First targeted drug for Cholangiocarcinoma reducing risk death by 63%!

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First targeted drug for Cholangiocarcinoma reducing risk death by 63%!

First targeted drug for Cholangiocarcinoma reducing risk death by 63%! Cholangiocarcinoma mainly includes gallbladder cancer and intrahepatic cholangiocarcinoma. some countries is one of the countries with the highest incidence of cholangiocarcinoma in the world.

Recently, FDA announced that it will accept a supplementary new drug application (sNDA) submitted by Ivosidenib (Tibsovo), a tablet that targets IDH1, for the treatment of patients with treated cholangiocarcinoma with isocitrate dehydrogenase-1 (IDH1) mutations; at the same time, Granting the drug priority review qualification will greatly shorten the review time of Ivosidenib.

Ivosidenib is an oral targeted inhibitor of IDH1 enzyme. In 2018, Ivosidenib was approved to treat adult patients with IDH1 mutations in relapsed or refractory acute myeloid leukemia, becoming the world’s first drug approved by the FDA for the treatment of IDH1 mutation R/RAML.

▌How to break the dilemma in the treatment of cholangiocarcinoma?

Cholangiocarcinoma is a rare and aggressive cancer, and some countries is one of the countries with the highest incidence of cholangiocarcinoma in the world.

Cholangiocarcinoma mainly includes gallbladder cancer and intrahepatic cholangiocarcinoma, most of which are adenocarcinoma. Because the disease is difficult to detect in the early stage, most of it has reached the late stage when it is diagnosed.

At present, surgery is the most important treatment option for patients with cholangiocarcinoma. However, because advanced patients lose the opportunity for surgery, the first-line treatment is mainly standard chemotherapy. However, the median survival time of many patients is less than 1 year, and the five-year survival rate is almost zero.

Even if some patients can be surgically removed, the recurrence rate of cholangiocarcinoma is very high, even more than 80%.

In recent years, targeted therapy and immunotherapy have brought new dawn to advanced cholangiocarcinoma. In April last year, the FGFR kinase inhibitor Pemigatinib (Pemazyre) was approved for the treatment of patients with FGFR2 fusion/rearrangement and inoperable cholangiocarcinoma, providing the first targeted therapy for patients with first-line chemotherapy or recurrence after surgery select.

▌Oral IDH1 inhibitor: Ivosidenib

IDH1 mutation occurs in approximately 13% of cholangiocarcinoma patients and is another key target gene after FGFR2.

IDH1 is an important metabolic enzyme, mainly present in peroxisomes and cytoplasm. IDH1 mutations are common in a variety of blood cancers and solid tumors such as leukemia, lymphoma, cholangiocarcinoma and colorectal cancer.

At present, there is no approved therapy for IDH1 mutant cholangiocarcinoma, and the available chemotherapy options in advanced patients are limited, and effective innovative therapies are urgently needed.

It is worth mentioning that Ivosidenib has been approved to enter clinical trials in China for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) who have passed the FDA-approved test for IDH1 mutations.

▌The risk of death is reduced by 63%, and the results of targeted therapy are amazing!

This sNDA is based on the positive results of the ClarIDHy Phase 3 clinical trial. ClarIDHy is an ongoing randomized, double-blind, placebo-controlled study that enrolled 187 previously treated patients with IDH1 mutant cholangiocarcinoma.

Patients were randomized to receive Ivosidenib or placebo at a ratio of 2:1. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival (OS), objective response rate, safety and tolerability, etc.

The results published in the journal The Lancet Oncology show that:

Compared with placebo, Ivosidenib reduced the risk of disease progression or death in patients with IDH1 mutant cholangiocarcinoma by 63% (2.7 months VS 1.4 months), reaching the primary endpoint of a significant improvement in progression-free survival.

In addition, Ivosidenib also improves the overall survival of patients. The median OS of the treatment group and placebo group was 10.3 months VS 7.5 months, respectively.

This is the first randomized Phase 3 clinical trial for patients with treated cholangiocarcinoma with IDH1 mutations. Once approved, Ivosidenib will become a targeted therapy approved by the FDA, bringing new hope for such refractory patients.

(source:internet, reference only)

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