Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)

• Sponsor: Agios Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02989857
• Collaborator: (none)
• Enrollment: 187
• Locations: 49
• Arms: 3
• Actual Duration (Months): 50.8
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Study AG120-C-005 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of orally administered AG-120. Participants, all personnel involved in the evaluation of participants' response to treatment (e.g., Investigators, study coordinators, study pharmacists), and designated Sponsor team members will be blinded to study treatment. Participants are required to have a histologically-confirmed diagnosis of isocitrate dehydrogenase-1 (IDH1) gene-mutated cholangiocarcinoma that is not eligible for curative resection, transplantation, or ablative therapies prior to enrollment. IDH1 mutation testing will be performed at participating investigative sites. Participants must have progression of disease and have received at least 1 but not more than 2 prior treatment regimens for advanced disease (nonresectable or metastatic). All participants must have received either a gemcitabine or a 5 fluorouracil (5-FU) based chemotherapy regimen.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cholangiocarcinoma; Metastatic Cholangiocarcinoma	Drug: AG-120; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 187 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients randomized in a 2:1 allocation (AG-120 vs Placebo)Patients randomized in a 2:1 allocation (AG-120 vs Placebo)
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-controlled Study of AG-120 in Previously-treated Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
• Actual Study Start Date: Feb 20, 2017
• Actual Primary Completion Date: Jan 31, 2019
• Actual Study Completion Date: May 17, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: AG-120 Participants received AG-120 500 mg, tablet, orally, once daily (QD) in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 24 months.	Drug: AG-120; Tablet administered orally; Other Names: Ivosidenib
Placebo Comparator: Placebo Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 24 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.	Drug: Placebo; Tablet administered orally
Experimental: After Cross over to AG-120 Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 24 months.	Drug: AG-120; Tablet administered orally; Other Names: Ivosidenib

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) as Determined by the Independent Radiology Committee (IRC) [From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)]

   PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by the IRC using Response Evaluation Criteria in Solid Tumors [RECIST] v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as greater than or equal to (≥)20 percent (%) increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm) or the appearance of 1 or more new lesions.

Secondary Outcome Measures

1. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to approximately 4 years]

2. Percentage of Participants With Laboratory Abnormalities [Up to approximately 4 years]

3. Percentage of Participants With Clinically Significant Vital Signs [Up to approximately 4 years]

4. Eastern Cooperative Oncology Group (ECOG) Performance Status [Up to approximately 4 years]

   The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score classifies participants according to their functional impairment, with scores ranging from 0 to 4. ECOG PS: 0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair.

5. Percentage of Participants With Concomitant Medications [Up to approximately 4 years]

6. Percentage of Participants With Abnormal Electrocardiogram (ECG) Changes [Up to approximately 4 years]

7. Overall Survival (OS) [Up to 52 weeks]

8. Overall Response Rate (ORR) by the Investigator [From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)]

9. ORR as Assessed by the IRC Per RECIST v1.1 [From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)]

10. Duration of Response (DOR) as Assessed by the Investigator [From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)]

11. DOR as Assessed by the IRC Per RECIST v1.1 [From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)]

12. Time to Response (TTR) as Assessed by the Investigator [From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)]

13. TTR as Assessed by the IRC Per RECIST v1.1 [From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)]

14. PFS Per Investigator Assessment [From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)]

15. Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 [Up to approximately 4 years]

    The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single-item assessments (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. Most of the 30 items have 4 response levels (not at all, a little, quite a bit, and very much). Raw scores are converted into scale scores ranging from 0 to 100. For C30-Overall Health and C30-Quality of Life, higher scores indicate better condition.

16. HRQOL: Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21) [Up to approximately 4 years]

    The QLQ-BIL21 contains 21 items in total and each item is a 4-point Likert scale. These 21 items can be grouped into 5 scales (eating symptoms, jaundice symptoms, tiredness, pain symptoms, and anxiety symptoms) and 3 single-item assessments (treatment side-effects, difficulties with drainage bag/tubes, and concerns regarding weight loss). Most of the 21 items have 4 response levels (not at all, a little, quite a bit, and very much). Higher scores indicate better condition.

