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On May 12, the CDE official website showed that Genting Pharmaceuticals submitted a listing application for Trop-2 ADC product-Trodelvy (gosartuzumab for injection) for metastatic triple-negative breast cancer that has received at least 2 therapies in the past (MTNBC) Adult patients
.
Goxatuzumab is planned to be included in the priority review channel
Screenshot from CDE official website
Introduction to Trop-2 target
The full name of Trop-2 is human trophoblast cell surface antigen 2
.
Studies have found that TROP-2 is highly expressed in various human epithelial cancers, including breast cancer, lung cancer, gastric cancer, colorectal cancer, pancreatic cancer, prostate cancer, cervical cancer, head and neck cancer and ovarian cancer
Trodelvy is a first-in-class anti-Trop-2 antibody drug conjugate (ADC).
It is an ADC formed by linking an antibody targeting Trop-2 with the active metabolite SN-38 of the chemotherapeutic drug irinotecan.
Trodelvy was approved by the FDA on April 22, 2020 for the treatment of adult patients with metastatic triple-negative breast cancer who have previously received more than two therapies.
It is the world's first ADC drug approved for the treatment of triple-negative breast cancer.
Its mechanism of action is mainly The active metabolite govitecan (SN-38) of the clinically commonly used chemotherapy drug irinotecan is targeted and delivered to the solid tumor lesion through the monoclonal antibody Sacituzumab, which specifically targets Trop-2, and exerts a chemical toxicity and killing effect
.
Trodelvy mechanism of action, picture from 2020ESMO
This approval is based on an international, open-label, phase III ASCENT study, enrolling a total of 529 unresectable locally advanced or metastatic TNBC patients who have previously received at least two therapies
.
In the study, patients were randomly divided into 2 groups, one group received Trodelvy and the other group received chemotherapy selected by the doctor
The results showed that the study reached the primary and key secondary endpoints: Compared with the chemotherapy group, the Trodelvy group had a statistically significant improvement in PFS (median PFS: 4.
7 months vs 1.
7 months), and a significant risk of disease progression Reduced by 57% (HR=0.
43, 95%CI: 0.
35-0.
54, p<0.
0001)
.
In addition, the study also reached key secondary endpoints: compared with chemotherapy group, the Trodelvy group had a statistically significant improvement in OS (median OS: 11.
In terms of safety, the toxicity profile of Trodelvy is consistent with the toxicity profile shown on the previous FDA-approved label
.
Trodelvy’s most common grade ≥3 adverse events include: neutropenia (52% vs 34%), diarrhea (11% vs 1%), leukopenia (11% vs 6%) and anemia (9 % Vs 6%)
TNBC accounts for about 10% to 15% of breast cancer cases.
Compared with other breast cancer subtypes, its recurrence rate is higher and the prognosis is worse
.
It is estimated that only 12.
Current status of domestic Trop2 R&D
On March 4 this year, Biotech announced the termination of the Phase II ADC drug BAT8003.
It is worth mentioning that Pfizer also abandoned the development of its anti-Trop2 ACD drug PF-06664178 in 2016
.
However, the Trop2 project independently developed by two domestic companies is undergoing clinical trials, namely: SKB264 from Kelun and JS108 from Shanghai Junshi Biotech
.
Colum
Antibody-conjugated drug (ADC) is the key layout of Kelun Pharmaceuticals.
Among them, A166 for injection and SKB264 for injection are both new Chinese and American drugs
.
A166 for injection is the third-generation anti-HER2-ADC, intended to treat HER2-positive breast cancer, gastric cancer and other malignant tumors.
SKB264 achieves a high toxin load through a new coupling method.
Preclinical research data shows that it has significant anti-tumor activity in TROP-2 positive breast, gastric, lung, and colorectal cancer animal models, and has good safety and tolerability.
Sex
.
SKB264 was approved by the U.
S.
FDA for clinical trials on August 23, 2019, and received a clinical trial notification from the National Food and Drug Administration in 2020.
It is the second innovative ADC drug to achieve both China and the United States after A166 for injection
.
Jun Shi
In December 2019, Junshi Biotechnology obtained the rights and interests of Duoxi Biologics DAC-002 in Japan, South Korea and other Asian countries at a price of 30 million yuan in advance + 270 million yuan in milestone amount
.
DAC-002 is a recombinant humanized anti-Trop2 monoclonal antibody-Tub196 coupling agent for injection
.
In July 2020, Junshi Biotech's JS108 (DAC-002) was approved and issued by the National Medical Products Administration in the "Drug Clinical Trial Approval Notice", allowing it to carry out clinical trials for the treatment of advanced solid malignant tumors
.
After decades of accumulation of ADC drugs, it has finally begun to show an explosive trend
.
The breakthrough of HER2, Trop2 and other targets has focused more resources on the entire ADC field.
In the next few years, more and more new ADC targets that achieve clinical breakthroughs will emerge
.
Reference source:
1.
https:// 2.
https:// 3.
Trerotola M, Cantanelli P, Guerra E, et al.
Upregulation of Trop-2 quantitatively stimulates human cancer growth.
Oncogene.
2013;32(2): 222-233.