Ivosidenib Shows Clinical Benefit in IDH1-Mutant Advanced Cholangiocarcinoma

At the 2019 ESMO Congress, Ghassan Abou-Alfa, MD, MBA, Medical Oncologist, Memorial Sloan Kettering Cancer Center, New York, NY, discusses the results from the ClarIDHy trial, which show the potential for ivosidenib as a new standard for patients with IDH1-mutant advanced cholangiocarcinoma.

Transcript

We're very honored and happy to be here in Barcelona for ESMO 2019, where, on behalf of all co-authors, I presented the data on ClarIDHy, a phase 3 clinical trial of ivosidenib versus placebo in patients with advanced cholangiocarcinoma and mutated IDH1.

Mutated IDH1 will cause alpha-ketoglutarate to get used to 2-hydroxyglutarate, which is an oncometabolite. In a phase 1 clinical trial, we were able to find in a cohort of patients with cholangiocarcinoma a progression-free survival of about 3.8 months and median survival of about 13.8 months.

This collection of data led to the ClarIDHy study, which was a randomized trial for ivosidenib versus placebo. Patients on this study, if they were on the placebo arm that was randomized 2:1, they were allowed to cross over to the ivosidenib arm if there was evident progression of disease radiologically.

The trial reported a primary end point that progression-free survival is positive, with 2.4-months median progression-free survival for the ivosidenib arm, versus 1.4 months for the placebo. Importantly, though, the suppression of the curve for the progression-free survival was apparent, of course, at the time of the first CAT scan, 1.5 months into the study.

In addition to that, the separation of the curves continued beyond the median, with 6 months progression-free survival for the ivosidenib arm, 32%, and not evaluable or estimable for the placebo arm, because there were no patients there.

The 12-month progression-free survival rate was 22% again for ivosidenib, and not evaluable for the placebo arm, because there were no patients there. The hazard ratio was 0.38, with EP values at 0.001.

In regard to the overall survival, it again favored the ivosidenib, 10.8 months, versus 9.8 months for the placebo. However, in view of the crossover, an RPSFD method was used to recalculate the placebo arm survival to accommodate for as if the patient did not really cross over, per se.

This reduced the survival of the placebo patients arm to a 6 months. Now, we're comparing 10.8 months versus 6 months, again, with hazard ratio of 0.47 and p-value less than 0.001. The drug was rather well-tolerated.

The most common side effects were nausea, fatigue, and diarrhea. The quality of life showed an improvement in favor of the ivosidenib and this was for physical activity, as well as emotional support.

As such, we can say that ivosidenib shows in the ClarIDHy study that it could have an improvement in progression-free survival in patients with metastatic cholangiocarcinoma with mutated IDH1. In addition to that, shows the improvement in overall survival with a trend to grow positive that even improved further with the RPSFD method for analysis, with, again, a hazard ratio of 0.47 and a p-value less than 0.001.

The drug was well-tolerated, and we're happy to see it as a potential standard for patients with mutated IDH1 and advanced cholangiocarcinoma.