17. HRQOL: Patient Global Impression of Change (PGI-C) [Up to approximately 4 years]

    The anchor-based questionnaire PGI-C contains the following 3 items (the overall change in the physical functioning since the start of taking the study medication, the overall change in the appetite since the start of taking the study medication, and the overall change in the pain since the start of taking the study medication). The PGI-C is measured using a 7-point Likert scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse.

18. HRQOL: Patient Global Impression of Severity (PGI-S) [Up to approximately 4 years]

    The anchor-based questionnaire PGI-S contains the following 3 items (the severity of the physical functioning decline over the past week, the severity of the appetite decrease over the past week, and the severity of the pain over the past week). The PGI-S is measured using a 7-point Likert scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse.

19. Health Economic Outcomes: 5-level EuroQol Five Dimensions Questionnaire (EQ-5D-5L) [Up to approximately 4 years]

    The EQ-5D-5L contains 5 dimensions (Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression) as well as the EQ visual analogue scale (VAS). EQ-5D-5L consists of 2 components: a descriptive system of the participant's health and a rating of his or her current health state on a 0-100 VAS. The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health.

20. Maximum Observed Plasma Concentration (Cmax) of AG-120 [Day 1 of every cycle up to End of Treatment (EOT) (up to approximately 4 years)]

21. Time to Reach Maximal Plasma Concentration (Tmax) of AG-120 [Day 1 of every cycle up to EOT (up to approximately 4 years)]

22. Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours (AUC0-4) [Day 1 of every cycle up to EOT (up to approximately 4 years)]

23. Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) [Day 1 of every cycle up to EOT (up to approximately 4 years)]

24. Accumulation Ratio Based on AUC0-4 (Racc AUC0-4) [Day 1 of every cycle up to EOT (up to approximately 4 years)]

25. Accumulation Ratio Based on Cmax (Racc Cmax) [Day 1 of every cycle up to EOT (up to approximately 4 years)]

26. Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120 [Day 1 of every cycle up to EOT (up to approximately 4 years)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Be ≥18 years of age.

2. Have a histopathological diagnosis (fresh or banked tumor biopsy sample, preferably collected within the last 3 years) of nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation, or ablative therapies.

3. Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most recent banked tumor tissue available) based on central laboratory testing (R132C/L/G/H/S mutation variants tested).

4. Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1

5. Have an expected survival of ≥3 months.

6. Have at least one evaluable and measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Participants who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, or radiation therapy) are eligible provided measurable disease falls outside of the treatment field or within the field and has shown ≥20% growth in size since post-treatment assessment.

7. Have documented disease progression following at least 1 and no more than 2 prior systemic regimens for advanced disease (nonresectable or metastatic). Participants must have received at least 1 gemcitabine- or 5-FU-containing regimen for advanced cholangiocarcinoma. Participants who have received systemic adjuvant chemotherapy will be permitted provided there is documented disease progression during or within 6 months of completing the therapy.

Exclusion criteria:

1. Received a prior IDH inhibitor.

2. Received systemic anticancer therapy or an investigational agent <2 weeks prior to Day 1 (washout from prior immune based anticancer therapy is 4 weeks). In addition, the first dose of study treatment should not occur before a period ≥5 half-lives of the investigational agent has elapsed.

