FDA approval of Tibsovo to treat AML is based on Study AG120-C-001, NCT02074839.- Agios Pharma.

The FDA approval for Tibsovo (ivosidenib) was based on the clinical data from an open-label, single-arm, multicenter dose-escalation and expansion trial of adult patients with R/R AML and an IDH1 mutation (Study AG120-C-001, NCT02074839). Tibsovo was approved concurrently with the Abbott RealTime IDH1 companion diagnostic test for selection of patients with R/R AML for treatment with Tibsovo

The efficacy of Tibsovo was evaluated in 174 adult patients with R/R AML with an IDH1 mutation identified or confirmed by the Abbott RealTime IDH1 assay. Tibsovo was given orally at a starting dose of 500 mg daily until disease progression, development of unacceptable toxicity, or undergoing hematopoietic stem cell transplantation. Patients had a median age of 67 years (range of 18 to 87) and received a median of two prior anticancer therapies (ranging from one to six). More than half (63%) were refractory to previous therapy and 33% had secondary AML. The primary endpoint is the combined complete remission (CR) and complete remission with partial hematologic improvement (CRh) rate. CRh is defined as <5% of blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter).

In this trial, Tibsovo demonstrated: CR+CRh rate of 32.8% (57 of 174 patients) (95% CI: 25.8, 40.3). The CR rate was 24.7% (43 of 174 patients) (95% CI 18.5, 31.8) and the CRh rate was 8% (14 of 174 patients) (95% CI 4.5, 13.1). Median duration of CR+CRh was 8.2 months (95% CI: range 5.6, 12 months). For patients who achieved a CR or CRh, the median time to best response of CR or CRh was 2.0 months (range, 0.9 to 5.6 months). Among the 110 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 41 (37.3%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of the 64 patients who were independent of both RBC and platelet transfusions at baseline, 38 (59.4%) remained transfusion independent during any 56-day post-baseline period. Twenty-one of the 174 patients (12%) went on to stem cell transplant following Tibsovo treatment.

The safety profile of single-agent Tibsovo was evaluated in 179 patients with R/R AML with an IDH1 mutation treated with a dose of 500 mg daily. The median duration of exposure to Tibsovo was 3.9 months (range 0.1 to 39.5 months). In the clinical trial, 19% (34/179) of patients treated with Tibsovo experienced differentiation syndrome, which can be fatal if not treated. QTc interval prolongation and Guillain-Barré Syndrome occurred in patients treated with Tibsovo. The most common adverse reactions (?20%) of any grade were fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, electrocardiogram QT prolonged, rash, pyrexia, cough and constipation. The most frequent serious adverse reactions (?5%) were differentiation syndrome (10%), leukocytosis (10%) and electrocardiogram QT prolonged (7%).