The purpose of this first-in-human (FIH) study of BLZ945 given as a single agent or in
combination with PDR001 was to characterize the safety, tolerability, pharmacokinetics
(PK), pharmacodynamics, and anti-tumor activity of BLZ945, administered orally, as a
single agent or in combination with PDR001, administered intravenously (i.v.) in adult
patients with advanced solid tumors.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02829723.
This study was a first in human, open-label, multi-center phase I/II study which
consisted of a phase I dose escalation part of BLZ945 as single agent, and of BLZ945 in
combination with PDR001, where alternative dosing regimens of BLZ945 were evaluated. The
escalation was guided by a Bayesian logistic regression model with overdose control. Once
the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) for BLZ945 as single
agent was established, a phase II part could commence, should signs of antitumor activity
had been seen during the phase I. Once the MTD/RP2D for BLZ945 in combination with PDR001
was established, a phase II part could commence.
Phase I part of the study involved patients with advanced solid tumors, including
patients with recurrent glioblastoma and patients with Hodgkin's lymphoma, and phase II
part patients with relapsed or refractory glioblastoma.
A separate Japanese single agent dose escalation was performed in order to ensure that
the safety and pharmacokinetic profiles of BLZ945 single agent were adequately
characterized in Japanese patients. The Japanese dose escalation for BLZ945 single agent
run separately from the ongoing global dose escalation. No Japanese patients were
enrolled in phase II part according to protocol. The enrollment of the Japanese cohort
was halted per investigator letter, dated 18-Jun-2021.
Lead OrganizationNovartis Pharmaceuticals Corporation