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

Study Overview
=================
Brief Summary
-----------------
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. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Once MTD/ RP2D was declared, glioblastoma patients were enrolled in the phase II part to further assess the preliminary anti-tumor activity of BLZ945 as single agent and in combination with PDR001.

Official Title
-----------------
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

Conditions
-----------------
Advanced Solid Tumors

Intervention / Treatment
-----------------
* Drug: BLZ945
* Drug: PDR001


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Phase I: Patients with advanced/metastatic solid tumors, with measurable or unmeasurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Phase I: Patients with a site of disease amenable to biopsy, and willing to undergo a new tumor biopsy at screening, and during treatment. Phase II: Patients with advanced/metastatic/recurrent isocitrate dehydrogenase (IDH) wild-type glioblastoma, with at least one measurable lesion as determined by RANO Other protocol defined inclusion criteria may apply Exclusion Criteria: History of severe hypersensitivity reactions to monoclonal antibodies. Impaired cardiac function or clinically significant cardiac disease. Active autoimmune disease or a documented history of autoimmune disease. Systemic steroid therapy or any immunosuppressive therapy Use of any vaccines against infectious diseases within 4 weeks of initiation of study treatment. 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. Other protocol defined exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BLZ945 single agent<br> | Drug: BLZ945<br> <br> |
| Experimental: BLZ945 + PDR001<br> | Drug: BLZ945<br> <br> Drug: PDR001<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose limiting toxicities (Phase I) | To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) | 5 years | 
| Incidence of Adverse Events (Phase I) | To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) | 5 years | 
| Incidence of Serious Adverse Events (Phase I) | To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) | 5 years | 
| Dose interruptions (Phase I) | To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) | 5 years | 
| Dose reductions (Phase I) | To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) | 5 years | 
| Dose intensity (Phase I) | To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) | 5 years | 
| Progression-free survival probability (PFSP) at 6 months (Phase II) | Percentage of participants with Progression Free Survival (PFS) at 6 months per RANO criteria | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) (Phase I) | Evaluation is based on RECISTv1.1 or irRC or RANO or iRANO | 5 years | 
| Best Overall Response (BOR) (Phase I) | Evaluation is based on RECISTv1.1 or irRC or RANO or iRANO | 5 years | 
| Disease Control Rate (DCR) (Phase I) | Evaluation is based on RECISTv1.1 or RANO | 5 years | 
| PFS (Phase II) | Evaluation is based on iRANO | 5 years | 
| BOR (Phase II) | Evaluation is based on RANO or iRANO | 5 years | 
| Duration Of Response (DOR) (Phase II) | Evaluation is based on RANO or iRANO | 5 years | 
| DCR (Phase II) | Evaluation is based on RANO or iRANO | 5 years | 
| Overall Survival (OS) (Phase II) | every 12 weeks until end of study | 6 years | 
| Incidence of AEs (Phase II) |  | 5 years | 
| Incidence of SAEs (Phase II) | Assessment to be completed at least every 28 days | 5 years | 
| Pharmacokinetics (PK) Area Under the Curve (AUC) (BLZ945 single agent) |  | 5 years | 
| PK AUC (BLZ945 + PDR001) |  | 5 years | 
| PK Time of maximum concentration observed (Tmax) (BLZ945 single agent) |  | 5 years | 
| PK Tmax (BLZ945 + PDR001) |  | 5 years | 
| PK peak serum concentration (Cmax) (BLZ945 + PDR001) |  | 5 years | 
| PK Cmax (BLZ945 single agent) |  | 5 years | 
| Concentration of anti-PDR001 antibodies (BLZ945 + PDR001) |  | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Phase I/II, BLZ945, PDR001, CSF-1R, PD-1