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A Study of FAZ053 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies.

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ClinicalTrials.gov Identifier: NCT02936102
Recruitment Status : Recruiting
First Posted : October 18, 2016
Last Update Posted : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

The purpose of this "first-in-human" study of FAZ053 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of FAZ053 administered Intravenously (i.v.)as a single agent or in combination with PDR001 in adult patients with advanced solid tumors.

By blocking the interaction between Programmed Death Ligand-1 (PD-L1) and its receptors, Programmed Death-1 (PD-1) and B7.1, FAZ053 inhibits the PD-L1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells.

This study has been designed as a Phase I, open-label, multi-center study with a dose escalation part of FAZ053 as single agent and in combination with PDR001, followed by a dose expansion part of FAZ053 as single agent and in combination with PDR001.

FAZ053 will initially be dosed every three weeks. A less frequent dosing regimen such as every 6 weeks may be evaluated in parallel.

A patient may continue treatment with FAZ053 single agent or in combination with PDR001 until the patient experiences unacceptable toxicity, confirmed disease progression per immune related Response Criteria and/or treatment is discontinued at the discretion of the investigator or the patient.


Condition or disease Intervention/treatment Phase
Advanced Solid Tumors, Non-Small Cell Lung Carcinoma, Triple Negative Breast Cancer, Endometrial Cancer, Anaplastic Thyroid Cancer Drug: FAZ053 Drug: PDR001 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 212 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Multi-center Dose Escalation Study of FAZ053 as Single Agent and in Combination With PDR001 in Adult Patients With Advanced Malignancies
Actual Study Start Date : October 20, 2016
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : February 28, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: FAZ053 single agent Drug: FAZ053
Anti-PD-L1 Antibody

Experimental: FAZ053 + PDR001 Drug: FAZ053
Anti-PD-L1 Antibody

Drug: PDR001
Anti-PD-1 Antibody




Primary Outcome Measures :
  1. Number of participants with Adverse Events (AEs) as a measure of safety and tolerability [ Time Frame: throughout the study up to 150 days after end of treatment ]

Secondary Outcome Measures :
  1. Serum concentration-time profiles of FAZ053 as single agent and FAZ053 in combination with PDR001. [ Time Frame: 35 months ]
  2. Presence of anti-FAZ053 and anti-PDR001. [ Time Frame: 35 months ]
  3. Concentration of anti-FAZ053 and anti-PDR001. [ Time Frame: 35 months ]
  4. Receptor Occupancy (RO) profiles when FAZ053 is given as single agent and for FAZ053 in combination with PDR001. [ Time Frame: 35 months ]
  5. Total soluble/shed PD-L1 concentration-time profiles when FAZ053 is given as single agent and for FAZ053 in combination with PDR001. [ Time Frame: 35 months ]
  6. Histopathology of tumor infiltrating lymphocytes (TILs) by hematoxylin. [ Time Frame: 35 months ]
  7. Histopathology of tumor infiltrating lymphocytes (TILs) by eosin (H&E) stain. [ Time Frame: 35 months ]
  8. Overall response rate (ORR) per RECIST v1.1 [ Time Frame: 35 months ]
  9. Best overall response per RECIST v1.1 [ Time Frame: 35 months ]
  10. Disease control rate per RECIST 1.1 [ Time Frame: 35 months ]
  11. Progression free survival (PFS) per RECIST 1.1 [ Time Frame: 35 months ]
  12. Duration of response per RECIST 1.1 [ Time Frame: 35 months ]
  13. Overall response rate (ORR) per immune related Response Criteria (irRC). [ Time Frame: 35 months ]
  14. Progression free survival (PFS) per immune related Response Criteria (irRC). [ Time Frame: 35 months ]
  15. Characterization of Tumor Infiltrating Lymphocytes (TILs) by Immunohistochemistry (IHC) [ Time Frame: 35 months ]
  16. Characterization of myeloid cell infiltrate by IHC (CD8,FoxP3, CD163,CD68). [ Time Frame: 35 months ]
  17. Area under the curve (AUC) for FAZ053 as single agent and FAZ053 in combination with PDR001. [ Time Frame: 35 months ]
  18. Cmax for FAZ053 as single agent and FAZ053 in combination with PDR001. [ Time Frame: 35 months ]
  19. Tmax for FAZ053 as single agent and FAZ053 in combination with PDR001. [ Time Frame: 35 months ]
  20. Half-life for FAZ053 as single agent and FAZ053 in combination with PDR001. [ Time Frame: 35 months ]
  21. Clast for FAZ053 as single agent and FAZ053 in combination with PDR001. [ Time Frame: 35 months ]
  22. Tlast for FAZ053 as single agent and FAZ053 in combination with PDR001. [ Time Frame: 35 months ]


