● as of august 10, 2021, 24 patients with her2-positive other solid tumors (non-breast cancer/gastric cancer ) who received ≥1l prior systemic therapy were enrolled, 20 patients were evaluable for overall response：the orr was 55.0%, the dcr was 85.0%, the 6-month pfs rate was 84.1%; out of 11 evaluable crc patients, the orr and dcr was 45.5% and 90.9% respectively.
suzhou, china, april 11, 2022 - 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 an e-poster at the aacr annual meeting 2022 (aacr 2022).
kn026-203 is an open-label, phase ii, multi-center clinical study to evaluate the efficacy and safety of kn026 in combination with kn046 in the treatment of her2-positive solid tumors. enrollment of all 102 patients, including her2-positive gc/gej, breast cancer as well as other her2-positive solid tumors, has been completed. the preliminary efficacy data for kn026 in combination with kn046 in her2-positive breast cancer from this study were positive and were presented at the 2021 sabcs. here we reported the preliminary efficacy and safety results of kn026 in combination with kn046 in patients with locally advanced unresectable or metastatic her2-positive other solid tumors (non-breast cancer/gastric cancer).
as of august 10, 2021, 24 patients with locally advanced unresectable or metastatic her2-positive other solid tumors who progressed after ≥1l prior systemic therapy were enrolled, including 14 crc patients, 4 nsclc patients, 4 gallbladder cancer patients, 1 renal pelvis cancer patient, and 1 pancreatic cancer patient. patients received kn046 (iv.5mg/kg q3w) plus kn026 (iv.30mg/kg q3w, loading on c1d1, d8) until progression, unacceptable toxicity or patient withdrawal. the primary endpoint was orr as assessed by the investigator q6w according to recist 1.1.
20 and 24 patients were evaluable for overall response and safety, respectively. the orr was 55.0% (11/20, 95% ci: 31.5-76.9), the dcr was 85.0% (17/20, 95% ci: 62.1-96.8), and the 6-month pfs rate was 84.1%. out of 11 evaluable crc patients, the orr and dcr was 45.5% (5/11, 95% ci: 16.7-76.6) and 90.9% (10/11, 95% ci: 58.7-98.8) respectively.
in terms of safety, 20 of 24 patients (83.3%) had experienced treatment-related adverse event (traes) of any grade, and total 4 of 24 patients (16.7%) had experienced ≥grade 3 traes. the most common (≥10%) traes were infusion-related reactions (29.2%), diarrhea (19.4%), alanine aminotransferase increased (16.7%), and aspartate aminotransferase increased (16.7%), vomiting (12.5%), and decreased appetite (12.5%). no treatment-related deaths were observed.
professor shen lin from peking university cancer hospital, the principal investigator, commented: “in addition to breast and gastric cancer, her2 gene amplification or overexpression also occurs in other solid tumors, including but not limited to crc, nsclc, gallbladder cancer, renal pelvis cancer, and pancreatic cancer. currently, there are few reports on immunotherapy combined with her2-targeted therapy in those patients. we are pleased to see that combining kn026 with kn046, as a chemotherapy-free regimen, has shown good efficacy, with an orr of 55%. especially in colorectal cancer, which is highly prevalent in china, the orr is also as high as 45.5%. we look forward to further exploring the great value of this chemotherapy-free regimen in follow-up clinical studies, bringing hope to patients in need.”
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 in combination, and was superior to either single agent, 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 good 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 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 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, 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.
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. five 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.
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