ind approval for combination therapy anti-凯发88

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ind approval for combination therapy anti-her2 bispecific antibody kn026 and ibrance® (palbociclib)

december 28, 2020 08:09 eastern daylight time

suzhou, december 28, 2020 - alphamab oncology (stock code: 9966hk) announced, company has received approval for an ind application recently from national medical products administration (nmpa) of china for combination therapy of kn026 and palbociclib or combination therapy of kn026, palbociclib and fulvestrant for the treatment of her2-positive locally advanced unresectable and/or metastatic breast cancer that has failed the treatment of trastuzumab and taxanes.

breast cancer is the leading malignant tumor that seriously threatens the health of women in the world, and it is also the tumor with the highest incidence in women of china. in 2015, 570,000 women died of breast cancer globally, accounting for about 15% of the total number of tumor deaths in females; the number of new breast cancer cases in china reached 272,000, with more than 70,000 deaths1. the human epidermal growth factor receptor 2 (her2) signaling pathway plays a key role in the growth and development of normal cells, and the abnormal expression of her2 is associated with poor prognosis of breast cancer. according to statistics, 15%-30% of breast cancers will have her2 gene amplification or overexpression. this type of breast cancer has a high degree of malignancy and a poor prognosis, with a median survival time of only 2-3 years; patients with her2-positive tumors progress faster than patients with her2-negative tumors, and their overall survival is significantly shorter before the era of anti-her2 agents2-3. relevant studies have shown that continuous inhibition on the her2 signaling pathway can yield clinical benefit for patients.

at present, the internationally used her2 targeted biologics for the clinical treatment of her2-positive breast cancer include trastuzumab and pertuzumab. however, almost all patients with her2-positive metastatic breast cancer will inevitably develop disease progression. preclinical studies have shown that inhibitors of cyclin-dependent kinase 4 and 6 (cdk4/6) exhibit enhanced her2 activity and increased sensitivity to her2 kinase inhibitors or anti-her2 antibodies4. the combination therapy of standard her2 targeted therapy and cdk4/6 inhibitor can improve the treatment outcome5 of patients with hormone receptor-positive (hr )/her2-positive metastatic breast cancer patients.

kn026 is an anti-her2 bispecific antibody developed by alphamab oncology. kn026 can bind two non-overlapping epitopes of her2 simultaneously, leading to a dual her2 signal blockade. multiple phase i/ii clinical trials show that kn026 has excellent safety and tolerance and it has significant anti-tumor activity in her2-positive breast cancer patients who progressed after multi-line anti-her2 therapy. in march 2020, alphamab oncology and pfizer entered a clinical supply agreement to advance the clinical trial of the combination therapy of kn026 and the oral cdk4/6 inhibitor ibrance® (palbociclib).

this is a multi-center, open-label phase ib/ii clinical study to evaluate the efficacy, safety and tolerability of kn026 in combination with palbociclib in the treatment of locally advanced unresectable or metastatic her2-positive breast cancer patients. professor jiong wu from the cancer hospital of fudan university is the principal investigator. the primary endpoints of the study are dose-limiting toxicity (dlt) and objective response rate (orr). as a potential chemotherapy-free regimen, the trial will bring new hope to patients with her2-positive breast cancer.

in addition, based on large amount of cmc and formulation study, the 325mg dose liquid formulation has been approved for clinical trial. comparing with lyophilized formulation, the adoption of a new formulation simplified the manufacturing process and meanwhile improve the convenience for clinical application.

about kn026

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.

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 bla for kn035(envafolimab) has been accepted by the national medical products administration (nmpa) on december 17.

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.

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alphamab oncology forward-looking statements

this press release contains statements related to our future business and financial performance and future events or developments involving alphamab oncology that may constitute forward-looking statements. these statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. these statements may be identified by words such as "expect," "look forward to," "anticipate" "intend," "plan," "believe," "seek," "estimate," "will," "project" or words of similar meaning. we may also make forward-looking statements in other reports, in presentations, in material delivered to shareholders and in press releases. in addition, our representatives may from time to time make oral forward-looking statements. such statements are based on the current expectations and certain assumptions of alphamab oncology’s management and business operation, many of which are difficult to predict and generally beyond alphamab oncology’s control. these are subject to a number of risks and uncertainties, including but not limited to, uncertainties inherent in research and development, future clinical data and analysis, decisions by regulatory authorities regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, alphamab oncology's ability to benefit from external growth opportunities, trends in exchange rates and prevailing interest rates, the impact of cost containment policies and subsequent changes thereto, the average number of shares outstanding and alphamab oncology’s disclosures. should one or more of these risks or uncertainties materialize, or should underlying expectations not occur or assumptions prove incorrect, actual results, performance or achievements of alphamab oncology may (negatively or positively) vary materially from those described explicitly or implicitly in the relevant forward-looking statement. other than as required by applicable law, alphamab oncology undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.


[1] chen, w., et al., cancer statistics in china, 2015. ca cancer j clin, 2016. 66(2): p. 115-32.

[2] iqbal, n. and n. iqbal, human epidermal growth factor receptor 2 (her2) in cancers: overexpression and therapeutic implications. mol biol int, 2014. 2014: p. 852748.

[3] qiu, m.z., et al., her2-positive patients receiving trastuzumab treatment have a comparable prognosis with her2-negative advanced gastric cancer patients: a prospective cohort observation. int j cancer, 2014. 134(10): p. 2468-77.

[4] kai zhang, ruoxi hong, lee kaping, et al. cdk4/6 inhibitor palbociclib enhances the effect of pyrotinib in her2-positive breast cancer. cancer lett. 2019 apr 10; 447:130-140.

[5] sara m tolaney , andrew m wardley, stefania zambelli, et al. abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with hormone receptor-positive, her2-positive advanced breast cancer (monarcher): a randomised, open-label, phase 2 trial.lancet oncol .2020 jun;21(6):763-775.