Data from phase III ClarIDHy trial of Tibsovo demonstrates significant improvement in progression free survival in previously treated IDH1 mutant cholangiocarcinoma patients. Agios Pharma

Agios Pharmaceuticals, Inc. presented data from the global Phase III ClarIDHy trial of Tibsovo (ivosidenib) in previously treated cholangiocarcinoma patients with an isocitrate dehydrogenase 1 (IDH1) mutation in a Presidential Symposium at the European Society for Medical Oncology Congress (ESMO). Results from the ClarIDHy trial demonstrated a statistically significant improvement in progression-free survival (PFS) by independent radiology review of 2.7 months among patients randomized to Tibsovo compared with 1.4 months among placebo patients (hazard ratio [HR] 0.37; 95% CI [0.25, 0.54], p<0.001). the safety profile observed in the study was consistent with previously published data.>

�Advanced cholangiocarcinoma is an aggressive disease oftentimes characterized by rapid progression following multiple lines of therapy, and there are no currently approved treatments,� said Ghassan Abou-Alfa, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center, who presented the data at ESMO. �The ClarIDHy study is the first randomized trial in previously treated IDH1 mutant cholangiocarcinoma patients and demonstrates that Tibsovo provides significant improvement in PFS compared to placebo, while also showing a favorable trend in overall survival. These critical data also provide strong justification for genomic testing in cholangiocarcinoma patients where a targeted therapeutic approach may provide benefit.�

ClarIDHy Phase III Trial : The ClarIDHy trial is a global, randomized Phase III trial in previously treated IDH1 mutant cholangiocarcinoma patients who have documented disease progression following one or two systemic therapies in the advanced setting. Patients were randomized 2:1 to receive either single-agent Tibsovo 500 mg once daily or placebo with crossover to Tibsovo permitted at the time of documented radiographic progression per RECIST 1.1. As of the January 31, 2019 data cutoff, 185 patients were randomized, with 124 patients in the Tibsovo arm and 61 patients in the placebo arm. Thirty-five patients randomized to placebo (57.4%) crossed over to open-label Tibsovo upon radiographic disease progression and unblinding.

Efficacy Results: Efficacy data as of the data cut-off showed: Median progression-free survival (PFS) for patients randomized to Tibsovo was 2.7 months compared to 1.4 months with placebo (hazard ratio [HR]=0.37; 95% CI [0.25, 0.54], p<0.001) as assessed by independent radiology review. pfs benefits were observed across all subgroups analyzed. the estimated pfs rate was 32% at six months and 22% at 12 months for patients randomized to tibsovo, while no patients randomized to placebo were free from progression beyond these timepoints as of the data cut-off. in the tibsovo arm, 2% of patients achieved a partial response and 51% had stable disease, compared to 28% with stable disease in the placebo arm. median overall survival (os) based on 78 events was 10.8 months for patients randomized to tibsovo compared to 9.7 months for placebo patients (hr="0.69;" 95% ci [0.44, 1.10], p="0.06)." using the rank-preserving structural failure time (rpsft) method to reconstruct the survival curve for the placebo subjects as if they never crossed over to tibsovo, the median os with placebo adjusts to 6 months (hr="0.46;" 95% ci [0.28, 0.75], p><0.001).>

Safety Results :A safety analysis conducted for all patients as of the data cut-off demonstrated: Less than half of patients experienced a Grade 3 or above treatment-emergent adverse event (TEAE) in either arm (46.2% with total Tibsovo [includes patients who crossed over from placebo to Tibsovo] vs. 35.6% on placebo), with the most common being ascites (7.7% total Tibsovo vs. 6.8% placebo). TEAEs leading to discontinuation were more common with placebo compared with total Tibsovo� (8.5% vs. 5.8%). TEAEs leading to dose reductions (2.6% vs. 0%) and interruptions (26.3% vs. 16.9%) were more common with total Tibsovo relative to placebo. The most common TEAEs of any grade for total Tibsovo were nausea (32%), diarrhea (29%) and fatigue (24%).