-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
CompilationFan Dongdong
Recently, according to foreign media reports, the Independent Data Monitoring Committee (IDMC) believes that GlaxoSmithKline and Merck’s PD-L1/TGF-β anti-bintrafusp alfa combined with gemcitabine and cisplatin are used in the first-line treatment of locally advanced stages.
Or after patients with metastatic biliary tract cancer (BTC) are unlikely to reach the primary end point of overall survival (OS), Merck said it will stop the phase 2 INTR@PID BTC 055 trial of this therapy
.
In February 2019, Merck and GlaxoSmithKline reached a cooperation on the research and development of bintrafusp alfa (M7824) in refractory cancer.
The two pharmaceutical giants signed a global cooperative development agreement totaling US$4.
2 billion
.
This therapy is a first-of-its-kind dual-function immunotherapy that can simultaneously block the two immunosuppressive pathways of TGF-β and PD-L1 in the tumor microenvironment, relieve the suppression of the immune system, and improve the immune system's killing effect on cancer cells.
However, the subsequent development of bintrafusp alfa, which was highly expected, was not as expected.
2021 is definitely a year of setbacks for this therapy
.
In mid-January of this year, bintrafusp alfa was used to treat stage II patients with solid tumors who have received immune checkpoint inhibitors (ICB) and advanced microsatellite instability (MSI-H)/mismatch repair defects (dMMR) (NCT03436563) The study, because it did not show anti-tumor activity, the final test ended in failure
.
In late January this year, the Independent Data Monitoring Committee also recommended that the INTR @PID Lung 037 clinical trial of this therapy in non-small cell lung cancer be stopped because the study is unlikely to reach the common primary endpoint of progression-free survival (PFS)
.
The failure of the trial seems to have also ended bintrafusp alfa's opportunity to compete with Keytruda
In March, the phase II INTR@PID BTC 047 that used bintrafusp alfa alone for the second-line treatment of locally advanced or metastatic biliary tract cancer (BTC) failed to reach the primary endpoint again, and the trial had to be terminated again
.
Merck's announcement of the termination of the biliary tract cancer trial was very brief, and the company did not provide information on the follow-up plan for bintrafusp alfa
.
However, in an earlier statement, Merck detailed bintrafusp alfa's huge clinical plan, including trials for breast, urothelial cancer and cervical cancer, including bintrafusp alfa combined with chemotherapy for second-line treatment of cervical cancer and HMGA2 positive three.
Over time, GlaxoSmithKline’s bet on Merck’s bintrafusp alfa has become worse and worse after repeated trials of the drug have failed
.
It is worth noting that the trial failure of this therapy has also been interpreted by the outside world as another example of the failure of GlaxoSmithKline's reform
It is reported that M7824 can inhibit the PD-1/PD-L1 pathway and exert the killing effect of T cells on tumor cells, while inhibiting the TGF-β pathway, thereby inhibiting the proliferation of tumor cells and promoting their apoptosis
.
According to the Phase I clinical data published by Merck in the American Society of Clinical Oncology in 2018, in the non-small cell cancer patient population, when the dose of bintrafusp alfa is 500 mg, the overall remission of PD-L1+ (≥1%) patients The rate was 22.
6%, and the overall response rate for patients with high PD-L1 expression (≥80%) was 33.
3%
.
At a dose of 1200 mg, the overall remission rate of PD-L1+ (≥1%) patients reached 40.
7%, and the overall remission rate of PD-L1 high expression (≥80%) patients was 71.
4%
.
The amazing results of the initial trials have also allowed many domestic pharmaceutical companies to follow up the PD-L1/TGF-β double antibody research
.
According to data, domestic pharmaceutical companies including Hengrui Pharmaceutical, Junshi Biology, and Zhengda Tianqing have entered the pit to carry out clinical trials
Source: Medical notes (statistics as of July 5, 2021)
However, despite more than 40 studies involving this therapy in the FDA clinical trial database, no indication for bintrafusp alfa is currently approved
.
Coupled with the collapse of multiple clinical trials of the drug in recent years, this can't help but re-examine the value of PD-L1/TGF-β antibodies?
Reference source:
1.
2.
3.
4.