3. Received radiotherapy to metastatic sites of disease <2 weeks prior to Day 1.

4. Underwent hepatic radiation, chemoembolization, and radiofrequency ablation <4 weeks prior to Day 1.

5. Have known symptomatic brain metastases requiring steroids. Participants with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and have radiographically stable disease for at least 3 months prior to study entry. Note: up to 10 mg per day of prednisone equivalent will be allowed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Cancer Center	Scottsdale	Arizona	United States	85054
2	City of Hope Cancer Center	Duarte	California	United States	91010
3	University of California, Irvine	Irvine	California	United States	92868
4	University of Southern California	Los Angeles	California	United States	90033
5	University of California, San Francisco	San Francisco	California	United States	94158
6	Mayo Cancer Center	Jacksonville	Florida	United States	32224
7	Northwestern University	Chicago	Illinois	United States	60611
8	University of Chicago Medical Center	Chicago	Illinois	United States	60637
9	Johns Hopkins University	Baltimore	Maryland	United States	21287
10	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
11	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
12	University of Michigan	Ann Arbor	Michigan	United States	48109
13	Mayo Cancer Center	Rochester	Minnesota	United States	55905
14	Washington University	Saint Louis	Missouri	United States	63110
15	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
16	Columbia University	New York	New York	United States	10032
17	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
18	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
19	Gibbs Cancer Center	Spartanburg	South Carolina	United States	29303
20	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
21	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
22	University of Texas, SouthWestern	Dallas	Texas	United States	75390
23	UT MD Anderson Cancer Center	Houston	Texas	United States	77030
24	University of Utah, Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
25	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
26	University of Wisconsin, Carbone Cancer Center	Madison	Wisconsin	United States	53792
27	Universite de Franche-Comte	Besançon		France	25000
28	Centre de Lutte Contre le Cancer (CLCC) - Institut Bergonie	Bordeaux		France	33076
29	Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer	Rennes		France	35042
30	Institut Gustave Roussy	Villejuif		France	94805
31	Fondazione del Piemonte per l'Oncologia - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS Candiolo)	Candiolo		Italy	10060
32	Istituto Scientifico Universitario San Raffaele	Milano		Italy	20127
33	Istituto Clinico Humanitas	Rozzano		Italy	20089
34	Seoul National University Hospital	Seoul		Korea, Republic of	03080
35	Yonsei University Severance Hospital	Seoul		Korea, Republic of	03722
36	Asan Medical Center	Seoul		Korea, Republic of	05505
37	Samsung Medical Center	Seoul		Korea, Republic of	06351
38	Seoul, St. Mary's Hospital	Seoul		Korea, Republic of	06591
39	National Cancer Center	Seoul		Korea, Republic of	10408
40	Hospital Vall d'Hebrón	Barcelona		Spain	08035
41	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28007
42	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
43	Centro Integral Oncologico Clara Campal	Madrid		Spain	28050
44	Hospital Universitario Marques de Valdecilla	Santander		Spain	39008
45	St. James University Hospital	Leeds		United Kingdom	LS16 6QB
46	Liverpool Cancer Center	Liverpool		United Kingdom	CH63 4JY
47	University College London Hospitals	London		United Kingdom	NW1 2PG
48	The Royal Free Hospital	London		United Kingdom	NW3 2QG
49	The Christie NHS Foundation Trust, the Christie Hospital	Manchester		United Kingdom	M20 4QL

Sponsors and Collaborators

• Agios Pharmaceuticals, Inc.

Investigators

• Study Chair: Medical Affairs Servier Pharmaceuticals LLC, Servier Pharmaceuticals, LLC

Study Documents (Full-Text)

• Study Protocol - Mar 5, 2019
• Statistical Analysis Plan - Apr 1, 2019

More Information

Publications

None provided.

• Responsible Party: Agios Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02989857
• Other Study ID Numbers: AG120-C-005
• First Posted: Dec 12, 2016
• Last Update Posted: Apr 13, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Agios Pharmaceuticals, Inc.: IDH1
• Additional relevant MeSH terms: Cholangiocarcinoma; Ivosidenib

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 49 study sites in France, Italy, Spain, South Korea, the United States, and the United Kingdom from 20 February 2017 to 17 May 2021. This is the primary results posting. The data for the primary outcome measure is reported up to 31 January 2019.
Pre-assignment Detail	The final analysis of progression-free survival (PFS) occurred once 131 PFS events had been determined by Investigator assessment. Two participants were randomized in the study after the data cutoff date (31 January 2019) for the final analysis of PFS.

