-l1 and ctla-4 can synergistically enhance the anti-tumor effect of her2 therapies. current combination studies from her2-targeted drugs and pd-1 antibodies have shown promising efficacy in her2-positive breast cancer and gastric cancer. the disease control rate, median progression-free survival and median overall survival arefar better than the historical data of toga study in gastric cancer. in an open label, multi-center study ,the combination of kn026 andkn046 demonstrated preliminary albeit promising efficacy, safety and tolerability in patients with advanced her2-expressing solid tumors who have failed standard of care treatment. among 14 her2-positive patients with evaluable efficacy, objective response rate (orr) was 64.3%, and the disease control rate (dcr) was 92.9%. the detailed data has recently been published at the annual meeting of the society for immunotherapy of cancer’s (sitc 2020).
professor lin shen from beijing cancer hospital commented “her2 positive is widely expressed in patients with multiple tumors, and there is an urgent need for an innovative treatment option that can have better & longer response, leading to improvement of the survival and quality of life. the combination therapy of anti-her2 bispecific antibody and pd-l1/ctla-4 bispecific antibody has shown a promising synergistic effect in the preliminary clinical data. we hope that the success of search-01 trial will provide her2-positive tumor patient an innovative option that is superior to the existing standard treatment, and provide a new direction for seekingher2-positive tumor treatment.”
dr. ting xu, founder, chairman and ceo of alphamab oncology, commented, “alphamab oncology is committed to continuously exploring innovative therapies for anti-tumor treatment. theirst patient dosing in thissearch-01 trial is a milestone for our endeavor to develop our core products, and rapidly advancing cutting-edge clincialresearch. we look forward the positiveoutcome of the trial, and bringing significant survival benefits to patients with her2-positive tumors. we also expect to establish the competitive advantage with theinnovative combination approachin tumor immunotherapy.”
kn026 is an anti-her2 bispecific antibody developed 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 equivalent efficacy compared with trastuzumab and pertuzumab alone or 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 phase i/ii clinical trials in china and phase i clinical trial in the united states. the results of phase i clinical trials show kn026 has excellent safety, tolerance and potentially superior anti-tumor activity in her2-positive breast cancer patients who progressed after multiple lines of anti-her2 treatment.
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 and 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. two 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 eight 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 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.
visit http://www.alphamabonc.com for more information.
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