FDA授予艾伏尼布优先审评资格用于IDH1突变型胆管癌

The FDA has accepted and granted Priority Review status to ivosidenib (Tibsovo)’s supplemental new drug application for the treatment of patients with previously treated IDH1-mutant cholangiocarcinoma. Ivonib is a potent oral targeted inhibitor for cancers with IDH1 gene mutations. IDH1 is a metabolic enzyme whose genetic mutations are present in a variety of tumors, including acute myeloid leukemia, cholangiocarcinoma, and glioma.

Currently, ivonib is approved as a monotherapy for the treatment of patients with IDH1-mutant relapsed or refractory acute myeloid leukemia (AML), as well as patients 75 years or older with newly diagnosed IDH1-mutant AML who have comorbidities that preclude intensive induction therapy. Cholangiocarcinoma refers to a malignant tumor originating from the extrahepatic bile duct, including the bile duct from the portal area to the lower end of the common bile duct. The cause may be related to bile duct stones, primary sclerosing cholangitis and other diseases.

The application is based on results from the Phase 3 ClarIDHy trial (NCT02989857), which tested ivonib versus placebo in the treatment of histologically confirmed IDH1-mutated cholangiocarcinoma that is refractory to curative resection, transplantation, or ablation.

The primary endpoint of the multicenter, randomized, double-blind trial was progression-free survival (PFS), and its PFS results were released last year. The results showed that the benefit of the ivosidenib group (n=124) was statistically significant compared with the placebo group (n=61). The ivonib group reduced the risk of disease progression or death by 67%, with a median PFS of 2.7 months, compared with a median PFS of 1.4 months in the placebo group (HR, 0.37; 95% CI, 0.25-0.54; P<0.0001). At 6 months and 12 months, the PFS rates in the ivonib group were 32% and 22%, respectively.

At the 2021 Gastrointestinal Cancer Symposium, a final analysis of overall survival (OS) showed that the ivonib arm reduced the risk of death by 21% compared with the placebo arm, with a median OS of 10.3 months versus 7.5 months (HR, 0.79; 95% CI, 0.56-1.12; one-sided P=0.093). At 6 months, the corresponding OS rates in the two groups were 69% and 57%, respectively; at 12 months, they were 43% and 36%, respectively.

In a prespecified analysis adjusted for crossover from the control group to the ivosidenib group, patients in the placebo group had a median OS of 5.1 months (HR, 0.49; 95% CI, 0.34-0.70; one-sided P<0.0001). Based on initial study results, ivosidenib was well tolerated. Serious adverse events (AEs) occurred in 30% of patients in the ivosidenib group, 2% of which were considered treatment-related. In contrast, 22% of patients in the placebo group experienced serious adverse events, none of which were related to treatment.

The selected patients were randomized in a 2:1 ratio to receive oral ivosidenib 500 mg or corresponding placebo treatment, once a day, in a 28-day cycle. If the researchers find that patients in the placebo group have radiological progression, such patients will be allowed to cross over to the ivosidenib group.

Susan, Vice President of Clinical Development and Global Development Head of Cancer Metabolism, Servier Pharmaceuticals Dr. Pandya said: "Currently, there are no FDA-approved systemic therapies for the treatment of IDH1-mutant cholangiocarcinoma, and chemotherapy options are limited for advanced patients. For these patients, this FDA priority review designation is an important milestone."

References: https://www.cancernetwork.com/view/ivosidenib-earns-priority-review-for-idh1-mutated-cholangiocarcinoma-after-prior-therapy