Arm/Group Title	AG-120	Placebo	After Crossover to AG-120
Arm/Group Description	Participants received AG-120 500 mg, tablet, orally, once daily (QD) in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 24 months.	Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 24 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.	Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 24 months.
Period Title: Randomization Phase
STARTED	126	61	0
COMPLETED	0	0	0
NOT COMPLETED	126	61	0
Period Title: Randomization Phase
STARTED	0	0	43
COMPLETED	0	0	0
NOT COMPLETED	0	0	43

Baseline Characteristics

Arm/Group Title	AG-120	Placebo	Total
Arm/Group Description	Participants received AG-120 500 mg, tablet, orally, once daily (QD) in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 24 months.	Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 24 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.	Total of all reporting groups
Overall Participants	126	61	187
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.3 (10.97)	62.9 (10.38)	61.1 (10.82)
Sex: Female, Male (Count of Participants)
Female	82 65.1%	37 60.7%	119 63.6%
Male	44 34.9%	24 39.3%	68 36.4%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	7 5.6%	2 3.3%	9 4.8%
Not Hispanic or Latino	84 66.7%	40 65.6%	124 66.3%
Not Reported	0 0%	2 3.3%	2 1.1%
Missing	35 27.8%	17 27.9%	52 27.8%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 0.8%	0 0%	1 0.5%
Asian	15 11.9%	8 13.1%	23 12.3%
Black or African American	1 0.8%	1 1.6%	2 1.1%
Native Hawaiian or Other Pacific Islander	1 0.8%	0 0%	1 0.5%
White	71 56.3%	35 57.4%	106 56.7%
Other	1 0.8%	0 0%	1 0.5%
Not Reported	1 0.8%	0 0%	1 0.5%
Missing	35 27.8%	17 27.9%	52 27.8%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) as Determined by the Independent Radiology Committee (IRC)
Description	PFS is defined as the time from date of randomization to the date of first documented disease progression as assessed by the IRC using Response Evaluation Criteria in Solid Tumors [RECIST] v1.1, or date of death due to any cause, whichever occurred first. Disease progression was defined as greater than or equal to (≥)20 percent (%) increase in sum of the diameter of target lesions, taking as reference the smallest sum diameter recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm) or the appearance of 1 or more new lesions.
Time Frame	From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

ITT set included all participants who were randomized, with the treatment group designated according to the randomization. Number analyzed is the number of participants with data available for analyses at the specified time point. Two participants were excluded from the analysis as they were randomized in the study after the data cutoff date (31 January 2019) for the analysis of PFS.

Arm/Group Title	AG-120	Placebo
Arm/Group Description	Participants received AG-120 500 mg, tablet, orally, once daily (QD) in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 24 months.	Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 24 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.
Measure Participants	124	61
Median (95% Confidence Interval) [months]	2.7	1.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	AG-120, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-value was calculated from the one-sided stratified log-rank test.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio was calculated from stratified Cox regression model with placebo as the denominator, with two-sided 95% confidence interval.

2. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Percentage of Participants With Laboratory Abnormalities
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Percentage of Participants With Clinically Significant Vital Signs
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Eastern Cooperative Oncology Group (ECOG) Performance Status
Description	The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score classifies participants according to their functional impairment, with scores ranging from 0 to 4. ECOG PS: 0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair.
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Percentage of Participants With Concomitant Medications
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Percentage of Participants With Abnormal Electrocardiogram (ECG) Changes
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Overall Survival (OS)
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Overall Response Rate (ORR) by the Investigator
Time Frame	From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	ORR as Assessed by the IRC Per RECIST v1.1
Time Frame	From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Duration of Response (DOR) as Assessed by the Investigator
Time Frame	From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	DOR as Assessed by the IRC Per RECIST v1.1
Time Frame	From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Time to Response (TTR) as Assessed by the Investigator
Time Frame	From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	TTR as Assessed by the IRC Per RECIST v1.1
Time Frame	From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Secondary Outcome

Title	PFS Per Investigator Assessment
Time Frame	From the date of randomization to the date of first documentation of disease progression or death due to any cause (Up to approximately 2 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

