A number of studies will be unveiled in 2021ASCO Rongchang Biowidicitumumab will be approved soon

Recently, a class of drugs Rongchang biological "injection latitude Brindisi trastuzumab " listing application (related to admissibility is CXSS2000044) was changed to "the approval" in a state of NMPA, is expected to soon be officially approved, it become Thailand The second new drug approved by Rongchang Biological after Xipu
.

Vidicuzumab (R&D code: RC48, trade name: Aidixi) is an antibody conjugate (ADC) drug independently developed by Rongchang Biologics, which is loaded with a humanized HER2 antibody and toxin-methyl auristatin E(MMAE) is formed by coupling with each other through a linker that can be cleaved by cathepsin, and has an optimized drug-antibody ratio
.

In August 2020, the listing application for HER2 overexpression of locally advanced or metastatic gastric cancer (including gastroesophageal junction cancer) that has received at least 2 systems of chemotherapy after the treatment of recurrence/metastasis by Vidicizumab was accepted by CDE and became a domestic The first domestic ADC drug reported for production

The marketing application of Vidicuzumab for the treatment of gastric cancer is based on its single-arm, open, multi-center pivotal II clinical trial data in patients with HER2-positive locally advanced or metastatic gastric cancer
.

The study enrolled 127 patients with HER2 overexpression (including ICH3+, IHC2+/FISH+, and IHC2+/FISH- patients) who had previously received 2-line or above-line system chemotherapy for advanced gastric cancer (including gastroesophageal junction adenocarcinoma)

The results of the study announced at the ASCO2020 meeting showed that the main efficacy indicator objective response rate (ORR) evaluated by the Independent Efficacy Evaluation Committee (IRC) was 24.
4%, the median progression-free survival (PFS) was 4.
1 months, and the median total The survival time (OS) is 7.
5 months
.

In terms of safety, common adverse events of RC48 include decreased white blood cell counts, hair loss, and decreased neutrophil counts, mainly mild to moderate, and clinically controllable

China has the highest incidence of gastric cancer in the world, accounting for about 50% of the global number of patients.
However, there is a lack of effective treatment methods for advanced gastric cancer in the world
.

The above research data show that vedicitumumab is positive for HER2, including HER2 low expression (IHC 2+/FISH-) locally advanced or metastatic gastric cancer (including gastroesophageal junction adenocarcinoma) has outstanding efficacy and is expected to fill up HER2 overexpression Locally advanced or metastatic gastric cancer (including gastroesophageal junction adenocarcinoma) has huge and urgent medical needs for third-line and post-third-line treatment

In addition to the treatment of gastric cancer, Vidicuzumab has also been developed to treat HER2-expressing urothelial cancer, breast cancer, biliary tract cancer and non-small cell lung cancer
.

Among them, the indication of vedicitumumab for urothelial carcinoma (UC) has been granted breakthrough therapy designation by the FDA and CDE successively.

It is worth mentioning that at the 2021ASCO conference that is being held recently, the latest data of a number of clinical studies of Vidicuzumab (RC48) was presented in the form of poster discussions and posters
.

► RC48 is used in a single-arm, multi-center phase II clinical study of HER2 overexpression locally advanced or metastatic urothelial carcinoma
.

[Wallpaper display]

The study was carried out in patients with locally advanced or metastatic HER2 overexpression after failure of previous multi-line chemotherapy.
A total of 64 patients were enrolled from December 2018 to September 2020, of which patients who had previously received second-line and above therapy were 85.
9%

As of March 2021, the objective effective rate of independent imaging assessment has reached 50%, the median progression-free survival time is 5.
1 months, and the median survival time is 14.
2 months
.

The most frequently reported TRAEs are increased AST (46.

► A phase Ib/II study of RC48 combined with teriprizumab in the treatment of locally advanced or metastatic UC
.

[Wallpaper display]

The study is a dose escalation and expansion clinical study of teriprizumab combined with RC48 for at least first-line treatment failure or intolerance/unwillingness to receive cisplatin chemotherapy for metastatic urothelial cancer.
The main research endpoint is the combination The safety of treatment
.

