FDA approves Tibsovo for IDH1-mutated cholangiocarcinoma
The FDA approved ivosidenib tablets for adults with previously treated, locally advanced or metastatic IDH1-mutated cholangiocarcinoma.
Cholangiocarcinoma is an aggressive cancer of the bile ducts. An estimated 8,000 people in the United States are diagnosed with cholangiocarcinoma each year, and up to 20% of patients with cholangiocarcinoma harbor IDH1 mutations.
Ivosidenib tablets (Tibsovo, Servier Pharmaceuticals) is an isocitrate dehydrogenase-1 (IDH1) inhibitor approved in the United States for treatment of certain patients with acute myeloid leukemia.
Servier submitted a supplemental new drug application for the cholangiocarcinoma indication based on results of the randomized phase 3 ClarIDHy study.
The trial included 185 adults with locally advanced or metastatic IDH1-mutated cholangiocarcinoma whose disease progressed after one or two prior treatments, including at least one gemcitabine- or 5-FU-containing regimen.
Researchers randomly assigned patients 2:1 to 500 mg ivosidenib once daily or placebo. Treatment continued until disease progression or unacceptable toxicity.
PFS assessed by independent review committee served as the primary efficacy endpoint.
As Healio previously reported, results presented at Gastrointestinal Cancers Symposium showed ivosidenib improved conferred a statistically significant PFS benefit compared with placebo for patients with previously treated IDH1-mutated advanced cholangiocarcinoma (median, 2.7 months vs. 1.4 months; HR = 0.37; 95% CI, 0.25-0.54).
Twenty-two percent of ivosidenib-treated patients achieved 1-year PFS, compared with none in the placebo group.
Seventy percent of patients assigned placebo crossed over to receive ivosidenib upon disease progression.
An analysis unadjusted for crossover showed no statistically significant OS benefit with ivosidenib (median, 10.3 months vs. 7.5 months; HR = 0.79; 95% CI, 0.56-1.12).
The agent appeared well-tolerated. The most common adverse events among ivosidenib-treated patients with cholangiocarcinoma included fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia and rash.
“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, CEO of Servier Pharmaceuticals, said in a company-issued press release. “We are proud to bring to patients the first and only targeted therapy for previously treated IDH1-mutated cholangiocarcinoma.”
The FDA also approved the Oncomine Dx Target Test (Thermo Fisher Scientific) as a companion diagnostic to identify patients with IDH1-mutated cholangiocarcinoma who may be candidates for ivosidenib tablets.