16. Secondary Outcome

Title	Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30
Description	The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single-item assessments (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. Most of the 30 items have 4 response levels (not at all, a little, quite a bit, and very much). Raw scores are converted into scale scores ranging from 0 to 100. For C30-Overall Health and C30-Quality of Life, higher scores indicate better condition.
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Secondary Outcome

Title	HRQOL: Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21)
Description	The QLQ-BIL21 contains 21 items in total and each item is a 4-point Likert scale. These 21 items can be grouped into 5 scales (eating symptoms, jaundice symptoms, tiredness, pain symptoms, and anxiety symptoms) and 3 single-item assessments (treatment side-effects, difficulties with drainage bag/tubes, and concerns regarding weight loss). Most of the 21 items have 4 response levels (not at all, a little, quite a bit, and very much). Higher scores indicate better condition.
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

18. Secondary Outcome

Title	HRQOL: Patient Global Impression of Change (PGI-C)
Description	The anchor-based questionnaire PGI-C contains the following 3 items (the overall change in the physical functioning since the start of taking the study medication, the overall change in the appetite since the start of taking the study medication, and the overall change in the pain since the start of taking the study medication). The PGI-C is measured using a 7-point Likert scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse.
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

19. Secondary Outcome

Title	HRQOL: Patient Global Impression of Severity (PGI-S)
Description	The anchor-based questionnaire PGI-S contains the following 3 items (the severity of the physical functioning decline over the past week, the severity of the appetite decrease over the past week, and the severity of the pain over the past week). The PGI-S is measured using a 7-point Likert scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse.
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

20. Secondary Outcome

Title	Health Economic Outcomes: 5-level EuroQol Five Dimensions Questionnaire (EQ-5D-5L)
Description	The EQ-5D-5L contains 5 dimensions (Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression) as well as the EQ visual analogue scale (VAS). EQ-5D-5L consists of 2 components: a descriptive system of the participant's health and a rating of his or her current health state on a 0-100 VAS. The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health.
Time Frame	Up to approximately 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

21. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of AG-120
Time Frame	Day 1 of every cycle up to End of Treatment (EOT) (up to approximately 4 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

22. Secondary Outcome

Title	Time to Reach Maximal Plasma Concentration (Tmax) of AG-120
Time Frame	Day 1 of every cycle up to EOT (up to approximately 4 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

23. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours (AUC0-4)
Time Frame	Day 1 of every cycle up to EOT (up to approximately 4 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

24. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24)
Time Frame	Day 1 of every cycle up to EOT (up to approximately 4 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

25. Secondary Outcome

Title	Accumulation Ratio Based on AUC0-4 (Racc AUC0-4)
Time Frame	Day 1 of every cycle up to EOT (up to approximately 4 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

26. Secondary Outcome

Title	Accumulation Ratio Based on Cmax (Racc Cmax)
Time Frame	Day 1 of every cycle up to EOT (up to approximately 4 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

