TIBSOVO^® DELIVERED IMPROVED OUTCOMES IN CHOLANGIOCARCINOMA (CCA)

ClarIDHy was a large, global, randomized phase 3 trial and the first to demonstrate clinical benefit with targeted therapy in advanced mIDH1 CCA^1,2

The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival, objective response rate, safety, and quality of life.^2,3

TIBSOVO was studied in a phase 3, randomized, double-blind, placebo-controlled, multicenter trial in a CCA patient population reflective of that seen in clinical practice.^2,3

ClarIDHy study design

TIBSOVO^® was studied in a patient population reflective of that seen in a clinical practice³

Selected baseline demographics and disease characteristics (N=185)¹

		TIBSOVO (n=124)	Placebo (n=61)
Demographics
Median age, years (min, max)		61 (33, 80)	63 (40, 83)
Sex
Male		36%	40%
Female		65%	61%
Race
White		57%	57%
Asian		12%	13%
Black		0.8%	1.6%
Native Hawaiian/Other Pacific Islander		0.8%	0%
American Indian or Alaska Native		0.8%	0%
Disease characteristics
Prior lines of therapy
1 prior line of therapy		53%	54%
2 prior lines of therapy		47%	46%
ECOG PS
0		40%	31%
1		60%	67%
IDH1 mutation
R132C		68%	74%
R132L		17%	12%
R132G		14%	10%
R132H		0%	3.3%
R132S		1.6%	1.6%
Cholangiocarcinoma type at initial diagnosis
Intrahepatic		90%	95%
Metastatic disease		93%	92%

ECOG PS, Eastern Cooperative Oncology Group Performance Status.

Baseline characteristics

TIBSOVO^® (ivosidenib tablets) was studied in a phase 3, randomized, double-blind, placebo-controlled, multicenter trial—one of the largest clinical trials to date of a targeted therapy in cholangiocarcinoma^1-3

CCA, cholangiocarcinoma; ECOG PS, Eastern Cooperative Oncology Group Performance Status; IDH1, isocitrate dehydrogenase-1; mIDH1, mutated IDH1; NGS, next-generation sequencing; QD, once a day; RECIST, Response Evaluation Criteria in Solid Tumors.

Recommendation from the NCCN Clinical Practice Guidelines in Oncology
(NCCN Guidelines^®)

Ivosidenib (TIBSOVO) is recommended as an NCCN category 1 subsequent-line systemic treatment option for patients with unresectable or metastatic progressive CCA with IDH1 mutations.^4,a

^aTo view the most recent and complete version of the guidelines, visit NCCN.org.

mIDH1, mutated isocitrate dehydrogenase-1; NCCN, National Comprehensive Cancer Network^® (NCCN^®).

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TIBSOVO delivered significant improvements in PFS¹

PFS for TIBSOVO vs placebo^1,3

CI, confidence interval; HR, hazard ratio.

^bPatients 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.²

• 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

Treatment duration within ClarIDHy trial

Treatment duration for all patients treated with TIBSOVO²

Description

Swimmer plot presenting treatment duration for all patients treated with TIBSOVO in previously treated IDH1-mutated cholangiocarcinoma. The x-axis spans from 0 to 36 months of treatment duration. Each patient is represented individually, with ongoing patients indicated by a separate marker. 15% of patients remained on TIBSOVO for over a year.

^cOngoing as of data cutoff (May 31, 2020).

Treatment duration for all patients treated with placebo, including those who crossed over to TIBSOVO²

Description

Swimmer plot presenting treatment duration for all patients treated with placebo, including those who crossed over to TIBSOVO, in previously treated IDH1-mutated cholangiocarcinoma. The x-axis spans from 0 to 36 months of treatment duration. Each patient is represented individually, with placebo duration shown in gray and TIBSOVO duration following crossover shown in blue. Ongoing patients are indicated by a separate marker.

^cOngoing as of data cutoff (May 31, 2020).

Overall survival (OS) data with TIBSOVO

OS for TIBSOVO vs placebo (intent-to-treat set)^2,d

CI, confidence interval; HR, hazard ratio.

^dOS results are based on the final analysis of OS (based on 150 deaths), which occurred 16 months after the final analysis of PFS.¹

^ePatients 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

^fThis prespecified model, known as RPSFT, is one of the most commonly used statistical methods to adjust for treatment switching in oncology trials. This sensitivity analysis was exploratory, and appropriate multiplicity adjustments were not applied.

^gThe RPSFT model is based on the assumption that the treatment effect of TIBSOVO is the same for all individuals, regardless of when treatment is received. This assumption was not verified.

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 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).

Health-related quality of life (QoL)

• CCA is associated with an impaired QoL, a metric that is increasingly regarded as a crucial endpoint in clinical trials⁵
• Health-related QoL was assessed using two tools; the EORTC QLQ-C30, a generic cancer questionnaire, and the EORTC QLQ-BIL21, a disease-specific module²
• TIBSOVO was favored on physical functioning, as well as subscales such as pain, emotional functioning, cognitive functioning, dyspnea, anxiety, and tiredness²
• Analyses of the QoL data were limited by small sample sizes.² Assessments depicted were at Cycle 2 Day 1^2,i

EORTC QLQ-C30 global health status/QoL and functional subscales⁶

Higher scores indicate a favorable outcome.

EORTC QLQ-C30 symptoms subscales⁶

Lower scores indicate a favorable outcome.

EORTC QLQ-BIL21 subscales⁶

Lower scores indicate a favorable outcome.

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.

CI, confidence interval; EORTC QLQ-BIL21, EORTC QLQ cholangiocarcinoma and gallbladder cancer module; EORTC QLC-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; LS, least squares.

ⁱAt 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).²