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Phase I/II Study of BLZ945 Single Agent or BLZ945 in Combination With PDR001 in Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT02829723
Recruitment Status : Recruiting
First Posted : July 12, 2016
Last Update Posted : July 12, 2018
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, 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.


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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 151 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 19, 2019
Estimated Study Completion Date : June 19, 2019

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



Primary Outcome Measures :
  1. 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)

  2. 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) ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. PFS [ Time Frame: From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression (for phase II) ]
  6. BOR [ Time Frame: From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression (for phase II) ]
  7. DOR [ Time Frame: From cycle 1, every 2 cycles up to cycle 11, then every 3 cycles until progression(for phase II) ]
  8. Overall Survival (OS) [ Time Frame: every 12 weeks until end of study (for phase II) ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]


Information from the National Library of Medicine

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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 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.


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
Novartis Investigative Site Recruiting
Nashville, Tennessee, United States, 37203
Contact: Jeremy Stewart    615-289-9227    jeremy.stewart@scresearch.net   
Principal Investigator: Todd M. Bauer         
United States, Texas
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77030
Contact: Lacey McQuinn    713-563-9033    lmcquinn@mdanderson.org   
Principal Investigator: Aung Naing         
Novartis Investigative Site Recruiting
San Antonio, Texas, United States, 78229
Contact: Kathleen Rodriguez    210-450-3838    rodriguezk3@uthscsa.edu   
Principal Investigator: John Sarantopoulos         
Italy
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Japan
Novartis Investigative Site Recruiting
Nagoya, Aichi, Japan, 466 8560
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Spain
Novartis Investigative Site Recruiting
Hospitalet de LLobregat, Catalunya, Spain, 08907
Taiwan
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     History of Changes
Other Study ID Numbers: CBLZ945X2101
2015-005806-12 ( EudraCT Number )
First Posted: July 12, 2016    Key Record Dates
Last Update Posted: July 12, 2018
Last Verified: July 2018
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