27. Secondary Outcome

Title	Plasma 2-hydroxyglutarate (2-HG) Levels of AG-120
Time Frame	Day 1 of every cycle up to EOT (up to approximately 4 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From first dose of study drug up to 28 days after last dose (Up to approximately 24 months)
Adverse Event Reporting Description	Safety Analysis Set included all participants who received at least one dose of study treatment.
Arm/Group Title	AG-120		Placebo		After Cross Over to AG-120
Arm/Group Description	Participants received AG-120 500 mg, tablet, orally, once daily (QD) in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up, or the sponsor ended the study for up to approximately 24 months.		Participants received AG-120 matched placebo, orally, QD in each 28-day treatment cycle, until occurrence of disease progression, unacceptable toxicity, confirmed pregnancy, death, subject withdrawal, lost to follow-up or the sponsor ended the study for up to approximately 24 months. Participants who experienced disease progression and received placebo were allowed to cross over and receive AG-120.		Participants who experienced disease progression and received placebo were allowed to cross over to receive AG-120 500 mg, tablet, orally, QD in each 28-day treatment cycle for up to approximately 24 months.
All Cause Mortality
	AG-120		Placebo		After Cross Over to AG-120
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/123 (80.5%)		14/59 (23.7%)		34/43 (79.1%)
Serious Adverse Events
	AG-120		Placebo		After Cross Over to AG-120
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/123 (35%)		14/59 (23.7%)		12/43 (27.9%)
Blood and lymphatic system disorders
Anaemia	1/123 (0.8%)		0/59 (0%)		1/43 (2.3%)
Blood loss anaemia	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Cardiac disorders
Tachyarrhythmia	0/123 (0%)		1/59 (1.7%)		0/43 (0%)
Ear and labyrinth disorders
Vertigo	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Gastrointestinal disorders
Abdominal distension	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Abdominal pain	1/123 (0.8%)		1/59 (1.7%)		0/43 (0%)
Abdominal pain lower	0/123 (0%)		1/59 (1.7%)		0/43 (0%)
Ascites	3/123 (2.4%)		2/59 (3.4%)		1/43 (2.3%)
Dysphagia	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Gastrointestinal haemorrhage	1/123 (0.8%)		0/59 (0%)		1/43 (2.3%)
Intestinal obstruction	2/123 (1.6%)		0/59 (0%)		0/43 (0%)
Intestinal pseudo-obstruction	0/123 (0%)		0/59 (0%)		1/43 (2.3%)
Large intestinal obstruction	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Nausea	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Oesophageal varices haemorrhage	0/123 (0%)		0/59 (0%)		1/43 (2.3%)
Upper gastrointestinal haemorrhage	1/123 (0.8%)		0/59 (0%)		1/43 (2.3%)
Vomiting	2/123 (1.6%)		0/59 (0%)		1/43 (2.3%)
General disorders
Asthenia	0/123 (0%)		1/59 (1.7%)		0/43 (0%)
Non-cardiac chest pain	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Pain	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Pyrexia	2/123 (1.6%)		0/59 (0%)		1/43 (2.3%)
Localised oedema	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Hepatobiliary disorders
Biliary obstruction	1/123 (0.8%)		0/59 (0%)		1/43 (2.3%)
Bile duct stenosis	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Cholangitis	3/123 (2.4%)		0/59 (0%)		1/43 (2.3%)
Cholangitis acute	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Cholecystitis	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Hepatic cirrhosis	0/123 (0%)		0/59 (0%)		1/43 (2.3%)
Hepatic failure	1/123 (0.8%)		1/59 (1.7%)		0/43 (0%)
