April 21, 2024

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Biliary tract cancer: Innovative dual anti-drugs (Immunity+Targeting)

Biliary tract cancer: Innovative dual anti-drugs (Immunity+Targeting)

Biliary tract cancer: Innovative dual anti-drugs (Immunity+Targeting).   Biliary tract cancer is an aggressive gastrointestinal cancer, and immunotherapy has taken a place in tumor treatment, whether it is a single drug, or a combination of targeted therapies and chemotherapy.

Biliary tract cancer: Innovative dual anti-drugs (Immunity+Targeting)


However, when immunotherapy is used as a single agent, the patient’s objective remission rate is not high, or people who express PD-L1 need to be screened, and other therapies are faced with increased toxicity or non-response. In addition to the combination of drugs, what better way to increase the efficacy of immunotherapy?

A bifunctional immunotherapy brings good news. By adding new anti-tumor targets, one drug with two targets, it is expected to circumvent the limitations of traditional immunotherapy.

Recently, the clinical data of Bintrafusp alfa (M7824), a dual-target broad-spectrum anticancer drug under investigation, is amazing. It is expected to be used as a single-drug therapy to treat locally advanced or metastatic biliary tract cancer (BTC) that has failed or intolerated first-line platinum-based chemotherapy. patient.


▌”Dangerous” Biliary Tract Cancer

Biliary tract cancer (BTC) is an aggressive gastrointestinal cancer that occurs in the biliary tract, including gallbladder cancer and cholangiocarcinoma, accounting for about 3% of all adult cancers.

Over 210,000 people are diagnosed with biliary tract cancer each year in the world, and China has one of the highest incidences of biliary tract cancer in the world.

The early symptoms of biliary tract cancer are not obvious. After the diagnosis of advanced biliary tract cancer, most patients have lost the opportunity for surgery. In addition, they are not sensitive to tumor radiotherapy and chemotherapy, and there is basically no cure. Those who have undergone potentially radical surgery have a high recurrence rate.

For patients with advanced biliary tract cancer with disease progression after first-line chemotherapy, the current standard treatment is gemcitabine-based combination chemotherapy. The treatment options are greatly limited and the efficacy is not ideal. The patient’s survival period is less than 1 year. “Cancer King” pancreatic cancer is even more dangerous.

Moreover, there is currently no approved second-line standard therapy for biliary tract cancer, and the response rate of chemotherapy and immunotherapy in patients with biliary tract cancer is very low.


▌Innovative double antibody: Bintrafusp alfa

Bintrafusp alfa (M7824) is a new type of PD-L1 and TGF-? bispecific antibody drug, which can inhibit the PD-1/PD-L1 pathway and exert T cells to kill tumor cells while inhibiting the TGF-β pathway, thereby inhibiting The proliferation of tumor cells promotes their apoptosis.

Epithelial-mesenchymal transition (EMT) is a marker of tumor progression and drug resistance, plays an important role in biliary tract cancer, and has been proven to be triggered by TGF-β signaling.

Based on this mechanism of action, Bintrafusp alfa has the potential to improve the progression-free survival of patients and reduce the side effects of combination drugs.

In the pre-clinical study, the data of Bintrafusp alfa caused a sensation. All experimental animals responded to it, and the progression-free survival period reached 100%!


▌The clinical data is amazing and the potential is huge!

In a clinical trial involving 159 patients with biliary tract cancer, the follow-up time was 9 months, and the results showed:

The objective response rate (ORR) of patients in the Bintrafusp alfa monotherapy group was 10.1%. It has proved its single-drug efficacy and durability, and its safety is controllable.

Although the study has not reached the predetermined threshold, the ORR of current single-agent immunotherapy for patients with recurrent or metastatic biliary tract cancer expressing PD-L1 is only 5.8%.

This result also allows us to see the potential of Bintrafusp alfa in patients with biliary tract cancer whose treatment needs are not met, and it is expected to become a second-line therapy for this type of patients in the future.

In addition, in a number of phase 1 clinical trials, many cancer patients have received Bintrafusp alfa treatment, involving more than 10 types of pancreatic cancer, lung cancer, and cervical cancer. Among them, some test results are positive, and the next step of research will be continued.







(source:internet, reference only)

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