內容目錄
In February 2022, “Clinical Cancer Research”, a well-known international journal in the field of oncology, published the results of a phase I clinical study of the HER2 bispecific antibody KN026 in the treatment of HER2-positive metastatic breast cancer.
Breast cancer is one of the most common cancers in women worldwide, and approximately 15%~20% of cases are characterized by overexpression or amplification of HER2/ERBB2, which can be transmitted by HER2 Effective treatment with targeted drugs. In recent years, trastuzumab, pertuzumab, antibody-drug conjugates (ADCs, such as T-DM1 and DS8201), and TKI inhibitors (such as lapatinib, neratinib, pyrotinib, and Tucatinib) has been shown to significantly improve outcomes in patients with HER2-positive breast cancer. However, the development of next-generation anti-HER2 drugs to improve therapeutic efficacy and reversal of drug resistance is still an urgent medical need that remains unmet.
KN026 is a novel anti-HER2 bispecific antibody that simultaneously binds two non-overlapping epitopes of HER2, resulting in a blockade of HER2 signaling, superior to trastuzumab Antibody or Pertuzumab alone can achieve the effect of combined use of Trastuzumab and Pertuzumab.
Preclinical data demonstrate that KN026 retains antibody-dependent cell-mediated cytotoxicity compared to trastuzumab combined with pertuzumab against HER2-overexpressing cancer cells in vitro and in vivo were similar or stronger, and could kill tumor cells that had become resistant to the combination of trastuzumab and pertuzumab.
Codename:KN026
Target:HER2
First Approval in the U.S.: Not yet approved
First approved in China: Not yet approved
clinical data
in this first-in-human In studies (KN026-CHN-001; NCT03619681), we aimed to evaluate the safety, tolerability, pharmacokinetics, preliminary efficacy and potential predictive biomarker activity of KN026 as monotherapy in patients with HER2-positive breast cancer .
A total of 63 female patients were included between September 2018 and December 2019. The median age of enrolled patients was 54 years; 36 (57.1%) patients received more than 3 prior antitumor regimens, of whom 61 (96.8%) received trastuzumab and 32 (50.8%) Patients received anti-HER2-TKI therapy, and 15 (23.8%) patients received anti-HER2-ADC therapy; 60 (95.2%) patients had visceral disease at baseline, and the common metastatic sites were lung (55.6%) and liver (28.6%) .
In this trial, all patients were assessed for response. At a median follow-up of 15 months, of 63 patients with measurable baseline lesions and at least one post-baseline scan, tumor shrinkage was observed in 46 (73.0%) patients strong>. Fifteen (23.8%) patients achieved the best partial response (PR), 1 (1.6%) patient achieved a confirmed complete response (CR), and 28 patients (44.4%) patients had stable disease (SD), and 18 (28.6%) patients had progressive disease (PD). The confirmed objective response rate (ORR) was 25.4%, and the disease control rate (DCR) was 69.8%.
Legend: Tumor response in all evaluable patients in this study. A, Patients with at least one post-treatment imaging assessment had a maximum (%) reduction in tumor size from baseline according to RECIST v1.1. The length of the bar graph represents the maximal decrease or minimal increase (s) of target lesions. B, Individual percent change in tumor burden over time as assessed according to RECIST v1.1.
Median progression-free survival (PFS) was 5.6 months, and the 6-month PFS rate was 47.7%; median overall survival (OS) was not reached, and the 12-month OS rate was 85.8%.
In addition, 2 patients previously treated with Pertuzumab received KN026 at the recommended phase II dose (RP2D) and achieved PR thereafter. For example, one of the responders had previously received adjuvant chemotherapy and radiation (DFI = 20 months); first-line docetaxel/trastuzumab/pertuzumab (median PFS was 10 months); second-line card Pecitabine/lapatinib, median PFS was 7 months; third-line treatment with KN026 (30 mg/kg every 3 weeks), median PFS was 6.77 months.
Adverse Reactions
All enrolled patients were evaluated for safety. The median duration of treatment was 5.6 months, and no dose-limiting toxicities (DLTs) were observed at all dose levels.
Adverse reactions of any grade related to treatment were observed in 56 patients (88.9%). The most common (≥10%) adverse reactions included: pyrexia (23.8%), diarrhea (22.2%), aspartate aminotransferase increasehigh (22.2%), alanine aminotransferase increased (22.2%), leukopenia (17.5%), hypokalemia (12.7%), infusion-related reactions (12.7%), neutropenia (12.7%), and rash (11.1%).
Grade 3 adverse reactions were reported in 4 patients, mainly including: infusion-related reactions, elevated transaminases, ventricular arrhythmias and cardiac myxoma. No grade 4 or 5 adverse reactions were reported.
