november 10, 2020 - alphamab oncology (stock code: 9966.hk) today announced the combination therapy of kn026 (a recombinant humanized anti-her2 bispecific antibody) plus kn046 (a recombinant humanized pd-l1/ctla-4 bispecific antibody), both independently invented by jiangsu alphamab biopharmaceuticals co., ltd. (“alphamab”), a wholly-owned subsidiary of the company, has achieved preliminary favorable results in the phase ib trial. the clinical data is presented at the 35th anniversary annual meeting of the society for immunotherapy of cancer (sitc 2020). the e-poster is simultaneously published on the company website.
the annual meeting of the society for immunotherapy of cancer (sitc) is the world's largest international event dedicated to cancer immunotherapy, and brings together thousands of international industry leaders and representatives from academia, regulatory agencies and government agencies to participate and exchange ideas. due to the covid-19 pandemic, the sitc 2020 will be held online. alphamab oncology’s e-poster will be presented in the online virtual hall from 9:00 am to 5:00 pm on november 11-14, us eastern time. (abstract link: ).
preliminary safety, tolerability and efficacy results of kn026 in combination with kn046 in patients with her2 aberrated solid tumors
presentation format: e-poster
abstract no.: 810
reporter: beijing cancer hospital, professor jifang gong
e-poster presentation time: november 11, 2020 at 9:00 am (us eastern time)
this report is about a dose-escalation and dose-expansion, open label, multi-center clinical study that enrolled patients with advanced her2-expressing solid tumors and have failed the standard of care treatment. as of september 8, 2020, a total of 25 patients with gastrointestinal cancer were enrolled and received three dose levels of kn026 and kn046 combination therapy. kn026 and kn046 combination therapy was well tolerated and no dose-limiting toxicity was observed. the incidence of treatment-related adverse events of grade 3 and above was around 23% to 24%. common treatment-related adverse events include infusion-related reactions, anemia, white blood cell count decreased, diarrhea, transaminases increased, and platelet count decreased.
the efficacy was evaluable in 14 subjects with her2-positive (her2 ihc3 or ihc2 and fish ) solid tumors, the objective response rate (orr) was 64.3%, the disease control rate (dcr) was 92.9%. the median progression-free survival (pfs) and intermediate overall survival (os) has not yet been reached. the anti-tumor activity of kn026 and kn046 combination therapy was not affected by prior treatments from trastuzumab and anti-pd-1 immune checkpoint inhibitors and pd-l1 expression.
based on the encouraging efficacy data from the above study, the registration clinical trial（search-01）for the combination therapy of kn026 and kn046 will be initiated. search-01 is planned to be conducted in 20-30 clinical centers in china and 10-20 us clinical centers. the aim of search-01 is to evaluate the efficacy, safety and tolerability of the combination therapy in patients with her2-positive solid tumors including her2-positive gastric cancer/ gastroesophageal junction tumor/ esophageal adenocarcinoma.
the leading pi of the study, professor lin shen from beijing cancer hospital commented “the exploratory study of the combination therapy of kn026 and kn046 is a global late stage clinical study of hre2 positive solid tumors, which reflects the unique charm of multidisciplinary cooperation and breakthroughs in collaboration model. we believed that this new regimen be potentially the transformative therapeutic for her2-positive tumors. search-01 demonstrates the originative research capabilities of chinese pharmaceutical companies, and the innovation in collaboration of the chinese medical community.”
dr. ting xu, founder, chairman and ceo of alphamab oncology, commented, “the results of the phase i study presented at the sitc 2020 showed the excellent efficacy and safety of kn026 kn046 combo against her2-positive solid tumors. we will continue the follow-up studies. we strive to provide solution late line her2-positive breast cancer, gastric cancer and other tumors. meanwhile we are trying to test the combo in early line patients. the combination may offer chemo-free option for patients with her2-positive solid tumors in the first line or even earlier setting.”
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. in pre-clinical studies, kn026 has demonstrated potentially equivalent or superior 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 the world's first recombinant humanized pd-l1/ctla-4 bispecific antibody independently developed by jiangsu alphamab. its innovative designs include: a proprietary ctla-4 domain antibody with a significantly improved safety profile; a bispecific antibody fused with pd-l1 antibody; engineered to target the tumor microenvironment with high pd-l1 expression, and treg clearing function. the preclinical and clinical trial results of kn046 have shown promising efficacy and significantly reduced toxicity to human peripheral system, with the potential to become a breakthrough cancer immunotherapy.
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 a preliminary profile of good safety and promising efficacy. alphamab has received fda clearance to enter phase ⅱ trial of kn046 based on the clinical results in china and australia. the phase ⅲ clinical trials to evaluate efficacy and safety of combination therapy of kn046 and platinum-based chemotherapy in patients with stage iv squamous non-small cell lung cancer have started in china.
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, and japan.
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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