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:

  • Written informed consent prior to any procedure.
  • Dose escalation cohorts of FAZ053 single agent and FAZ053 in combination with PDR001: Patients with advanced/metastatic solid tumors with measurable or non-measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 who may or may not have received prior treatment with an immune checkpoint inhibitor, who have progressed despite standard therapy, or for whom no standard therapy is available.
  • Dose expansion groups of FAZ053 single agent and FAZ053 in combination with PDR001: Patients with advanced/metastatic solid tumors with at least one measurable lesion as determined by RECIST version 1.1 who may or may not have received prior treatment with an immune checkpoint inhibitor (for FAZ053 single agent no treatment with an anti-PD-L1 inhibitor is permitted), who have progressed despite standard therapy, or for whom no standard therapy is available and fit into one of the following groups:
  • FAZ053 single agent: NSCLC/ TNBC/ Endometrial cancer / Anaplastic thyroid cancer/Selected indication(s) in dose expansion group every 6 Weeks (Q6W) dosing regimen
  • FAZ053 in combination with PDR001: NSCLC/TNBC / Selected indication(s) in dose expansion group Q6W dosing regimen
  • Performance Status (PS) ≤ 2:
  • Patient must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening/ baseline or at molecular pre-screening if applicable, and during therapy on this study.

Exclusion Criteria:

  • Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local CNS-directed therapy (e.g. radiotherapy or surgery) or increasing doses of corticosteroids within the prior 2 weeks. Patients with treated brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to study enrollment) and off of steroids for at least 2 weeks before administration of any study treatment.
  • History of severe hypersensitivity to study treatment excipients and additives or other monoclonal antibodies (mAbs) and/or their excipients.
  • Active, known or suspected autoimmune disease. Patients with vitiligo, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger should not be excluded. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
  • Treatment with cytotoxic or targeted antineoplastics within 3 weeks of initiation of study treatment. For cytotoxic agents that have major delayed toxicity a washout period of one cycle is indicated (examples are nitrosoureas and mitomycin C which typically require a 6 week washout). Prior antibodies or immunotherapies require a 6 week washout.
  • Patients receiving systemic chronic steroid therapy or any immunosuppressive therapy (≥ 10mg/day prednisone or equivalent). Topical, inhaled, nasal and ophthalmic steroids are allowed.
  • Active infection requiring systemic antibiotic therapy.

Other protocol-defined inclusion/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): NCT02936102


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

Locations
United States, California
Novartis Investigative Site Recruiting
Santa Monica, California, United States, 90404
United States, New York
Novartis Investigative Site Recruiting
New York, New York, United States, 10065
Contact: Afra Yehwalashet    646-888-5341    yehwalaa@mskcc.org   
Principal Investigator: Ayca Gucalp         
United States, Texas
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77030
Contact: Anjali Raina    713-563-2632    ARaina@mdanderson.org   
Principal Investigator: Filip Janku         
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
France
Novartis Investigative Site Recruiting
Toulouse Cedex 9, France, 31059
Germany
Novartis Investigative Site Recruiting
Jena, Germany, 07740
Israel
Novartis Investigative Site Recruiting
Tel Aviv, Israel, 64239
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Recruiting
Modena, MO, Italy, 41124
Japan
Novartis Investigative Site Recruiting
Koto-ku, Tokyo, Japan, 135 8550
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 119228
Spain
Novartis Investigative Site Recruiting
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02936102     History of Changes
Other Study ID Numbers: CFAZ053X2101
2016-001470-15 ( EudraCT Number )
First Posted: October 18, 2016    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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
FAZ053
PDR001
Checkpoint inhibitor
PD-L1
PD-1

Additional relevant MeSH terms:
Endometrial Neoplasms
Thyroid Neoplasms
Triple Negative Breast Neoplasms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Thyroid Carcinoma, Anaplastic
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Endocrine Gland Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Thyroid Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type