Conclusion
This is the world’s first proof-of-concept clinical trial targeting HER2 dual antibody in metastatic breast cancer. Taken together, KN026 is well tolerated and manageable with a manageable safety profile, and exhibits positive antitumor activity in HER2-positive breast cancer patients.
[Important Notice]All article information is for reference only, specific treatment Follow the doctor’s advice!
Diabetes reversal is not a dream! Endocrinologists launch 2 Type Diabetes Intensive Reverse Glucose Management Alliance
Text/Yangcheng Evening News All-Media Reporter Zhang Hua Correspondent Wu Zhenpeng Zhang Cancheng Photo/Hospital Provided Ms. Chen, 43, is from Dali, Yunnan, and has been working in Dongguan, Guangdong. Recently, Ms. Chen accidentally touched a small fleshy growth on her anus while taking a bath. “Although I have hemorrhoids for five or six years, I still feel uncomfortable when I go to the toilet…
73% of patients’ tumors shrink! New HER2 drug KN026 It is expected to solve the problem of breast cancer drug resistance!
Text/Wang Shuhui, correspondent of Zhang Hua, an all-media reporter of Yangcheng Evening News, “During the Spring Festival, 4 cases of aortic dissection were received in February.” Zhong Zhimin, Director of Provincial Cardiovascular Surgery, Guangdong Second People’s Hospital Said, “This situation is a bit unexpected, and it may be related to the extremely cold weather during the Spring Festival this year. Fortunately, the timely operation, all…
Different goddess festival, walk into the “healing she∙narrative space” in the cancer hospital
Text/Yangcheng Evening News All-Media Reporter Chen Hui Correspondent Chen Jun “Hemerocallis blooms on the high green hills, pick one for my little girl, and pin it on the tip of your hair, Hold it in my heart…” In a warm melody of “Hemerocallis Flower”, patients and their families are arranging flowers, listening to the doctor’s small psychological relief class, and…
A small fat growth in the anus is not a hemorrhoid It’s a rectal tumor!
In February 2022, the journal Lung Cancer Translational Research published a study evaluating the combination of the PD-1 inhibitor nivolumab and recombinant human endostatin in previously treated patients with advanced non-small cell lung cancer. A study report on safety and efficacy in cell lung cancer (NSCLC). Immune checkpoint inhibitors (IC…
Long time to see! II Ten years of rotten face can not be cured? It turns out that the root of the disease is in his own heart!
Text/Yangcheng Evening News All Media Reporter Chen Hui Intern Zheng Minshan Tu/Visual China’s slightly obese people want to try traditional Chinese medicine to lose weight, but they are afraid that it is too hard to drink soup and medicine, and they don’t have time to go to the hospital often for acupuncture to lose weight? Wang Shuxin, director of the Rehabilitation Center of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, recommends two methods of losing weight in traditional Chinese medicine, which are suitable for no time…
Tear-like pain in the chest and back? Beware of this dangerous disease!
This is often seen in outpatient clinics. Some people’s blood vessels age faster than they age. This is “premature vascular aging.” People’s health and longevity are closely related to the health of the body’s blood vessels. Therefore, there has always been a saying that “vascular aging causes all kinds of diseases”. Many situations in life will accelerate the aging of blood vessels. Blood vessels…
National Ear Day Science: A few truths you must know about the ear
Click to load the picture The medical staff is checking the children’s ears Photo by Han Suyuan China News Service, Hefei, March 2 (Fei Qinru Han Suyuan) March 3 is the 23rd National “Ear Love Day”. “The ear has two important functions, one is hearing, which is called deafness or hearing loss; the other is balance sense, balance…
Immune combined with anti-angiogenic drugs “combination punch” “Or break the drug resistance dilemma of lung cancer
Many people have probably heard that blood pressure lowering drugs cannot be taken with grapefruit. Many hypertensive patients are taboo for grapefruit. In fact, for hypertensive patients, it is not All people can’t eat grapefruit, because grapefruit contains furanocoumarin, which can inhibit…
National Committee of the Chinese People’s Political Consultative Conference Li Guodong: Strengthening primary medical and health services can relieve hospital pressure
Everything is growing and the sun is shining, but you feel so tired? Seasonal depression is high, and experts teach you how to stay away from our reporter He Lina, trainee reporter Xu Ziying, correspondent Zhou Runtao, Wang Wenting, and Li Bin. On March 1, Hangzhou officially announced the arrival of spring. However, in this season of growth, in the psychiatric departments of many hospitals in Hangzhou, due to depression,…
Want to lose weight but afraid of “hardship”? Chinese medicine therapy can help
China News Service, Shanghai, March 8 (Reporter Chen Jing) Among the many malignant tumors that seriously threaten women’s life and health, ovarian cancer is known as “the king of women’s cancer”. The reporter learned on the 8th that both patients with newly diagnosed ovarian cancer and patients with platinum-sensitive recurrence can benefit from targeted drugs-PARP inhibitors, which greatly…
40-year-old 60-year-old blood vessels? Doctor reminds: blood vessels should also prevent premature aging
Recently, the domestic new crown epidemic has shown the characteristics of many points, wide areas, and frequent occurrences. In view of the stronger transmission power, faster transmission speed and more concealed transmission process of the Omicron variant strain, the general public is requested to consciously abide by the epidemic prevention regulations in units, communities, public transportation, and public places. At the same time, do personal protection and wear your mouth properly…
You are more afraid of the cold weather than others? Cook this bowl of porridge after get off work
Text/Yangcheng Evening News All-Media Reporter Chen Hui Correspondent Liu Qingjun Tu/Visual China has been cold for several days, and the friends are all wrapped up in zongzi. Will you find that even if you wear a lot of clothes, your hands and feet are always cold, as if you are more afraid of cold than others. Professor Lan Senlin from the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine recommended a…
@all women, health concerns at every stage Anything?