As of April 28, 2021, a total of 19 patients have completed at least one treatment administration, and 17 patients have completed at least one efficacy evaluation

       The results showed that the ORR reached 94.
1% (16/17), of which 3 cases achieved complete remission and 13 cases achieved partial remission.
Among the 19 patients who received the study treatment, the most commonly reported TRAEs were anorexia (79.
0%) and fatigue (68.
4%), elevated ALT/AST (57.
9%) and peripheral sensory neuropathy (57.
9%)
.

       ► A meta-analysis of Phase I and Phase 1b studies of RC48 in the treatment of HER2-positive and HER2 low-expressing advanced or metastatic breast cancer patients
.
[Wallpaper Discussion]

       At the time of the data cutoff (December 31, 2020), 118 female breast cancer patients were included in the study and received RC48-ADC treatment
.
70 patients (59.
3%) were HER2 positive, and 48 patients (40.
7%) were HER2 low expression
.
At baseline, 77 patients (65.
3%) had liver metastases, and 47 patients (39.
8%) had previously received at least 3 lines of chemotherapy
.

       The results showed that in the HER2-positive subgroup, the confirmed ORRs of patients in the 1.
5, 2.
0, and 2.
5 mg/kg dose groups were 22.
2%, 42.
9%, and 40.
0%, respectively, and the median PFS was 4.
0 months, 5.
7 months, and 6.
3 months, respectively Month
.
In the HER2 low expression subgroup, the confirmed ORR and median PFS were 39.
6% and 5.
7 months.
Among them, the confirmed ORR and median PFS of IHC 2+/FISH- patients were 42.
9% and 6.
6 months, respectively.
IHC 1+ The confirmed ORR and median PFS of the patients were 30.
8% and 5.
5 months, respectively
.

       In terms of safety: the most frequently reported adverse reactions in the study included increased AST (64.
4%), increased ALT (59.
3%), decreased sensation (58.
5%), decreased white blood cell count (48.
3%), and decreased neutrophil count (47.
5%), most of them are grade 1 to 2
.
The most frequently reported (incidence ≥10%) grade ≥3 adverse reactions included decreased neutrophil count (16.
9%), increased γ-glutamyltransferase (12.
7%), and fatigue (11.
9%)
.

       These data indicate that RC48 has shown consistent efficacy in HER2-positive and HER2 low-expressing advanced breast cancer, and no new safety risks have been found
.
Compared with other dose groups, 2.
0 mg/kg Q2W administration showed the best benefit-risk ratio for breast cancer target population
.

       Speaking of ADC, there are currently 12 ADC drugs approved worldwide, as shown in the table below
.
It can be seen that starting from 2019, the global ADC drugs have entered an outbreak period, and three consecutive years have been approved
.
According to a report from Research & Markets, a world-renowned market research company, the ADC market will experience rapid development in the next 10 years.
It is estimated that 7-10 new ADC drugs will be launched, and the ADC market will reach US$10 billion in 2024
.

       However, China currently only approves two ADC drugs, namely Takeda's Vertuximab (2020/05) and Roche's Enmetrastuzumab (2020/01)
.
From the point of view of the target point of action, vedixituzumab is the same as enmetrastuzumab, but enmetrastuzumab is approved for indications: single drug for receiving taxanes combined with trastuzumab Adjuvant treatment of HER2-positive early breast cancer patients who still have aggressive lesions after monoclonal antibody-based neoadjuvant therapy
.
In the future, once Verbutuximab is approved for marketing, there will be no similar products, and the market potential cannot be underestimated
.

       In addition, in addition to Vidicuzumab , there are currently two ADC drugs that have been reported for production in China (see the table below for details)
.
Moreover, Chinese pharmaceutical companies have also deployed the ADC drug market, such as Hengrui Pharmaceuticals, Qilu Pharmaceuticals, Kelun Pharmaceuticals, Biotech, etc.
Among them, Hengrui Pharmaceuticals has 3 ADC drugs in the first phase of clinical trials, and 1 has been declared for clinical use
.
In addition to independent research and development, China's pharmaceutical industry has also successively introduced ADC drugs or jointly developed with other companies.
For example, Leading Pharmaceuticals introduced CD19-targeted ADC drug loncastuximab tesirine from ADC Therapeutics and three other ADC candidate products, Qilu Pharmaceuticals from Korea Biotechnology Company Peptron introduced PAb001-ADC, an ADC candidate product for MUC1, and Sino-American Huadong, a wholly-owned subsidiary of Huadong Medicine, invested in Nuolin Biology's ADC field
.