Hepatic haemorrhage	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Hyperbilirubinaemia	3/123 (2.4%)		0/59 (0%)		0/43 (0%)
Jaundice	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Jaundice cholestatic	3/123 (2.4%)		0/59 (0%)		0/43 (0%)
Infections and infestations
Abdominal infection	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Bacteraemia	0/123 (0%)		0/59 (0%)		1/43 (2.3%)
Bacterial infection	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Biliary sepsis	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Biliary tract infection	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Clostridium difficile colitis	0/123 (0%)		0/59 (0%)		1/43 (2.3%)
Device related infection	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Escherichia bacteraemia	2/123 (1.6%)		0/59 (0%)		1/43 (2.3%)
Gastroenteritis	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Parainfluenzae virus infection	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Pneumonia	4/123 (3.3%)		1/59 (1.7%)		0/43 (0%)
Sepsis	4/123 (3.3%)		2/59 (3.4%)		0/43 (0%)
Staphylococcal infection	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Systemic candida	0/123 (0%)		1/59 (1.7%)		0/43 (0%)
Wound infection	0/123 (0%)		1/59 (1.7%)		0/43 (0%)
Injury, poisoning and procedural complications
Arterial injury	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Fall	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Hip fracture	2/123 (1.6%)		0/59 (0%)		1/43 (2.3%)
Investigations
Aspartate aminotransferase increased	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Blood bilirubin increased	2/123 (1.6%)		0/59 (0%)		1/43 (2.3%)
Electrocardiogram QT prolonged	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Gamma-glutamyltransferase increased	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Metabolism and nutrition disorders
Dehydration	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Failure to thrive	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Hypercalcaemia	1/123 (0.8%)		2/59 (3.4%)		1/43 (2.3%)
Hyperkalaemia	1/123 (0.8%)		2/59 (3.4%)		0/43 (0%)
Hypokalaemia	0/123 (0%)		1/59 (1.7%)		0/43 (0%)
Hyponatraemia	1/123 (0.8%)		1/59 (1.7%)		0/43 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/123 (0%)		2/59 (3.4%)		1/43 (2.3%)
Nervous system disorders
Cognitive disorder	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Depressed level of consciousness	0/123 (0%)		1/59 (1.7%)		0/43 (0%)
Encephalopathy	0/123 (0%)		0/59 (0%)		1/43 (2.3%)
Hepatic encephalopathy	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Multiple sclerosis relapse	0/123 (0%)		0/59 (0%)		1/43 (2.3%)
Spinal cord compression	0/123 (0%)		0/59 (0%)		1/43 (2.3%)
Syncope	0/123 (0%)		0/59 (0%)		1/43 (2.3%)
Thecal sac compression	0/123 (0%)		1/59 (1.7%)		0/43 (0%)
Psychiatric disorders
Confusional state	1/123 (0.8%)		1/59 (1.7%)		0/43 (0%)
Mental status changes	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Renal and urinary disorders
Acute kidney injury	0/123 (0%)		0/59 (0%)		1/43 (2.3%)
Nephropathy toxic	0/123 (0%)		1/59 (1.7%)		0/43 (0%)
Renal failure	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/123 (0.8%)		1/59 (1.7%)		0/43 (0%)
Pleural effusion	2/123 (1.6%)		0/59 (0%)		0/43 (0%)
Pulmonary embolism	1/123 (0.8%)		0/59 (0%)		0/43 (0%)
Vascular disorders
Hypotension	0/123 (0%)		1/59 (1.7%)		1/43 (2.3%)
Other (Not Including Serious) Adverse Events
	AG-120		Placebo		After Cross Over to AG-120
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	118/123 (95.9%)		56/59 (94.9%)		36/43 (83.7%)
Blood and lymphatic system disorders
Anaemia	23/123 (18.7%)		3/59 (5.1%)		7/43 (16.3%)
Gastrointestinal disorders
