The Lynx Group
Cholangiocarcinoma News

Tibsovo First Targeted Therapy FDA Approved for Advanced or Metastatic CCA with IDH1 Mutation

September/October 2021, Vol 2, No 3

On August 25, 2021, the FDA approved ivosidenib (Tibsovo; Servier Pharmaceuticals), an oral IDH1 inhibitor, for the treatment of adults with previously treated, locally advanced or metastatic cholangiocarcinoma (CCA) and an IDH1 mutation, as detected by an FDA-approved test. The FDA granted ivosidenib a priority review for this indication and an orphan drug designation.

On the same day, the FDA also approved the Oncomine Dx Target Test, as a companion diagnostic test for selecting patients with CCA whose disease harbors the IDH1 mutation to receive treatment with ivosidenib.

Ivosidenib was previously approved by the FDA for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) and IDH1 mutation, as detected by an FDA-approved test, and for patients with newly diagnosed AML and IDH1 mutation who are aged ≥75 years or who have comorbidities that preclude the use of intensive induction chemotherapy.

Up to 20% of patients with CCA have IDH1 mutation, which is associated with poor prognosis.

“Patients living with IDH1-mutated cholangiocarcinoma, especially those whose disease progresses following chemotherapy, are in urgent need of new treatment options,” said Rachna T. Shroff, MD, MS, Associate Professor of Medicine, University of Arizona, and Chief of GI Medical Oncology at the University of Arizona Cancer Center, Tucson. “In addition to an acceptable safety profile, Tibsovo demonstrated an impressive, significant benefit in progression-free survival, underscoring its importance as a new option for patients battling this aggressive cancer,” Dr Shroff added.

The FDA approval was based on results from the ClarIDHy clinical trial, a phase 3, multicenter, randomized, double-blind, placebo-controlled study. This study included 185 adults with locally advanced or metastatic CCA and an IDH1 mutation who had previously received up to 2 treatment regimens, including at least 1 gemcitabine- or 5-fluorouracil–containing regimens. The 185 patients in the ClarIDHy study received 500 mg oral ivosidenib or placebo once daily, until disease progression or until unacceptable adverse events.

The primary end point was progression-free survival (PFS), as determined by an independent review committee. The results showed a significant improvement in PFS in patients who received ivosidenib versus placebo (95% confidence interval [CI], 0.25-0.54; P <.0001). The difference in overall survival was not significant (95% CI, 0.56-1.12; P = .093).

At a 6-month follow-up, 32% of patients who received ivosidenib remained free of disease progression; by 12 months of follow-up, this rate was 22%.

The study design allowed patients to cross over from the placebo arm to the ivosidenib arm at disease progression. A majority (70%) of the patients in the placebo arm crossed over to the ivosidenib arm after radiographic disease progression.

The most common (≥15%) adverse reactions reported with ivosidenib were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.

“Before today’s approval of Tibsovo, there were no approved targeted therapies available to cholangiocarcinoma patients harboring the IDH1 mutation, and limited chemotherapy options available to patients with advanced disease,” said Stacie Lindsey, Founder and CEO, the Cholangiocarcinoma Foundation. “This approval brings new hope to the cholangiocarcinoma community, and we are excited that this much-needed new therapeutic option is being made available to patients,” she emphasized.

The recommended dose of oral ivosidenib is 500 mg once daily, taken with or without food, until disease progression or until unacceptable adverse events.

