Multiple clinical research data of dual antibodies KN046 and KN026 will be unveiled in ASCO 2021, covering multiple tumor types such as lung cancer and pancreatic cancer

*Only for medical professionals to read and reference.
Recently, 3 clinical research data of KN046 (PD-L1/CTLA-4 bispecific antibody) will be presented in the ASCO 2021 annual meeting in the form of posters, including: KN046 combined with platinum-based chemotherapy for the treatment of advanced non-small cells Phase II clinical study data of patients with lung cancer (study number: KN046-202); Phase II clinical study data of KN046 combined with albumin paclitaxel/gemcitabine in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC) (study number: KN046-IST-04); Phase II clinical study data of KN046 combined with paclitaxel/cisplatin in the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) (study number: KN046-204)
.

The preliminary efficacy data of the anti-HER2 bispecific antibody KN026 in patients with advanced HER2-positive gastric and gastroesophageal junction cancer are announced in abstract form
.

The poster was published online on ASCO 2021 on June 4, US Eastern Time.
The electronic poster can be viewed on the company's website
.

Subject: KN046 combined with platinum-based chemotherapy in the treatment of patients with advanced non-small cell lung cancer: Phase II, open, multi-center study Abstract number: 9060 First author: Professor Yang Yunpeng, Sun Yat-sen University Cancer Center KN046- 202 (NCT04054531) is a phase II, open, multi-center clinical study aimed at evaluating the efficacy, safety and tolerability of KN046 combined with platinum-based chemotherapy in patients with advanced non-small cell lung cancer.
The results show that KN046 is well tolerated It is effective for the first-line treatment of advanced non-small cell lung cancer; the benefits of progression-free survival (PFS) and overall survival (OS) are observed in patients with PD-L1≥1% and PD-L1<1% To a similar survival curve, especially for patients with squamous cell carcinoma with PD-L1≥1%, the benefit is obvious
.

 As of January 19, 2021, a total of 87 patients with advanced non-small cell lung cancer who have not received systemic treatment were enrolled, including 51 patients with non-squamous cell carcinoma and 36 patients with squamous cell carcinoma
.

46 patients had PD-L1≥1%, and 37 patients had PD-L1<1%
.

The median treatment time was 21 weeks
.

 Among 81 patients with evaluable efficacy, the objective response rate (ORR) was 50.
6% (95% CI 39.
3%-61.
9%), and the disease control rate (DCR) reached 87.
7% (95% CI 78.
5%-93.
9%)
.

In patients with non-squamous non-small cell lung cancer, ORR and DCR were 45.
8% (95% CI 31.
4%-60.
8%) and 89.
6% (95% CI 77.
3%-96.
5%), respectively; in patients with squamous non-small cell lung cancer Among them, ORR and DCR were 57.
6% (95%CI 39.
2%-74.
5%) and 84.
8% (95%CI 68.
1%-94.
9), respectively
.

 The median progression-free survival (mPFS) is 5.
9 months (95%CI 5.
3-8.
7), and the median overall survival (mOS) has not yet been reached; the 12-month and 15-month survival rates (OS rates) are both 74.
9 %; PD-L1 ≥1% and PD-L1<1% patients have similar initial OS, PD-L1 ≥1% patients, mPFS is 6.
7 months, and PD-L1 ≥1% squamous cell carcinoma patients have mPFS 10.
8 months
.

 In terms of safety, 22 patients (25.
3%) experienced treatment-related adverse events (TRAE) of grade 3 or above, mainly diarrhea (5.
7%), elevated alanine transaminase (4.
6%), and infusion reactions (3.
4 %), skin rash (3.
4%), elevated aspartate aminotransferase, allergic dermatitis, and immune-related pneumonia (both 2.
3%)
.

Adverse events are controllable
.

 The principal investigator of the clinical trial and Professor Zhang Li from Sun Yat-sen University Cancer Hospital said: "Lung cancer is the malignant tumor with the highest incidence and mortality in China.
In recent years, immunotherapy has significantly improved the long-term survival of patients with advanced non-small cell lung cancer.
However, the overall prognosis and long-term efficacy of patients still need to be improved urgently
.

