A Study of BLZ945 Single Agent or BLZ945 in Combination With PDR001 in Advanced Solid Tumors

A Phase I/II, Open-label, Multi-center Study of the Safety and Efficacy of BLZ945 as Single Agent and in Combination With PDR001 in Adults Patients With Advanced Solid Tumors

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.

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.

Inclusion Criteria:

1. Phase I: Patients with advanced/metastatic solid tumors including relapsed or refractory (r/r) glioblastoma and r/r lymphoma, with measurable or unmeasurable disease as determined by the respective response evaluation criteria.
2. Phase I: Patients with a site of disease amenable to biopsy, and willing to undergo a new tumor biopsy at screening, and during treatment.
3. Phase II: Patients with advanced/metastatic/recurrent isocitrate dehydrogenase (IDH) wild-type glioblastoma, with at least one measurable lesion as determined by RANO

Exclusion Criteria:

1. History of severe hypersensitivity reactions to monoclonal antibodies.
2. Impaired cardiac function or clinically significant cardiac disease.
3. Active autoimmune disease or a documented history of autoimmune disease.
4. Systemic steroid therapy or any immunosuppressive therapy
5. Use of any vaccines against infectious diseases within 4 weeks of initiation of study treatment.
6. Patient receiving treatment with medications that either strong inducers or inhibitors of CYP2C8 or CYP3A4/5, or patients receiving medication that prohibits proton pump inhibitors and that cannot be discontinued at least 1 week prior to start of treatment and for the duration of the study.
7. Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within the prior 2 weeks before start of study treatment (not applicable for glioblastoma).