Clinical Trials /

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

NCT02829723

Description:

The purpose of this first-in-human (FIH) study of BLZ945 given as a single agent or in combination with PDR001 is 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 will be guided by a Bayesian logistic regression model with overdose control. Once MTD/ RP2D is declared, glioblastoma patients will be enrolled in the phase II part to further assess the preliminary anti-tumor activity of BLZ945 as single agent and in combination with PDR001.

Related Conditions:
  • Glioblastoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of BLZ945 Single Agent or BLZ945 in Combination With PDR001 in Advanced Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: CBLZ945X2101
  • SECONDARY ID: 2015-005806-12
  • NCT ID: NCT02829723

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
BLZ945BLZ945 + PDR001
PDR001BLZ945 + PDR001

Purpose

The purpose of this first-in-human (FIH) study of BLZ945 given as a single agent or in combination with PDR001 is 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 will be guided by a Bayesian logistic regression model with overdose control. Once MTD/ RP2D is declared, glioblastoma patients will be enrolled in the phase II part to further assess the preliminary anti-tumor activity of BLZ945 as single agent and in combination with PDR001.

Trial Arms

NameTypeDescriptionInterventions
BLZ945 single agentExperimental
  • BLZ945
BLZ945 + PDR001Experimental
  • BLZ945
  • PDR001

Eligibility Criteria

        Inclusion Criteria:

          1. 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

          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

        Other protocol defined inclusion criteria may apply

        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.

        Other protocol defined exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Dose limiting toxicities (Phase I)
Time Frame:5 years
Safety Issue:
Description:To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)

Secondary Outcome Measures

Measure:CD163 (Phase I)
Time Frame:5 years
Safety Issue:
Description:On treatment versus baseline comparison of pharmacodynamics markers expressions by immunohistochemistry
Measure:CD8 (Phase I)
Time Frame:5 years
Safety Issue:
Description:On treatment versus baseline comparison of pharmacodynamics markers expressions by immunohistochemistry
Measure:Progression Free Survival (PFS) (Phase I)
Time Frame:5 years
Safety Issue:
Description:Evaluation is based on RECISTv1.1 or irRC or RANO or iRANO
Measure:Best Overall Response (BOR) (Phase I)
Time Frame:5 years
Safety Issue:
Description:Evaluation is based on RECISTv1.1 or irRC or RANO or iRANO
Measure:Disease Control Rate (DCR) (Phase I)
Time Frame:5 years
Safety Issue:
Description:Evaluation is based on RECISTv1.1 or RANO
Measure:PFS (Phase II)
Time Frame:5 years
Safety Issue:
Description:Evaluation is based on iRANO
Measure:BOR (Phase II)
Time Frame:5 years
Safety Issue:
Description:Evaluation is based on RANO or iRANO
Measure:Duration Of Response (DOR) (Phase II)
Time Frame:5 years
Safety Issue:
Description:Evaluation is based on RANO or iRANO
Measure:DCR (Phase II)
Time Frame:5 years
Safety Issue:
Description:Evaluation is based on RANO or iRANO
Measure:Overall Survival (OS) (Phase II)
Time Frame:6 years
Safety Issue:
Description:every 12 weeks until end of study
Measure:Incidence of AEs (Phase II)
Time Frame:5 years
Safety Issue:
Description:
Measure:Incidence of SAEs (Phase II)
Time Frame:5 years
Safety Issue:
Description:Assessment to be completed at least every 28 days
Measure:Pharmacokinetics (PK) Area Under the Curve (AUC) (BLZ945 single agent)
Time Frame:5 years
Safety Issue:
Description:
Measure:PK AUC (BLZ945 + PDR001)
Time Frame:5 years
Safety Issue:
Description:
Measure:PK Time of maximum concentration observed (Tmax) (BLZ945 single agent)
Time Frame:5 years
Safety Issue:
Description:
Measure:PK Tmax (BLZ945 + PDR001)
Time Frame:5 years
Safety Issue:
Description:
Measure:PK peak serum concentration (Cmax) (BLZ945 + PDR001)
Time Frame:5 years
Safety Issue:
Description:
Measure:PK Cmax (BLZ945 single agent)
Time Frame:5 years
Safety Issue:
Description:
Measure:Concentration of anti-PDR001 antibodies (BLZ945 + PDR001)
Time Frame:5 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Phase I/II
  • BLZ945
  • PDR001
  • CSF-1R
  • PD-1

Last Updated

April 23, 2020