We are very pleased to see that Corning Jereh’s bispecific antibody KN046 exhibits advantages such as ORR, PFS and OS in lung cancer patients, which means that patients with advanced NSCLC may gain A better treatment plan
.

We look forward to verifying its great value as a first-line treatment in follow-up studies
.

"Subject: KN046 combined with albumin paclitaxel/gemcitabine as the first-line treatment for unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) Effectiveness and Safety Abstract Number: 4138 First Author: Professor Jin Gang, First Affiliated Hospital of Naval Military Medical University (Shanghai Changhai Hospital) Pancreatic cancer is recognized by the medical community as the "king of cancer", of which about 90% of pancreas The cancer is pancreatic ductal adenocarcinoma (PDAC), which is difficult to detect, progresses quickly, and has a high fatality rate.
The patients have no obvious symptoms in the early stage.
Once they are found that most of them have lost the indications for surgery, there is a lack of effective clinical treatment methods, and there are huge unsatisfied Clinical needs
.

 The investigator initiated the Phase II clinical study in China, enrolling patients with unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) confirmed by histology or cytology, with an ECOG PS of 0-1.
Received systemic treatment for unresectable locally advanced or metastatic disease
.

Patients received KN046 combined with albumin paclitaxel and gemcitabine for 4-6 cycles, and then received KN046 (5mpk, Q2W) maintenance treatment
.

Tumor evaluation was performed according to RECIST 1.
1 every 8 weeks
.

The primary study endpoint is the ORR assessed by the investigator, and the secondary study endpoints are DCR, duration of efficacy (DOR), time to disease progression (TTP), PFS, OS, and safety
.

 As of January 15, 2021, a total of 17 patients were enrolled, the median age (range) was 56 (36-75) years, 9 patients had an ECOG PS score of 1, and 7 patients had liver metastases at baseline
.

The median exposure time of KN046 was 9.
5 weeks
.

Among them, 9 patients received at least one tumor assessment and entered the efficacy analysis data set, and 17 patients entered the safety analysis data set
.

Partial response (PR) was 55.
6% (5/9), stable disease (SD) was 33.
3% (3/9); ORR was 55.
6% (95%CI 21.
2-86.
3), DCR was 88.
9% (95%CI 51.
8) -99.
7)
.

The incidence of treatment-related adverse events (TRAE) was 64.
7%, and grade 3 and above accounted for 29.
4%
.

The most common (≥10%) TRAEs were: elevated alanine aminotransferase (n=5, 29.
4%), nausea (n=3, 17.
6%), skin rash (n=3, 17.
6%), and aspartame Elevated acid transaminase (n=2, 11.
8%), diarrhea (n=2, 11.
8%), hyperphosphatemia (n=2, 11.
8%), fever (n=2, 11.
8%), vomiting (n= 2, 11.
8%)
.

 The main investigator of the clinical trial, Professor Jin Gang from the First Affiliated Hospital of Naval Military Medical University, said: “Pancreatic cancer is one of the common malignant tumors of the digestive system in China, with a high degree of malignancy and a very poor prognosis
.
From
2015 to 2020, China New cases of pancreatic cancer increased by about 31.
6%, and death cases increased by about 43.
5%.
New cases and deaths of patients were almost the same, and an effective treatment plan was urgently needed
.

At present, domestic and foreign guidelines recommend albumin paclitaxel combined with gemcitabine (AG plan) as The first-line treatment of advanced PDAC, but the curative effect is limited and chemotherapy resistance is unavoidable
.

The synergy of immune checkpoint inhibitors combined with chemotherapy may be a new direction for the treatment of pancreatic cancer
.

We are very pleased to see that the PD-L1/CTLA-4 dual-antibody KN046 combined with AG regimen achieved an objective response rate of 55.
6% in patients with advanced pancreatic ductal adenocarcinoma, which is more than double the historical ORR of the AG regimen
.

We look forward to continuing to explore its great value in follow-up clinical studies, and bring new hope for the treatment of patients with advanced pancreatic cancer
.

