FDA Approves Ivosidenib for Patients with IDH1-Positive Cholangiocarcinoma

Ivosidenib has received approval from the FDA for patients with IDH1-mutated cholangiocarcinoma.

The FDA has approved the use of oral ivosidenib (Tibsovo) for the treatment of adult patients with IDH1-mutant cholangiocarcinoma as detected by an FDA-approved test, according to a press release from drug developer, Servier Pharmaceuticals.1

The approval was based on the results of the phase 3 ClarIDHy trial (NCT02989857), in which ivosidenib demonstrated a statistically significant improvement in progression-free survival (PFS; HR, 0.37; 95% CI, 0.25-0.54; P <.001).2 The agent yielded a median PFS of 2.7 months (95% CI, 1.6-4.2) vs 1.4 months in the placebo arm (95% CI, 1.4-1.6). In total, 32% of patients at 6 months and 22% of patients at 12 months remained free from progression or death when receiving ivosidenib.

“Servier has been focused on exploring the significant potential of inhibiting mutant IDH enzymes as a novel approach to treating cancers with high unmet needs, including cholangiocarcinoma,” David K. Lee, chief executive officer at Servier Pharmaceuticals, said in a press release. “We are proud to bring to patients the first and only targeted therapy for previously treated IDH1-mutated cholangiocarcinoma. We are grateful to the patients, caregivers, investigators and study teams who made this achievement possible through their participation in the ClarIDHy clinical trial.”

Ivosidenib’s new drug application was given a priority review by the FDA on May 5, 2021, which helped to accelerate the period of review that is ordinarily given to agents that may offer notable advances in treatment or offer a therapy where no other exists.3

The study protocol allowed patients who were randomized to the placebo arm to cross over to the ivosidenib arm upon disease progression. In total, 70.5% of patients crossed over to receive the experimental agent. Aside from meeting the primary end point of PFS improvement, the study also identified favorable results for the key secondary end point of overall survival (OS). Without adjusting for crossover, the median OS for patients in the ivosidenib arm was 10.3 months (95% CI, 7.8-12.4) and 7.5 months (95% CI, 4.8-11.1) in the placebo arm (HR, 0.79; 95% CI, 0.56-1.12; P = .093).

The most common adverse effects associated with ivosidenib included fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.

“Patients living with IDH1-mutated cholangiocarcinoma, especially those whose disease progresses following chemotherapy, are in urgent need of new treatment options,” Rachna T. Shroff, MD, associate professor of medicine at the University of Arizona, and chief of GI medical oncology at the University of Arizona Cancer Center, said in a press release. “In addition to an acceptable safety profile, [ivosidenib] demonstrated an impressive, significant benefit in [PFS], underscoring its importance as a new option for patients battling this aggressive cancer.”

The FDA also granted pre-market approval to the Oncomine Dx Target Test from Thermo Fisher Scientific as a companion diagnostic for the identification of patients with cholangiocarcinoma harboring IDH1 mutations who may be suitable for treatment with ivosidenib.4


  1. Servier announces FDA approval of TIBSOVO® (ivosidenib tablets) in IDH1-mutated cholangiocarcinoma. News release. Servier Pharmaceuticals. August 25, 2021. Accessed August 25, 2021. https://bit.ly/3DhHGu7
  2. Zhu AX, Macarulla T, Javle MM, et al. Final results from ClarIDHy, a global, phase III, randomized, double-blind study of ivosidenib (IVO) versus placebo (PBO) in patients (pts) with previously treated cholangiocarcinoma (CCA) and an isocitrate dehydrogenase 1 (IDH1) mutation. J Clin Oncol. 2021;39(suppl 3):266. http://bit.ly/2KobGOh.
  3. Servier announces FDA filing acceptance and priority review for TIBSOVO® (ivosidenib tablets) in IDH1-mutated cholangiocarcinoma. News release. Servier Pharmaceuticals. May 5, 2021. Accessed August 25, 2021. https://bit.ly/2Rp2uMW
  4. FDA Approves NGS-Based Companion Diagnostic for Previously Treated IDH1-Mutated Cholangiocarcinoma. News release. Thermo Fisher Scientific. August 25, 2021. Accessed August 25, 2021. https://bit.ly/2UM8XmX
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