Phase I Trial of a Tablet Formulation of Pilaralisib, a Pan‐Class I PI3K Inhibitor, in Patients with Advanced Solid Tumors

LESSONS LEARNED. A phase I study of the pan‐class I phosphoinositide 3‐kinase inhibitor pilaralisib (in capsule formulation) in advanced solid tumors established the maximum tolerated dose as 600 mg once daily. The current study investigated pilaralisib in tablet formulation. Pilaralisib tablets were associated with a favorable safety profile and preliminary antitumor activity. Based on pharmacokinetic data, the recommended phase II dose of pilaralisib tablets was established as 400 mg once daily. BACKGROUND. A phase I trial of pilaralisib, an oral pan‐class I phosphoinositide 3‐kinase (PI3K) inhibitor, established the maximum tolerated dose (MTD) of the capsule formulation in patients with advanced solid tumors as 600 mg once daily. This phase I study investigated pilaralisib in tablet formulation. MATERIALS AND METHODS. Patients with advanced solid tumors received pilaralisib tablets (100–600 mg once daily). Primary endpoints were MTD and safety; secondary and exploratory endpoints included pharmacokinetics (PK), pharmacodynamics, and efficacy. RESULTS. Twenty‐two patients were enrolled. No dose‐limiting toxicities (DLTs) were reported. The most common treatment‐related adverse events were diarrhea (40.9%), fatigue (40.9%), decreased appetite (22.7%), and hyperglycemia (22.7%). Pilaralisib plasma exposure did not appear to increase dose‐proportionally. Steady‐state exposure was higher with pilaralisib tablet formulation at 400 mg than with pilaralisib capsule formulation at 400 or 600 mg (mean area under the curve [AUC(0–24)] 2,820,000 ng × h/mL vs. 2,653,000 and 1,930,000 ng × h/mL, respectively). Of 18 evaluable patients, 2 (11.1%) had a partial response (PR). CONCLUSION. Pilaralisib tablets were associated with a favorable safety profile and preliminary antitumor activity. MTD was not determined. The recommended phase II dose for pilaralisib tablets, based on PK data, was 400 mg once daily.