Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Ivosidenib Oral Tablet, Ivosidenib 500mg, Ivosidenib 500mg Oral Tablet
Ivosidenib · 6 trials · 7 indications
From randomization until BICR confirmed progressive disease or death due to any cause, whichever occurs first
Adverse events (AEs) will be graded according to the CTCAE v5.0
Adverse events (AEs) will be graded according to the CTCAE v5.0
Infection rates will be summarized by classification and will include a count and proportion.
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.
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.
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.
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.
Total number of AEs that result in discontinuation from treatment or death. AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Listing of all laboratory hematology, coagulation, and chemistry data with values flagged as abnormal to show the corresponding NCI-CTCAE grades and the classifications relative to the laboratory normal ranges.
Abnormalities will be classified by using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 grading scale or the low/normal/high classifications based on laboratory normal ranges. Shift tables using NCI-CTCAE grades to compare baseline to the worst on-treatment value will be used. For laboratory tests, including hematology, coagulation, and chemistry, where NCI-CTCAE grades are not defined, shift tables using the low/normal/high \[low and high\] classification to compare baseline to the worst on treatment may be generated. On-treatment is considered from Day 1 of Cycle 1 through 28 days after the last dose.
Vital signs include systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature.
On-treatment is considered from Day 1 of Cycle 1 through 28 days after the last dose. Vital signs include systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature.
Proportion of subjects who are alive and progression-free (using RECIST v1.1) at 6 months after Day 1 (C1D1) per Independent Radiology Center (IRC)
Will be evaluated according to a modified version of the IWG 2006 Criteria for Hematologic Improvement for patients with MDS on clinical trials * Erythroid response (pretreatment, \<11 g/DL) * Hemoglobin (Hgb) increase by ≥1.5 g/dL * Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 weeks, compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for an Hgb of ≤9.0 g/dL pretreatment will count in the RBC transfusion response evaluation * Platelet response (pretreatment, \<100 x 10\^9/L) * Absolute increase of ≥30 × 10\^9/L for patients starting with \>20 × 10\^9/L platelets. * Increase from \<20 × 10\^9/L to \>20 × 10\^9/L and by at least 100%. * Neutrophil response (pretreatment, \<1.0 x 10\^9/L): * At least 100% increase and an absolute increase \>0.5 × 10\^9/L. If pegfilgrastim being used prior to initiation of study, define response as no longer requiring pegfilgrastim to maintain ANC \>500.
| Arm | Type | Description |
|---|---|---|
| Ivosidenib | EXPERIMENTAL | Taken continuously until BICR-confirmed disease progression, unacceptable toxicity, confirmed pregnancy, death, withdrawal of consent, lost to follow-up, or the Sponsor ends the study (estimated average treatment duration of two years). |
| Placebo | PLACEBO_COMPARATOR | Taken continuously until BICR-confirmed disease progression, unacceptable toxicity, confirmed pregnancy, death, withdrawal of consent, lost to follow-up, or the Sponsor ends the study (estimated average treatment duration of two years). Participants randomized to the placebo arm who experience BICR-confirmed disease progression and meet the crossover eligibility criteria will be given the opportunity to cross over and receive ivosidenib. |
| Open-Label Ivosidenib in combination with Azacitidine | EXPERIMENTAL | All participants will receive both Ivosidenib and Azacitidine for a maximum of 28 cycles. Each cycle will be 4 weeks or 28 days long. Ivosidenib will be taken continuously throughout each cycle and Azacitidine will be taken only for 7 days at the beginning of each cycle. |
| Open-Label Ivosidenib | EXPERIMENTAL | 250 mg Tablets |
| Group 1 - Moderate Hepatic Impairment (HI) | EXPERIMENTAL | - |
| Group 2 - Severe HI | EXPERIMENTAL | - |
| Group 3 - Severe Renal Impairment (RI) | EXPERIMENTAL | - |
| Group 4 - Adequate hepatic function | EXPERIMENTAL | - |
| Group 5 - Adequate renal function | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Ivosidenib 500mg | DRUG | Provided as tablets, taken orally as two 250mg tablets once daily. |
| Placebo | DRUG | Provided as tablets, taken orally once daily. |
| Ivosidenib 500mg Oral Tablet | DRUG | Provided as tablets, taken orally as two 250mg tablets once daily. |
| Azacitidine | DRUG | Administered subcutaneously (SC) or intravenously (IV) at a dose of 75mg/m2/day for 7 days, either consecutively on Days 1-7 or discontinuously for Days 1-5 and 8-9 of each cycle. The 7 days of administration will occur at the beginning of every 4 week-long cycle. |
| Ivosidenib Oral Tablet | DRUG | Ivosidenib 500 mg |
| Ivosidenib | DRUG | Subjects will take 2 tablets (500 mg total) orally once daily. |
Inclusion Criteria: * Have a histopathological diagnosis (fresh or banked tumor biopsy sample collected within the last 3 years) consistent with locally advanced or metastatic conventional chondrosarcoma Grades 1, 2, or 3 and not eligible for curative resection. * Have at least one BICR-confirmed m...
Ivosidenib is an investigational small molecule being studied for several IDH1-mutated cancers, including acute myeloid leukemia, cholangiocarcinoma, and other IDH1-mutated malignancies. It is also being evaluated for clonal cytopenia of undetermined significance and locally advanced or metastatic conventional chondrosarcoma with an IDH1 mutation.
Ivosidenib targets the IDH1 enzyme. It is an inhibitor of mutant IDH1, which is a molecular target in certain cancers. By inhibiting this enzyme, the drug aims to interfere with the metabolic pathways that drive tumor growth in IDH1-mutated malignancies.
Ivosidenib is being developed by Tango Therapeutics, Inc., a biopharmaceutical company traded on the stock exchange under the ticker symbol TNGX. The company is conducting clinical trials to evaluate the drug's safety and efficacy in various oncology indications.
Ivosidenib is in Phase 3 clinical development for cholangiocarcinoma, as part of an early access study. It is also being studied in Phase 2 trials for clonal cytopenia of undetermined significance and cholangiocarcinoma, and in a Phase 1 trial for IDH1-mutated malignancies with hepatic or renal impairment.
Ivosidenib is being studied in several clinical trials, including NCT05030441 for clonal cytopenia of undetermined significance, NCT05876754 for pretreated cholangiocarcinoma, NCT06081829 for Japanese patients with cholangiocarcinoma, and NCT07006688 for IDH1-mutated malignancies with hepatic or renal impairment.
Ivosidenib is also known as Ivosidenib plus oral azacitidine, Ivosidenib plus azacitidine, and Ivosidenib oral tablet. These names refer to the same drug, which is being investigated for use in combination with azacitidine in certain treatment regimens.