Subject: Efficacy and safety of KN046 combined with paclitaxel/cisplatin in the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) Abstract number: 4062 First author: Professor Xu Jianming, General Hospital of the Chinese People's Liberation Army KN046-204 Including 3 cohorts, one of which enrolled patients with unresectable locally advanced, recurrent or metastatic ESCC (ECOG PS 0-1 points) who had not received systemic treatment in the past and were confirmed by histology or cytology (ECOG PS 0-1 points)
.

KN046 combination Paclitaxel and cisplatin are treated for 4 to 6 cycles, and then the patient receives KN046 (5mpk, iv, Q2W) maintenance treatment
.

Tumor evaluation is performed according to RECIST 1.
1 every 6 weeks
.
The
primary study endpoint is the ORR evaluated by the investigator
.
The
secondary study endpoints include DCR, safety, pharmacokinetics (PK) and immunogenicity
.

 As of January 14, 2021, 15 patients were enrolled in this cohort, all male, 52.
3% ≥ 60 years old, 64% ECOG PS 1 point , 80% of patients had distant metastases at baseline
.

The median exposure time of KN046 was 11.
4 weeks, and the average treatment period of KN046 was 2.
4 cycles
.

Twelve subjects entered the efficacy analysis data set, the ORR was 58.
3%, and the DCR was 91.
6%
.

Seven patients (58.
3%) achieved PR, and one subject achieved complete remission of the target lesion
.

Four patients (33.
3%) achieved SD, of which the target lesions in 3 subjects had a maximum reduction of more than 20%
.

Fifteen subjects entered the safety analysis data set.
The incidence of treatment-related adverse events (TRAE) was 80.
0%, and grade 3 and above accounted for 13.
3%
.

The incidence of infusion reactions was 7.
8%, mostly grade 1-2
.

The incidence of immunotherapy-related adverse reactions (irAE) was 53.
3%, and the most common irAE ≥ Grade 3 were nausea (n=1, 6.
7%) and skin rash (n=1, 6.
7%)
.

 The main investigator of the clinical trial, Professor Xu Jianming from the Chinese People’s Liberation Army General Hospital, said: “Esophageal cancer is a malignant tumor that originates from the epithelium of the esophageal mucosa.
The pathological types include squamous cell carcinoma and adenocarcinoma.
It is the most common malignant tumor in China.
One, about 90% of the pathological type of esophageal cancer is squamous cell carcinoma
.

In recent years, immunotherapy has become the standard for second-line treatment of esophageal cancer, but the prognosis of advanced esophageal squamous cell carcinoma is still poor clinically
.

In KN046-204 In the study, KN046 has achieved positive efficacy and safety data in the first-line treatment of patients with advanced esophageal squamous cell carcinoma, which indicates that this bispecific antibody is expected to become a better treatment option
.

Subject: The preliminary efficacy of HER2 bispecific antibody KN026 in patients with advanced HER2-positive gastric and gastroesophageal junction cancer.
Abstract Publication number: e16005 First author: Professor Xu Jianming, Chinese People's Liberation Army General Hospital KN026-202 is a single-arm , An open, multi-center phase II clinical study, including advanced gastric and gastric junction adenocarcinomas that have received at least first-line treatment in the past.
According to the test results of the central laboratory, they are divided into two types: high expression of HER2 (HER2 positive) and low expression of HER2 A cohort designed to evaluate the efficacy of KN026 in these two cohorts
.
The
 results show that KN026 has a good efficacy in HER2-positive patients, regardless of whether the patients have received trastuzumab in the past
.

As of the data deadline, cohort 1 was enrolled in group 20 For a patient with high HER2 expression, the median treatment time was about 20 weeks, the ORR was 55.
6%, the DCR was 72.
2%, the 9-month progression-free survival rate (PFSR9m) was 60.
4% (95% CI 24.
4%-83.
5%), DOR , MPFS and mOS have not yet been reached
.

For the 9 patients who have previously received trastuzumab treatment, ORR was 44.
4%, DCR was 66.
7%, mPFS was 5.
6 months, and mOS was 11 months
.

