The ClarIDHy trial for TIBSOVO® (ivosidenib tablets) was the first phase 3 trial to show clinical benefit with targeted therapy in mIDH1 cholangiocarcinoma2
(500 mg DAILY)
|Progression-free survival by IRC assessment||n=124||n=61|
|Events, n (%)||76 (61)||50 (82)|
|Progressive disease||64 (52)||44 (72)|
|Death||12 (10)||6 (10)|
|Hazard ratio (95% CI)a||0.37 (0.25, 0.54)|
|Objective response rate, n (%)||3 (2.4)||0|
|Deaths, n (%)||100 (79)||50 (82)|
|Hazard ratio (95% CI)a||0.79 (0.56, 1.12)|
CI, confidence interval; IRC, independent review committee; mIDH1, mutated isocitrate dehydrogenase-1.
aHazard ratios were calculated from stratified Cox regression model. Stratification factor is the number of prior lines of therapy.
bP values were calculated from the one-sided stratified log-rank test. Stratification factor is the number of prior lines of therapy.
cOverall survival (OS) results were based on the final analysis of OS (based on 150 deaths), which occurred 16 months after the final analysis of progression-free survival. The median OS (95% CI) for TIBSOVO was 10.3 (7.8, 12.4) months and placebo was 7.5 (4.8, 11.1) months without adjusting for crossover. In the analysis of OS, 70% of the patients randomized to placebo had crossed over to receive TIBSOVO after radiographic disease progression.
Primary endpoint: progression-free survival (PFS)
TIBSOVO delivered significant improvements in PFS1,3
PFS for TIBSOVO vs placebo1,3
CI, confidence interval; HR, hazard ratio.
dPatients were censored if they were missing a baseline assessment, missing documented progression or death before data cutoff, started alternate anticancer systemic treatment, or had documented progression or death following 95 days or more from the previous adequate assessment.3
- 63% reduction in the risk of disease progression or death (HR, 0.37 [95% CI, 0.25-0.54]; P<0.0001)1
- Nearly 1 in 4 patients receiving TIBSOVO remained progression free at 12 months3
- None of the patients assigned to placebo had PFS of 6 months or greater3
- The median PFS was nearly twice as long for patients assigned to TIBSOVO compared with placebo (2.7 months [95% CI, 1.6-4.2] versus 1.4 months [95% CI, 1.4-1.6])3
- 15% of patients remained on TIBSOVO for over a year2
MEDIAN TREATMENT DURATION
(range, 0.1 to 34.4 months)
(range, 0 to 6.9 months)
5X longer maximum treatment duration with TIBSOVO vs placebo2
Treatment duration for all patients treated with TIBSOVO2
eOngoing as of data cutoff (May 31, 2020).
Secondary endpoint: overall survival (OS)
OS for TIBSOVO vs placebo (intent-to-treat set)2,f
|Number of events (%)||100 (79.4)||50 (82.0)|
|Median OS, months||10.3||7.5|
|12-month rate||43% (95% CI, 34%-51%)||36% (95% CI, 24%-48%)|
CI, confidence interval; HR, hazard ratio.
fOS results are based on the final analysis of OS (based on 150 deaths), which occurred 16 months after the final analysis of PFS.1
gPatients without documentation of death at the time of the data cutoff for analysis were censored at the date the subject was last known to be alive or the data cutoff date, whichever was earlier.2
Secondary endpoint: disease control
More than half (51%) of patients receiving TIBSOVO achieved stable disease3
ORR, objective response rate; SD, stable disease.
hThe disease control rate (ORR + SD) was due mostly to the SD rate (an ORR rate of 2% [3 partial responses] and an SD rate of 51% with TIBSOVO vs an ORR of 0% and an SD rate of 28% with placebo).
Secondary endpoint: health-related quality of life (QoL)
- Health-related quality of life was assessed using EORTC QLQ-C30 and EORTC QLQ-BIL21.3 These tools were not validated specifically in advanced CCA
- Trial protocol was designed to assess the statistical differences between the 2 treatment arms and the clinically meaningful change within arms3
- Analyses of the QoL data were limited by small sample sizes. Assessments depicted were at Cycle 2 Day 14,i
EORTC QLC-C30 global health status/QoL and functional subscales4
EORTC QLQ-C30 symptoms subscales4
These QoL analyses were exploratory, and appropriate multiplicity adjustments were not applied. Results of these individual components need cautious interpretation and could represent chance findings.
CCA, cholangiocarcinoma; CI, confidence interval; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; EORTC QLQ-BIL21, EORTC QLQ cholangiocarcinoma and gallbladder cancer module; LS, least squares.
i At baseline: n=53 for placebo and n=114 for TIBSOVO (QLQ-c30); n=52 for placebo and n=108 for TIBSOVO (QLQ-BIL21). At Cycle 2 Day 1: n=24 for placebo and n=68 for TIBSOVO (QLQ-C30); n=23 for placebo and n=68 for TIBSOVO (QLQ-BIL21). At Cycle 3 Day 1: n=12 for placebo and n=52 for TIBSOVO (QLQ-C30); n=12 for placebo and n=52 for TIBSOVO (QLQ-BIL21).4
TIBSOVO was studied in a patient population reflective of that seen in clinical practice
Selected baseline demographics and disease characteristics (N=185)1
|Median age, years (min, max)||62 (33, 83)|
|Native Hawaiian/Other Pacific Islander||0.5%|
|American Indian or Alaska Native||0.5%|
|Prior lines of therapy|
|≥1 prior lines of therapy||100%|
|2 prior lines of therapy||47%|
|Cholangiocarcinoma type at initial diagnosis|
ECOG PS, Eastern Cooperative Oncology Group Performance Status.
Patient demographics and baseline disease characteristics were well balanced between treatment arms.3