Text/Photo by Yangcheng Evening News All-Media Reporter Zhang Hua Patients with early-stage lung cancer were treated with immunotherapy to remove all tumor cells. Do these patients still need surgery? This is an exciting and hesitant multiple-choice question for thoracic surgeons. On February 26, at the 10th Guangzhou Lung Cancer Forum, the Lung Cancer Research Institute of Sun Yat-Sen University…
What are high blood pressure medicines? What are the principles of the six common antihypertensive drugs? You can’t eat grapefruit when you take the medicine?
The central nervous system (CNS) is one of the common sites of metastasis in patients with non-small cell lung cancer (NSCLC). Brain metastases or meningeal metastases occur in 23% to 36% of patients with NSCLC during disease progression. With the development of individualized therapy and the target of tyrosine kinase inhibitors (TKIs)…
Do you know how much hair a person loses in a month? Quick collection of hair care cheats
Recent science news mentions the results of a study that says that more chewing increases the thermic effect of food, which is equivalent to reducing food calories. So, does chewing slowly really help you lose weight? Regarding the problem of “chewing and swallowing slowly will raise blood sugar” that diabetic patients are concerned about, whether…
Women’s day on March 8, all-round maintenance for women Cheats
“March 8 Women’s Day” is coming, I wish all goddesses health and beauty! On this occasion, Health Times presents a comprehensive maintenance recipe for female friends! 1. Enriching blood, beautifying face, freezing age, and having sufficient qi and blood are the pursuits of many women. Which foods can nourish blood? Many experts recommend trying these! 1….
Wuhan CDC Reminder: Do Good personal protection, deal with Omicron
China News, Harbin, March 8 (Reporter Liu Xiju) On the 8th, the Harbin Center for Disease Control and Prevention released a message: From 0:00 to 15:00 on March 8, 2022, the Sixth Hospital of Harbin 1 new confirmed case of new coronary pneumonia was reported. He is currently being treated in isolation at the designated hospital. According to the flow adjustment results, now…
High blood pressure in winter is normal? What are the common causes of high blood pressure in the morning? What are the hazards?
Ms. Liu has been suffering from high blood pressure for many years. She usually takes medicine and measures blood pressure on time. When she woke up a few days ago, she suddenly felt dizzy. When she went to the hospital, the doctor told her that it was a symptom of a sudden increase in blood pressure in the morning. Although her blood pressure was usually well controlled, she still had to pay attention to blood pressure fluctuations at specific times. Ms. Liu asked…
The CU5 Cancer Center Medical Team Help post-95 anti-cancer girls return to school
Text and photos/Jiang Xin, correspondent of Zheng Da, an all-media reporter of the Yangcheng Evening News, “I didn’t expect my grades to be so good, and I felt that all the hard work was worth it.” At the moment when he saw the results of the preliminary examination for the postgraduate entrance examination, he was 24 years old. Chen Linqiong cried with joy. In the past two years, she has experienced cancer, unemployment, breakup… Her experiences are cited online…
Double-dose osimertinib in EGFR-mutant lung cancer Meningeal metastasis is effective
(Fighting against New Coronary Pneumonia) Shanghai added 18 new cases of new corona virus infection and a medium-risk area China News Agency, Shanghai, March 8 (Reporter Chen Jing) Shanghai New Coronary Pneumonia held on the 8th At the press conference on epidemic prevention and control, Wu Jinglei, director of the Shanghai Municipal Health Commission, introduced that Shanghai reported 3 new confirmed cases of new coronary pneumonia…