 Xu Xu, Chairman and President of Corning Jerry Dr.
Ting said: "We are very pleased to see the results of multiple studies of KN046 and KN026 released in ASCO 2021
.

Based on these results, we have started clinical registration of KN046 in first-line squamous non-small cell lung cancer and posterior-line thymic cancer
.

In addition, the first-line of pancreatic cancer and liver cancer, and the phase III clinical trials of PD-1 resistant non-small cell lung cancer are also being launched
.

Regarding KN026, its excellent efficacy and safety make it very promising in early-line, adjuvant and neoadjuvant Her2-positive solid tumors
.

In addition, we are also actively exploring the potential of the combination of the two as chemotherapy-free tumor treatment options
.

It is hoped that through these studies, we can create a post-PD-1 era and bring effective therapeutic drugs to more patients
.

I would also like to express my heartfelt thanks to the experts who led and participated in these clinical trials and the many patients who participated in the trials
.

▎About KN046KN046 is a PD-L1/CTLA-4 bispecific antibody independently developed by Corning Jereh.
Its innovative design includes the fusion of CTLA-4 and PD-L1 single domain antibodies with different mechanisms; it can be targeted for enrichment.
In the tumor microenvironment with high expression of PD-L1 and the elimination of Tregs that inhibit tumor immunity
.

 KN046 has been launched in Australia and China to cover more than 10 types of tumors such as non-small cell lung cancer, triple negative breast cancer, esophageal squamous cell carcinoma, liver cancer, and pancreatic cancer.
Nearly 20 clinical trials in different phases, and the results of the trials have shown that patients have survival benefits
.

Based on the clinical trial results obtained in Australia and China, the US FDA approved KN046 to directly enter the phase II clinical trial in the United States, and awarded KN046 in September 2020 Qualified as an orphan drug for the treatment of thymic epithelial tumors
.

Four key registered clinical trials  of KN046 are currently in progress
.

▎About KN026KN026 is an anti-HER2 double developed by Corning Jereh using the Fc heterodimer platform technology (CRIB) with independent intellectual property rights Specific antibodies can bind to two non-overlapping epitopes of HER2 at the same time, leading to double HER2 signal blockade, achieving the effect of trastuzumab and pertuzumab used alone or in combination, such as exhibiting higher affinity , And has excellent tumor suppression effect in HER2-positive tumor cell lines
.

At the same time, KN026 also has an inhibitory effect on HER2 low-expressing tumors and trastuzumab-resistant cell lines
.

 KN026 has been approved by the National Medical Products Administration (NMPA) and the U.
S.
Food and Drug Administration (FDA) in 2018.
A number of Phase I/II clinical trials are currently underway in China, and phase I clinical trials are being promoted in the United States.

.

The results of phase I clinical trials showed that KN026 has good tolerability and safety, and showed significant anti-tumor activity in patients with HER2-positive breast cancer who have progressed after multi-line anti-HER2 treatment
.

 ▎About Corning Jereh Corning Jereh Biopharmaceuticals focuses on the research and development, production and commercialization of innovative anti-tumor drugs
.

On December 12, 2019, the company was listed on the main board of the Hong Kong Stock Exchange
.

 Corning Jereh Biopharmaceuticals has a discovery, R&D, and manufacturing platform for the entire industry chain in bispecific antibody and protein engineering
.

The company's product pipeline includes 15 highly differentiated anti-tumor drug candidates with independent intellectual property rights, mainly double antibodies, and a Covid-19 multifunctional antibody, four of which are in China, the United States, Japan, and Australia It is in clinical phase I-III
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The marketing application of Envolimab Injection (KN035) has been formally accepted by the National Medical Products Administration (NMPA) and included in the priority review
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 The company has a number of technical platforms with independent intellectual property rights such as heterodimers and hybrid antibodies, and large-scale production capabilities that meet the cGMP standards of China, the United States and the European Union, and have passed a complete quality system including multiple audits of the European Union QP.

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The company is committed to building an internationally leading, multi-dimensional drug development and industrialization platform, focusing on multifunctional biomacromolecule new drugs, benefiting patients in China and around the world
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 *This article is only used to provide scientific information to medical professionals, and does not represent the views of this platform