The phase 3b ProvIDHe study has provided compelling real-world evidence supporting the efficacy of ivosidenib (Tibsovo) in patients with IDH1-mutated cholangiocarcinoma, with data presented at the 2025 ESMO Gastrointestinal Cancers Congress confirming the drug's clinical benefit outside of controlled trial settings.
Survival Outcomes Validate Clinical Utility
Initial data from ProvIDHe revealed that the median progression-free survival (PFS) in the full analysis set (n = 262) was 4.7 months (95% CI, 3.5-5.7). The 3-, 6-, and 12-month PFS rates were 64.2%, 40.1%, and 28.2%, respectively. Additionally, the median overall survival (OS) was 15.5 months (95% CI, 12.7-not evaluable), with 3-, 6-, and 12-month OS rates of 88.3%, 80.3%, and 60.0%, respectively.
"This interim analysis gave us the preliminary outcomes of the ProvIDHe study, which [enrolled] a phase 3b, real-world population," said John Bridgewater, MRCP, PhD, FRCP, clinical professor in the Research Department of Haematology at University College London. "The [median] PFS and OS are reassuringly good and confirm and support the original dataset from [the phase 3] ClarIDHy study."
Study Design and Patient Population
ProvIDHe was an open-label, international, early-access study of ivosidenib for adult patients with locally advanced or metastatic IDH1-mutated cholangiocarcinoma who had received at least 1 prior line of therapy. Patients also needed to have an ECOG performance status of 0 or 1, a QTcF interval of less than 450 milliseconds, and adequate bone marrow, hepatic, and renal function.
The study enrolled 285 patients across 80 sites in 15 countries. Patients received oral ivosidenib at 500 mg once daily in 28-day treatment cycles, with treatment continuing until unacceptable toxicity or when ivosidenib became accessible via prescription.
At baseline, the median age was 62.0 years (range, 31-90). Most patients were female (56.9%), had an ECOG performance status of 1 (51.9%), had an intrahepatic cholangiocarcinoma primary site (89.7%), and had advanced or metastatic disease (74.8%).
Heavily Pretreated Patient Population
The median number of prior lines of therapy for advanced or metastatic disease was 2 (range, 1-6), with patients having received 1 (39.3%), 2 (27.1%), or more than 2 (22.9%) prior lines. Previous treatments included cisplatin-gemcitabine plus immunotherapy (42%), cisplatin-gemcitabine (40.1%), FOLFOX (leucovorin, fluorouracil, and oxaliplatin; 17.6%), FOLFIRI (5-fluorouracil, leucovorin, and irinotecan; 10.3%), gemcitabine monotherapy (8.4%), and other regimens (18.7%).
Response and Disease Control Rates
Additional findings from ProvIDHe revealed that the objective response rate per RECIST 1.1 criteria was 5.7% (95% CI, 3.2%-9.3%), with all responses being partial. Patients experienced stable disease at a rate of 45.8% and disease progression at a rate of 23.7%. The median duration of response was 10.1 months (95% CI, 3.0-not evaluable), and the disease control rate was 51.5%.
Regulatory Context and Future Implications
In August 2021, the FDA approved ivosidenib for the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma harboring an IDH1 mutation as detected by an FDA-approved test. The regulatory decision was supported by data from ClarIDHy, which demonstrated that ivosidenib led to a 63% reduction in the risk of death or disease progression versus placebo (HR, 0.37; 95% CI, 0.25-0.54; P < .0001).
"[ProvIDHe] is ongoing, and more data will be released [in the future]," Bridgewater concluded, indicating that additional analyses from this real-world evidence study will provide further insights into ivosidenib's clinical utility in routine practice.