Nausea	52/123 (42.3%)		17/59 (28.8%)		12/43 (27.9%)
Diarrhoea	43/123 (35%)		10/59 (16.9%)		12/43 (27.9%)
Abdominal pain	30/123 (24.4%)		9/59 (15.3%)		7/43 (16.3%)
Ascites	25/123 (20.3%)		7/59 (11.9%)		5/43 (11.6%)
Vomiting	28/123 (22.8%)		11/59 (18.6%)		5/43 (11.6%)
Constipation	20/123 (16.3%)		11/59 (18.6%)		5/43 (11.6%)
Abdominal distension	13/123 (10.6%)		5/59 (8.5%)		2/43 (4.7%)
Abdominal pain upper	10/123 (8.1%)		2/59 (3.4%)		4/43 (9.3%)
Gastrooesophageal reflux disease	9/123 (7.3%)		2/59 (3.4%)		1/43 (2.3%)
Dyspepsia	7/123 (5.7%)		3/59 (5.1%)		1/43 (2.3%)
Abdominal discomfort	4/123 (3.3%)		0/59 (0%)		3/43 (7%)
Dry mouth	3/123 (2.4%)		4/59 (6.8%)		1/43 (2.3%)
General disorders
Fatigue	38/123 (30.9%)		10/59 (16.9%)		10/43 (23.3%)
Oedema peripheral	17/123 (13.8%)		6/59 (10.2%)		9/43 (20.9%)
Asthenia	17/123 (13.8%)		7/59 (11.9%)		5/43 (11.6%)
Pyrexia	16/123 (13%)		6/59 (10.2%)		2/43 (4.7%)
Chills	8/123 (6.5%)		3/59 (5.1%)		1/43 (2.3%)
Gait disturbance	0/123 (0%)		3/59 (5.1%)		0/43 (0%)
Infections and infestations
Urinary tract infection	7/123 (5.7%)		1/59 (1.7%)		1/43 (2.3%)
Upper respiratory tract infection	4/123 (3.3%)		0/59 (0%)		3/43 (7%)
Investigations
Aspartate aminotransferase increased	13/123 (10.6%)		3/59 (5.1%)		3/43 (7%)
Blood alkaline phosphatase increased	11/123 (8.9%)		6/59 (10.2%)		4/43 (9.3%)
Blood bilirubin increased	12/123 (9.8%)		4/59 (6.8%)		2/43 (4.7%)
Weight decreased	10/123 (8.1%)		3/59 (5.1%)		6/43 (14%)
Alanine aminotransferase increased	11/123 (8.9%)		1/59 (1.7%)		3/43 (7%)
Electrocardiogram QT prolonged	11/123 (8.9%)		2/59 (3.4%)		1/43 (2.3%)
White blood cell count decreased	9/123 (7.3%)		1/59 (1.7%)		2/43 (4.7%)
Blood creatinine increased	7/123 (5.7%)		3/59 (5.1%)		1/43 (2.3%)
Platelet count decreased	7/123 (5.7%)		3/59 (5.1%)		2/43 (4.7%)
Metabolism and nutrition disorders
Decreased appetite	30/123 (24.4%)		11/59 (18.6%)		6/43 (14%)
Hyponatraemia	14/123 (11.4%)		6/59 (10.2%)		1/43 (2.3%)
Hypokalaemia	10/123 (8.1%)		4/59 (6.8%)		2/43 (4.7%)
Hypoalbuminaemia	8/123 (6.5%)		4/59 (6.8%)		3/43 (7%)
Hyperglycaemia	9/123 (7.3%)		1/59 (1.7%)		2/43 (4.7%)
Hypomagnesaemia	9/123 (7.3%)		3/59 (5.1%)		1/43 (2.3%)
Hypophosphataemia	6/123 (4.9%)		3/59 (5.1%)		3/43 (7%)
Hyperkalaemia	6/123 (4.9%)		3/59 (5.1%)		2/43 (4.7%)
Hypercalcaemia	2/123 (1.6%)		7/59 (11.9%)		1/43 (2.3%)
Musculoskeletal and connective tissue disorders
Back pain	16/123 (13%)		7/59 (11.9%)		2/43 (4.7%)
Arthralgia	14/123 (11.4%)		6/59 (10.2%)		5/43 (11.6%)
Muscle spasms	6/123 (4.9%)		1/59 (1.7%)		4/43 (9.3%)
Muscular weakness	1/123 (0.8%)		2/59 (3.4%)		4/43 (9.3%)
Nervous system disorders
Headache	16/123 (13%)		4/59 (6.8%)		2/43 (4.7%)
Dizziness	7/123 (5.7%)		1/59 (1.7%)		4/43 (9.3%)
Neuropathy peripheral	8/123 (6.5%)		0/59 (0%)		0/43 (0%)
Psychiatric disorders
Insomnia	12/123 (9.8%)		3/59 (5.1%)		3/43 (7%)
Confusional state	4/123 (3.3%)		3/59 (5.1%)		2/43 (4.7%)
Respiratory, thoracic and mediastinal disorders
Cough	31/123 (25.2%)		5/59 (8.5%)		5/43 (11.6%)
Dyspnoea	12/123 (9.8%)		10/59 (16.9%)		4/43 (9.3%)
Skin and subcutaneous tissue disorders
Rash	10/123 (8.1%)		0/59 (0%)		2/43 (4.7%)
Pruritus	7/123 (5.7%)		3/59 (5.1%)		3/43 (7%)
Rash maculo-papular	4/123 (3.3%)		3/59 (5.1%)		1/43 (2.3%)
Vascular disorders
Hypertension	11/123 (8.9%)		2/59 (3.4%)		4/43 (9.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The information obtained from the clinical study will be used towards the development of ivosidenib and may be disclosed to regulatory authority(ies), other Investigators, corporate partners, or consultants as required.