Clinical Trials /

Phase I/II 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, patients will be enrolled in the phase II part in the selected indications (glioblastoma, pancreatic cancer and triple negative breast cancer) to further assess the preliminary anti-tumor activity of BLZ945 in combination with PDR001. Should signs of anti-tumor activity be seen in the phase I dose escalation with BLZ945 as single agent, a phase II part will be opened in order to further explore BLZ945 single agent efficacy at the recommended dose.

Related Conditions:
  • Breast Carcinoma
  • Glioblastoma
  • Malignant Solid Tumor
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II 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 single agent
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, patients will be enrolled in the phase II part in the selected indications (glioblastoma, pancreatic cancer and triple negative breast cancer) to further assess the preliminary anti-tumor activity of BLZ945 in combination with PDR001. Should signs of anti-tumor activity be seen in the phase I dose escalation with BLZ945 as single agent, a phase II part will be opened in order to further explore BLZ945 single agent efficacy at the recommended dose.

Detailed Description

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 tumors in the below selected indications, with at least one measurable lesion as determined by RECIST v1.1 or RANO

    - advanced pancreatic cancer

    - advanced triple negative breast cancer,

    - recurrent glioblastoma

    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:Number of participants with Dose Limiting Toxicities (DLTs)
    Time Frame:During the first cycle (28 days) of treatment (phase I)
    Safety Issue:
    Description:To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)

    Secondary Outcome Measures

    Measure:Pharmacodynamics tumor changes from baseline of immunological markers
    Time Frame:baseline, cycle 3 day 4 to day 8 OR cycle 3 day 2 to day 4 (phase I)
    Safety Issue:
    Description:
    Measure:Progression Free Survival (PFS)
    Time Frame:From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression per RECISTv1.1 or patient withdrawal (for phase I)
    Safety Issue:
    Description:
    Measure:Best Overall Response (BOR)
    Time Frame:From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression per RECISTv1.1 or patient withdrawal (for phase I)
    Safety Issue:
    Description:
    Measure:Duration Of Rresponse (DOR)
    Time Frame:From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression per RECISTv1.1 or patient withdrawal (for phase I)
    Safety Issue:
    Description:
    Measure:PFS
    Time Frame:From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression (for phase II)
    Safety Issue:
    Description:
    Measure:BOR
    Time Frame:From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression (for phase II)
    Safety Issue:
    Description:
    Measure:DOR
    Time Frame:From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression(for phase II)
    Safety Issue:
    Description:
    Measure:Overall Survival (OS)
    Time Frame:every 12 weeks until end of study (for phase II)
    Safety Issue:
    Description:
    Measure:Pharmacokinetics (PK) Area Under the Curve (AUC) (BLZ945 single agent)
    Time Frame:Day 1, 2, 7, 8, 15 of cycle 1 OR Day 1, 2, 8, 9, 15 of cycle 1 AND Day 1 of subsequent cycle until cycle 6
    Safety Issue:
    Description:
    Measure:PK AUC (BLZ945 + PDR001)
    Time Frame:Day 1, 2, 7, 8, 15 of cycle 1 OR Day 1, 2, 8, 9, 15 of cycle 1 AND Day 1 of cycle 2 AND Day 1, 8, 15 of cycle 3 AND day 1 of subsequent cycle until cycle 6
    Safety Issue:
    Description:
    Measure:PK serum concentration (BLZ945 single agent)
    Time Frame:Day 1, 2, 7, 8, 15 of cycle 1 OR Day 1, 2, 8, 9, 15 of cycle 1 AND Day 1 of subsequent cycle until cycle 6
    Safety Issue:
    Description:
    Measure:PK serum concentration (BLZ945 + PDR001)
    Time Frame:Day 1, 2, 7, 8, 15 of cycle 1 OR Day 1, 2, 8, 9, 15 of cycle 1 AND Day 1 of cycle 2 AND Day 1, 8, 15 of cycle 3 AND day 1 of subsequent cycle until cycle 6
    Safety Issue:
    Description:
    Measure:PK Time of maximum concentration observed (Tmax) (BLZ945 single agent)
    Time Frame:Day 1, 2, 7, 8, 15 of cycle 1 OR Day 1, 2, 8, 9, 15 of cycle 1 AND Day 1 of subsequent cycle until cycle 6
    Safety Issue:
    Description:
    Measure:PK Tmax (BLZ945 + PDR001)
    Time Frame:Day 1, 2, 7, 8, 15 of cycle 1 OR Day 1, 2, 8, 9, 15 of cycle 1 AND Day 1 of cycle 2 AND Day 1, 8, 15 of cycle 3 AND day 1 of subsequent cycle until cycle 6
    Safety Issue:
    Description:
    Measure:PK peak serum concentration (Cmax) (BLZ945 + PDR001)
    Time Frame:Day 1, 2, 7, 8, 15 of cycle 1 OR Day 1, 2, 8, 9, 15 of cycle 1 AND Day 1 of cycle 2 AND Day 1, 8, 15 of cycle 3 AND day 1 of subsequent cycle until cycle 6
    Safety Issue:
    Description:
    Measure:PK Cmax (BLZ945 single agent)
    Time Frame:Day 1, 2, 7, 8, 15 of cycle 1 OR Day 1, 2, 8, 9, 15 of cycle 1 AND Day 1 of subsequent cycle until cycle 6
    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

    November 22, 2016