Related Items

FDA Grants TT-00420, a Multi-Kinase Inhibitor, Fast-Track Review for Cholangiocarcinoma
Web Exclusives
On November 3, 2021, TransThera Sciences announced that the FDA granted its investigational drug, TT-00420, a spectrum-selective multi-kinase inhibitor, a fast-track designation for the treatment of patients with cholangiocarcinoma (CCA) who have no available standard treatment options. In preclinical studies, TT-00420 has shown high activity in a variety of FGFR mutations.
Hot Topics in Cholangiocarcinoma and Biliary Tract Cancers: ASCO Highlights
September/October 2021, Vol 2, No 3
At the CCA Summit during the 2021 Annual Meeting of the American Society of Clinical Oncology (ASCO), Mitesh J. Borad, MD, Associate Professor of Medicine, Mayo Clinic, Phoenix, AZ, reviewed some of the key topics presented at ASCO 2021 related to cholangiocarcinoma (CCA) and other biliary tract cancers. Before turning to the specific presentations, Dr Borad welcomed the May 28, 2021, FDA approval of infigratinib (Truseltiq) for patients with advanced or metastatic CCA and FGFR2 fusions or rearrangements. Infigratinib follows pemigatinib (Pemazyre) as the second targeted therapy now available for this patient population.
Important Role of Screening for Genomic Alterations in Cholangiocarcinoma
September/October 2021, Vol 2, No 3
Comprehensive molecular profiling has demonstrated a diverse landscape of oncogenic genomic alterations in cholangiocarcinoma (CCA), which are often the drivers of CCA. In a recent review article, Tanios S. Bekaii-Saab, MD, FACP, Vice Chair and Section Chief for Medical Oncology, Department of Internal Medicine, Mayo Clinic Cancer Center, Phoenix, AZ, and colleagues provided an overview of the molecular heterogeneity of CCA, discussing the role of molecular tests for the diagnosis of patients with intrahepatic CCA, and the implications of the genomic alterations in the treatment of patients with this aggressive disease.
Role of Intraductal Treatment and Endoscopic Oncologists in the Management of Unresectable Extrahepatic Cholangiocarcinoma
September/October 2021, Vol 2, No 3
Although cholangiocarcinoma (CCA) is a rare cancer that originates in the bile ducts, its incidence rate continues to rise in the United States, and many patients are diagnosed late, with unresectable tumor and poor prognosis. The majority of patients with extrahepatic CCA, including the perihilar subtype, require referral to a center with expertise in endoscopic retrograde cholangiopancreatography (ERCP) and interventional radiology, because of the complexities in obtaining a definitive diagnosis and durable biliary drainage.
Role of Radiology in Intrahepatic Cholangiocarcinoma Addressed at 2 Interventional Oncology and Radiology Meetings
September/October 2021, Vol 2, No 3
Key topics related to intrahepatic cholangiocarcinoma (CCA) were presented at the 2021 Society of Interventional Oncology (SIO) and the Society of Interventional Radiology (SIR) meetings and were discussed at the CCA Summit. Bruno C. Odisio, MD, FSIR, Interventional Radiologist and Co-Director of Research, Interventional Radiology, M.D. Anderson Cancer Center, Houston, TX, reviewed the findings.
Ivosidenib Approved for Advanced or Metastatic Cholangiocarcinoma
Web Exclusives
Ivosidenib has been approved by the FDA for adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 mutation as detected by an FDA-approved test.
Recent Developments in Genomic-Driven Therapies for Cholangiocarcinoma
June/July 2021, Vol 2, No 2
Personalized medicine has expanded the treatment options for patients with cholangiocarcinoma (CCA). At the 2021 Annual Meeting of the Cholangiocarcinoma Foundation (CCF), Ghassan K. Abou-Alfa, MD, MBA, Professor of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, discussed recent developments in personalized therapies, highlighting genomic alterations that are informing the new therapies for patients with CCA.
FDA Grants Accelerated Approval to Infigratinib for Metastatic Cholangiocarcinoma
June/July 2021, Vol 2, No 2
The FDA granted accelerated approval to the kinase inhibitor infigratinib (Truseltiq) for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma (CCA) that harbors an FGFR2 fusion or other rearrangement.
Futibatinib in Intrahepatic Cholangiocarcinoma with FGFR2 Fusions or Rearrangements: Primary Results of FOENIX-CCA2 Presented at AACR 2021
June/July 2021, Vol 2, No 2
The primary results of the phase 2 FOENIX-CCA2 clinical trial of futibatinib in patients with previously treated intrahepatic cholangiocarcinoma (CCA) and FGFR2 fusions or rearrangements were presented by Lipika Goyal, MD, MPhil, Assistant Professor of Medicine, Massachusetts General Hospital, Boston, at the 2021 Annual Meeting of the American Association for Cancer Research (AACR).
Truseltiq (Infigratinib) New Targeted Therapy FDA Approved for Advanced or Metastatic Cholangiocarcinoma Harboring FGFR2 Alterations
By Loretta Fala
June/July 2021, Vol 2, No 2
Cholangiocarcinoma (CCA) represents a group of heterogeneous cancers that originate in the bile ducts that connect the liver and gallbladder to the small intestine. Although the exact prevalence of CCA is unknown, CCA is a rare cancer; approximately 8000 new cases of CCA are diagnosed annually in the United States.

Subscribe to CCA News

Stay up to date with personalized medicine by subscribing to receive the free CCA News print publication or weekly e‑Newsletter.

I'd like to receive: