Gastric cancer indications take the lead in breaking through the domestic ADC from behind the scenes to the front stage

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On June 9th, Rongchang Biologics' injection vedicitumumab (RC48) was approved by the NMPA for the treatment of patients with locally advanced or metastatic gastric cancer overexpressing HER2 who have received at least two systemic chemotherapy

(1) Vidicuzumab (RC48)

Vidicuzumab (RC48) is a HER2 ADC drug independently developed by Rongchang Biologics, and its trade name is Aidixi

(1) Antibody part: Disitamab, Disitamab is a monoclonal antibody targeting HER2

(2) Linker: Cysteine ​​coupling, the uniformity is greatly improved compared with lysine

(3) Payload: Tubulin inhibitor MMAE, which can block tubulin polymerization.

The approval of RC48 gastric cancer indication is based on a single-arm, open, multi-center phase II pivotal clinical trial

RC48 gastric cancer indication clinical data

Data source: Rongchang Biological

In addition to gastric cancer indications, RC48 also has indications for breast cancer, urothelial cancer, biliary tract cancer, and non-small cell lung cancer

In terms of breast cancer indications, SABCS announced the clinical data of RC48 in positive breast cancer in 2019, with an ORR of 31.

(2) Enhertu (DS-8201)

Enhertu (DS-8201) is a HER2 ADC drug jointly developed by AstraZeneca and Daiichi Sankyo.

The structure of DS-8201 includes:

(1) Antibody: trastuzumab;

(2) Linker: Linker can be cut, with bystander effect;

(3) Payload: Dxd is an innovative DNA topoisomerase inhibitor independently developed by Daiichi Sankyo, and its activity is ten times that of irinotecan (SN-38)

Picture: DS-8201 Structural Design Picture

In breast and stomach cancer indications, DS-8201 has shown unparalleled efficacy

In December 2019, DS-8201 was approved for HER2-positive breast cancer indication.

In January 2021, DS-8201 was approved as an indication for advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma

Good experimental data injected a dose of invigorating the doctor's prescription DS-8201.

Comparison of clinical results between DS-8201 and RC48 in the treatment of gastric cancer

Data source: CSCO, ASCO

(Three) ARX788

ARX788 is a HER2 ADC drug jointly developed and commercialized by Zhejiang Pharmaceutical (New Code Bio) and Ambrx, which is a combination of trastuzumab and AS269

ARX788 structure includes:

(1) Antibody: Trastuzumab

(2) Linker: non-cleavable linker and unnatural amino acid technology, DAR is equal to 2

(3) Payload: AS269 is Ambrx's exclusive cytotoxic drug and a tubulin inhibitor
.

ARX788 structure

Data source: Ambrx

Like RC48 and DS-8201, ARX788 also has gastric cancer indications.
In February 2021, Xinma Bio received the "Drug Clinical Trial Approval Notice" approved and issued by NMPA and agreed to develop its use in gastric cancer and gastroesophageal junction Phase II/III clinical trials for the treatment of adenocarcinoma
.
In March 2021, ARX788 was granted orphan drug designation by the FDA
.

2021ASCO announced the latest clinical progress of ARX788 in the treatment of gastric cancer.
The results of the ACE-Pan tumor-01 test showed that the ORR of ARX788 single-agent treatment reached 67%
.
However, this data is not very comparable.
On the one hand, due to the small number of participants, there are only 3 subjects.
On the other hand, the ACE-Pan tumor-01 test group includes breast cancer, gastric cancer, and non-small cell lung cancer.
Kind of solid tumor patients
.
For the efficacy of ARX788 for gastric cancer indications, subsequent disclosure of efficacy data is still required, but the adverse events of ocular toxicity and pneumonia above grade 3 must be further observed
.

(4) Summary

With the approval of the RC48, the first domestically developed HER2 ADC has officially moved from behind the scenes to the front stage
.
Gastric cancer indications, as the next city of HER2 ADC following breast cancer, deserve special attention
.
At present, the T-DM1 gastric cancer indication has failed.
Rongchang Biologics is expected to quickly seize the market by virtue of its first-mover advantage.
The clinical layout of multiple indications simultaneously highlights the company's long-term wisdom
.
However, DS-8201 will reshape the competitive landscape of the market once it goes on the market with its excellent clinical data
.
In the face of RC48, which is the stumbling block and the DS-8201, ARX788 can only accelerate its research and development and quickly go to market with excellent Phase II clinical data, which may be the key to winning back a city
.