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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02936102
• Other study ID #: CFAZ053X2101
• Secondary ID: 2016-001470-15
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 20, 2016
• Est. completion date: November 14, 2024

Study information

• Verified date: March 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 154
• Est. completion date: November 14, 2024
• Est. primary completion date: November 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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: 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: TNBC/ Chordoma/ ASPS

• 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 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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Chordoma
• Chordoma and Alveolar Soft Part Sarcoma
• Sarcoma, Alveolar Soft Part
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• FAZ053
Anti-PD-L1 Antibody
• PDR001
Anti-PD-1 Antibody

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Toronto	Ontario
France	Novartis Investigative Site	Toulouse
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Modena	MO
Japan	Novartis Investigative Site	Koto ku	Tokyo
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Sevilla	Andalucia
Taiwan	Novartis Investigative Site	Taipei
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Ctr .	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  France,  Israel,  Italy,  Japan,  Singapore,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs) and laboratory parameters qualifying and reported as AEs.	throughout the study and up to 150 days after end of treatment (up to approximately 46 months)
Primary	Incidence of Dose Limiting Toxicities (DLTs)	A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade = 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first 21 days of treatment with FAZ053 alone or within the first 42 days when FAZ053 is given in combination with PDR001 during the dose escalation part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.	21 days (single agent FAZ053) and 42 days (FAZ053+PDR001)
Primary	Dose interruptions and reductions	Number of participants with dose interruptions and reductions as a measure of tolerability.	Up to approximately 41 months
Primary	Dose intensity	Dose intensity is defined as actual dose received divided by actual duration of exposure.	Up to approximately 41 months
Secondary	Serum concentration-time profiles of FAZ053 as single agent and FAZ053 in combination with PDR001.		41 months
Secondary	Presence of anti-FAZ053 and anti-PDR001.		41 months
Secondary	Concentration of anti-FAZ053 and anti-PDR001.		41 months
Secondary	Receptor Occupancy (RO) profiles when FAZ053 is given as single agent.		41 months
Secondary	Total soluble/shed PD-L1 concentration-time profiles when FAZ053 is given as single agent and for FAZ053 in combination with PDR001.		41 months
Secondary	Histopathology of tumor infiltrating lymphocytes (TILs) by hematoxylin.		41 months
Secondary	Histopathology of tumor infiltrating lymphocytes (TILs) by eosin (H&E) stain.		41 months
Secondary	Overall response rate (ORR) per RECIST v1.1		41 months
Secondary	Best overall response per RECIST v1.1		41 months
Secondary	Disease control rate per RECIST 1.1		41 months
Secondary	Progression free survival (PFS) per RECIST 1.1		41 months
Secondary	Duration of response per RECIST 1.1		41 months
Secondary	Overall response rate (ORR) per immune related Response Criteria (irRC).		41 months
Secondary	Progression free survival (PFS) per immune related Response Criteria (irRC).		41 months
Secondary	Characterization of Tumor Infiltrating Lymphocytes (TILs) by Immunohistochemistry (IHC)		41 months
Secondary	Characterization of myeloid cell infiltrate by IHC.		41 months
Secondary	Area under the curve (AUC) for FAZ053 as single agent and FAZ053 in combination with PDR001.		41 months
Secondary	Cmax for FAZ053 as single agent and FAZ053 in combination with PDR001.		41 months
Secondary	Tmax for FAZ053 as single agent and FAZ053 in combination with PDR001.		41 months
Secondary	Half-life for FAZ053 as single agent and FAZ053 in combination with PDR001.		41 months
Secondary	Clast for FAZ053 as single agent and FAZ053 in combination with PDR001.		41 months
Secondary	Tlast for FAZ053 as single agent and FAZ053 in combination with PDR001.		41 months