A Phase 3b research study to consolidate the data that ivosidenib is safe and effective in adult patients with previously treated, locally advanced, or metastatic cholangiocarcinoma (CCA). All patients who meet inclusion criteria will be enrolled to receive ivosidenib tablets orally once daily for 28 day cycles, continuing as long as clinical benefit and consent for participation is maintained. There will be a minimum of 6 study visits from screening until the final follow-up, if one cycle of treatment is completed and consent is maintained through 18 months of follow-up. Each additional cycle completed will add one study visit, on the first day of each cycle.
Diagnosis of nonresectable or metastatic Cholangiocarcinoma (CCA), not eligible for curative-intent resection, transplantation, or ablative therapies
Have a documented IDH1 R132C, R132L, R132G, R132H, or R132S gene-mutated disease
Have tried at least 1 prior type of systemic therapy for CCA, and have recovered from any side effects
Female patients of childbearing potential must have a negative blood pregnancy test prior to starting treatment and must agree to use 2 forms of contraception from the time they enroll to 1 month after their last dose of study drug
Received a prior IDH1 inhibitor
Have received a transplant
Have received systemic cancer treatment or radiotherapy within 2 weeks prior to Day 1 of Cycle 1
Have received hepatic radiation, chemoembolization, and radiofrequency ablation within 4 weeks prior to Day 1 of Cycle 1
Single group
Ivosidenib Oral Tablet
DrugIvosidenib 500 mg
Number of Adverse Events (AEs) from Day 1 of Cycle 1 through 28 days after last study treatment
AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. All reported AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA), using the latest version.
Number of Serious Adverse Events (SAEs) during the study treatment period (from Day 1 of Cycle 1 through the last study treatment intake or withdrawal of consent, whichever comes first).
SAEs related to study drug will be collected irrespective of the time of onset. AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Number of QT prolongation events during electrocardiogram (ECG) assessed as Grade 2 or worse occurring from Day 1 of Cycle 1 through 28 days after last study treatment
QT interval, using Fridericia's formula \[QTcF\], to average QTc interval \> 480 to 500msec (Grade 2) or worse, as seen during an ECG. This is classified as an Adverse Event of Special Interest (AESI) for this study.
Change in Eastern Cooperative Oncology Group (ECOG) performance status (PS) score from baseline to worst value out of the post-baseline assessments.
ECOG PS scoring consists of Grade 0 - 5, with 0 being the patient is fully active and 5 being the patient is dead. Descriptive statistics of ECOG PS over time will be summarized by frequency. Shift tables may be provided for ECOG PS from baseline to worst value of post-baseline assessments.
Progression-free survival (PFS) time beginning at enrollement
PFS is defined as the time from the date of enrollment to the date at which the disease escalates or progresses. It will be assessed using the Kaplan-Meier (KM) method curves and estimates. This will be based on tumor assessments conducted by the investigator according to local clinical practice.
Overall survival (OS)
OS is defined as the time from date of enrollment to the date of death due to any cause. It will be assessed using the Kaplan-Meier (KM) method curves and estimates.
Duration of response (DOR)
DOR is defined as the time from the date of response to either progression or death. It will be assessed using the Kaplan-Meier (KM) method curves and estimates. This will be based on tumor assessments conducted by the investigator according to local clinical practice.
Time to response (TTR)
TTR is defined as the time from the date of enrollment to the date of response. It will be assessed using the Kaplan-Meier (KM) method curves and estimates. This will be based on tumor assessments conducted by the investigator according to local clinical practice.
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