TIBSOVO is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA-approved test with...Locally Advanced or Metastatic Cholangiocarcinoma...Locally advanced or metastatic cholangiocarcinoma who have been previously treated.

Ivosidenib is recommended for the treatment of patients with CCA and IDH1 mutations who have progressed after ≥1 prior line of systemic therapy [I, A; ESMO-MCBS v1.1 score: 2; ESCAT score: I-A; FDA approved, not EMA approved].

Biliary Tract Cancer: Useful in Certain Circumstances…For cholangiocarcinoma with IDH1 mutations...Ivosidenib

Servier...announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion and recommended granting a marketing authorization for Tibsovo® (ivosidenib tablets) - an inhibitor of the mutated isocitrate dehydrogenase-1 (IDH1) enzyme - for two indications:...in monotherapy, for the treatment of adult patients with locally advanced or metastatic IDH1-mutated Cholangiocarcinoma, previously treated by at least one prior line of systemic therapy....The positive CHMP opinion is based on clinical data from the AGILE (AML) and ClarIDHy (CCA) studies.

In this phase 3 randomized clinical trial including 187 previously treated patients with advanced cholangiocarcinoma with IDH1 mutation...ivosidenib was well tolerated and resulted in a favorable OS benefit vs placebo

As of 31 May 2020, ̃780 pts were prescreened for an IDH1 mutation...Median OS (mOS) was 10.3 months for IVO….IVO was well tolerated and resulted in a favorable OS trend vs PBO despite a high rate of crossover. These data – coupled with statistical improvement in PFS, supportive quality of life data, and favorable safety profile – demonstrate the clinical benefit of IVO in advanced mIDH1 CCA.

Servier Pharmaceuticals...announced that the U.S. Food and Drug Administration (FDA) has accepted the company's supplemental New Drug Application (sNDA) for TIBSOVO (ivosidenib tablets) as a potential treatment for patients with previously treated IDH1-mutated cholangiocarcinoma...The sNDA was granted Priority Review, which accelerates the review time from 10 months to a goal of 6 months from the day of filing acceptance.

Pts with mIDH1 CCA were randomized 2:1 to IVO (500 mg PO QD) or matched PBO...IVO was well tolerated and resulted in a favorable OS trend vs PBO despite a high rate of crossover. These data – coupled with statistical improvement in PFS, supportive quality of life data, and favorable safety profile – demonstrate the clinical benefit of IVO in advanced mIDH1 CCA.

NON-SUPPORTIVE EVIDENCE: Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, today announced the results of the final overall survival (OS) analysis from its global Phase 3 ClarIDHy trial of TIBSOVO® (ivosidenib tablets) in previously treated cholangiocarcinoma patients with an isocitrate dehydrogenase 1 (IDH1) mutation. A consistent trend in improved OS was observed in patients treated with TIBSOVO® compared to those randomized to placebo, but was not statistically significant.

Progression-free survival was significantly improved with ivosidenib compared with placebo, and ivosidenib was well tolerated. This study shows the clinical benefit of targeting IDH1 mutations in advanced, IDH1-mutant cholangiocarcinoma.

Primary endpoint (PFS by central review) was met: HR = 0.37 (95% CI 0.25, 0.54; p < 0.001); median PFS was 2.7 (IVO) vs. 1.4 (PBO) mo. PFS rates at 6 and 12 mo were 32.0% and 21.9% in IVO arm...IVO resulted in significant improvement in PFS and favorable OS trend vs. PBO....first pivotal study demonstrating the clinical benefit of targeting mIDH1 in pts with advanced mIDH1 CC.

...Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most recent banked tumor tissue available) based on central laboratory testing (R132C/L/G/H/S mutation variants tested)...

Ivosidenib stimulates a hepatocyte differentiation program in mIDH1 IHCC, a phenotype associated with clinical benefit.

...73 patients with mIDH1 cholangiocarcinoma were enrolled and received ivosidenib…Median progression free survival was 3·8 months (95% CI 3·6-7·3), 6-month progression-free survival was 40·1% (28·4-51·6), and 12-month progression-free survival was 21·8% (12·3-33·0).

In this study, we report the first real-world experience including eight patients with previously treated locally advanced or metastatic IDH1-mutated CCA treated with ivosidenib....The disease control rate was 62.5%, with two patients achieving a partial response (25%)...

...a 43-year-old man in reduced physical condition...NGS of the tumor tissue identified the pathogenic IDH1 mutation...Ivosidenib led to a substantial improvement of patient´s overall physical condition and displayed antitumoral activity and tolerable safety profile in a patient with Maffucci syndrome associated CCa.