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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 )

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.


Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: BLZ945 Drug: PDR001 Phase 1 Phase 2

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Study Type : Interventional
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 21, 2016
Estimated Primary Completion Date : June 17, 2021
Estimated Study Completion Date : June 17, 2021

Arm Intervention/treatment
Experimental: BLZ945 single agent Drug: BLZ945
Experimental: BLZ945 + PDR001 Drug: BLZ945
Drug: PDR001



Primary Outcome Measures :
  1. Incidence of Dose limiting toxicities (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)

  2. Incidence of Adverse Events (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)

  3. Incidence of Serious Adverse Events (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)

  4. Dose interruptions (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)

  5. Dose reductions (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)

  6. Dose intensity (Phase I) [ Time Frame: 5 years ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D)

  7. 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


Secondary Outcome Measures :
  1. CD163 (Phase I) [ Time Frame: 5 years ]
    On treatment versus baseline comparison of pharmacodynamics markers expressions by immunohistochemistry

  2. CD8 (Phase I) [ Time Frame: 5 years ]
    On treatment versus baseline comparison of pharmacodynamics markers expressions by immunohistochemistry

  3. Progression Free Survival (PFS) (Phase I) [ Time Frame: 5 years ]
    Evaluation is based on RECISTv1.1 or irRC or RANO or iRANO

  4. Best Overall Response (BOR) (Phase I) [ Time Frame: 5 years ]
    Evaluation is based on RECISTv1.1 or irRC or RANO or iRANO

  5. Disease Control Rate (DCR) (Phase I) [ Time Frame: 5 years ]
    Evaluation is based on RECISTv1.1 or RANO

  6. PFS (Phase II) [ Time Frame: 5 years ]
    Evaluation is based on iRANO

  7. BOR (Phase II) [ Time Frame: 5 years ]
    Evaluation is based on RANO or iRANO

  8. Duration Of Response (DOR) (Phase II) [ Time Frame: 5 years ]
    Evaluation is based on RANO or iRANO

  9. DCR (Phase II) [ Time Frame: 5 years ]
    Evaluation is based on RANO or iRANO

  10. Overall Survival (OS) (Phase II) [ Time Frame: 6 years ]
    every 12 weeks until end of study

  11. Incidence of AEs (Phase II) [ Time Frame: 5 years ]
  12. Incidence of SAEs (Phase II) [ Time Frame: 5 years ]
    Assessment to be completed at least every 28 days

  13. Pharmacokinetics (PK) Area Under the Curve (AUC) (BLZ945 single agent) [ Time Frame: 5 years ]
  14. PK AUC (BLZ945 + PDR001) [ Time Frame: 5 years ]
  15. PK Time of maximum concentration observed (Tmax) (BLZ945 single agent) [ Time Frame: 5 years ]
  16. PK Tmax (BLZ945 + PDR001) [ Time Frame: 5 years ]
  17. PK peak serum concentration (Cmax) (BLZ945 + PDR001) [ Time Frame: 5 years ]
  18. PK Cmax (BLZ945 single agent) [ Time Frame: 5 years ]
  19. Concentration of anti-PDR001 antibodies (BLZ945 + PDR001) [ Time Frame: 5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02829723


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Tennessee
Sarah Cannon Research Institute Sarah Cannon Research Recruiting
Nashville, Tennessee, United States, 37203
Contact: John Kilgore    615-289-9227    john.Kilgore@sarahcannon.com   
Principal Investigator: Todd M. Bauer         
United States, Texas
UT M.D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Fiona Ouyang    713-563-9033    fouyang@mdanderson.org   
Principal Investigator: Aung Naing         
Cancer Therapy and Research Center UT Health Science Center Recruiting
San Antonio, Texas, United States, 78229
Contact: Maghan Rios    210-450-3838    riosm7@uthscsa.eud   
Principal Investigator: John Sarantopoulos         
Israel
Novartis Investigative Site Recruiting
Tel Aviv, Israel, 6423906
Italy
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Japan
Novartis Investigative Site Recruiting
Nagoya, Aichi, Japan, 466 8560
Novartis Investigative Site Recruiting
Koto ku, Tokyo, Japan, 135 8550
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Spain
Novartis Investigative Site Recruiting
Hospitalet de LLobregat, Catalunya, Spain, 08907
Novartis Investigative Site Recruiting
Madrid, Spain, 28041
Taiwan
Novartis Investigative Site Recruiting
Tainan, Taiwan, 70403
Novartis Investigative Site Recruiting
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02829723    
Other Study ID Numbers: CBLZ945X2101
2015-005806-12 ( EudraCT Number )
First Posted: July 12, 2016    Key Record Dates
Last Update Posted: September 9, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Phase I/II
BLZ945
PDR001
CSF-1R
PD-1
Additional relevant MeSH terms:
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Neoplasms