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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02829723
Recruitment Status : Recruiting
First Posted : July 12, 2016
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE July 8, 2016
First Posted Date  ICMJE July 12, 2016
Last Update Posted Date September 9, 2020
Actual Study Start Date  ICMJE October 21, 2016
Estimated Primary Completion Date June 17, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 23, 2020)
  • Incidence of Dose limiting toxicities (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
  • Incidence of Adverse Events (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
  • Incidence of Serious Adverse Events (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
  • Dose interruptions (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
  • Dose reductions (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
  • Dose intensity (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
  • Progression-free survival probability (PFSP) at 6 months (Phase II) [ Time Frame: 6 months ]
    Percentage of participants with Progression Free Survival (PFS) at 6 months per RANO criteria
Original Primary Outcome Measures  ICMJE
 (submitted: July 8, 2016)
  • Number of participants with Dose Limiting Toxicities (DLTs) [ Time Frame: During the first cycle (28 days) of treatment (phase I) ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)
  • Progression Free Survival (PFS) per RECIST v.1.1 or RANO criteria [ Time Frame: From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression per irRC or patient withdrawal (for phase II) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2020)
  • CD163 (Phase I) [ Time Frame: 5 years ]
    On treatment versus baseline comparison of pharmacodynamics markers expressions by immunohistochemistry
  • CD8 (Phase I) [ Time Frame: 5 years ]
    On treatment versus baseline comparison of pharmacodynamics markers expressions by immunohistochemistry
  • Progression Free Survival (PFS) (Phase I) [ Time Frame: 5 years ]
    Evaluation is based on RECISTv1.1 or irRC or RANO or iRANO
  • Best Overall Response (BOR) (Phase I) [ Time Frame: 5 years ]
    Evaluation is based on RECISTv1.1 or irRC or RANO or iRANO
  • Disease Control Rate (DCR) (Phase I) [ Time Frame: 5 years ]
    Evaluation is based on RECISTv1.1 or RANO
  • PFS (Phase II) [ Time Frame: 5 years ]
    Evaluation is based on iRANO
  • BOR (Phase II) [ Time Frame: 5 years ]
    Evaluation is based on RANO or iRANO
  • Duration Of Response (DOR) (Phase II) [ Time Frame: 5 years ]
    Evaluation is based on RANO or iRANO
  • DCR (Phase II) [ Time Frame: 5 years ]
    Evaluation is based on RANO or iRANO
  • Overall Survival (OS) (Phase II) [ Time Frame: 6 years ]
    every 12 weeks until end of study
  • Incidence of AEs (Phase II) [ Time Frame: 5 years ]
  • Incidence of SAEs (Phase II) [ Time Frame: 5 years ]
    Assessment to be completed at least every 28 days
  • Pharmacokinetics (PK) Area Under the Curve (AUC) (BLZ945 single agent) [ Time Frame: 5 years ]
  • PK AUC (BLZ945 + PDR001) [ Time Frame: 5 years ]
  • PK Time of maximum concentration observed (Tmax) (BLZ945 single agent) [ Time Frame: 5 years ]
  • PK Tmax (BLZ945 + PDR001) [ Time Frame: 5 years ]
  • PK peak serum concentration (Cmax) (BLZ945 + PDR001) [ Time Frame: 5 years ]
  • PK Cmax (BLZ945 single agent) [ Time Frame: 5 years ]
  • Concentration of anti-PDR001 antibodies (BLZ945 + PDR001) [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2016)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • PFS [ Time Frame: From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression (for phase II) ]
  • BOR [ Time Frame: From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression (for phase II) ]
  • DOR [ Time Frame: From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression(for phase II) ]
  • Overall Survival (OS) [ Time Frame: every 12 weeks until end of study (for phase II) ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of BLZ945 Single Agent or BLZ945 in Combination With PDR001 in Advanced Solid Tumors
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Drug: BLZ945
  • Drug: PDR001
Study Arms  ICMJE
  • Experimental: BLZ945 single agent
    Intervention: Drug: BLZ945
  • Experimental: BLZ945 + PDR001
    Interventions:
    • Drug: BLZ945
    • Drug: PDR001
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 8, 2020)
200
Original Estimated Enrollment  ICMJE
 (submitted: July 8, 2016)
151
Estimated Study Completion Date  ICMJE June 17, 2021
Estimated Primary Completion Date June 17, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Japan,   Israel,   Italy,   Singapore,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02829723
Other Study ID Numbers  ICMJE CBLZ945X2101
2015-005806-12 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP