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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04237649
Other study ID # CKAZ954A12101
Secondary ID 2019-002841-39
Status Terminated
Phase Early Phase 1
First received
Last updated
Start date February 20, 2020
Est. completion date September 15, 2023

Study information

Verified date September 2023
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary objective of the trial was to characterize the safety, tolerability, and maximum tolerated dose (MTD)/recommended dose (RD) for expansion of single agent KAZ954 and KAZ954 in combination with PDR001, NIR178 and NZV930.


Description:

The purpose of this trial was to explore the clinical utility of several therapies in patients with advanced cancer. This is a multi-center, open-label Phase I/Ib study. The study consisted of a dose escalation part and a dose expansion part testing KAZ954 as a single agent or KAZ954 in combination with PDR001, NZV930 and NIR178. The dose escalation part estimated the MTD and/or RD and tested different dosing schedules. The dose escalation arm KAZ954 + NZV930 was not opened. The dose expansion part of the study was planned to use the MTD/RDE determined in the dose escalation part to assess the activity, safety and tolerability of the investigational products in patients with specific types of cancer. The dose expansion part of the study was not started.


Recruitment information / eligibility

Status Terminated
Enrollment 77
Est. completion date September 15, 2023
Est. primary completion date September 15, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 99 Years
Eligibility Inclusion Criteria: Patients with metastatic and/or advanced malignancies not amenable to curative treatment by surgery. 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 and during the study. ECOG Performance Status of <2. Exclusion Criteria: Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require concurrent treatment - including surgery, radiation and/or corticosteroids. History of severe hypersensitivity reaction to any ingredient of study drug(s) and other mAbs and/or their excipients. Impaired cardiac function HIV Known history of tuberculosis Systemic chronic steroid therapy Other protocol-defined inclusion/exclusion criteria may apply.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
KAZ954
KAZ954 will be administered in every arm.
PDR001
KAZ954 + PDR001
NIR178
KAZ954 + NIR178
NZV930
KAZ954 + NZV930

Locations

Country Name City State
Canada Novartis Investigative Site Toronto Ontario
Hong Kong Novartis Investigative Site Shatin New Territories
Italy Novartis Investigative Site Milano MI
Italy Novartis Investigative Site Milano MI
Japan Novartis Investigative Site Sunto Gun Shizuoka
Singapore Novartis Investigative Site Singapore
Spain Novartis Investigative Site Barcelona Catalunya
Taiwan Novartis Investigative Site Taipei
United States Northwestern University Medical School Chicago Illinois
United States Uni of TX MD Anderson Cancer Cntr Houston Texas
United States University Of California Los Angeles Los Angeles California
United States Yale University Yale Cancer Center New Haven Connecticut
United States Washington University School Dept. of Siteman Cancer Center Saint Louis Missouri

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Hong Kong,  Italy,  Japan,  Singapore,  Spain,  Taiwan, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of Dose Limiting Toxicities (DLTs) Dose Limiting Toxicities 35 days
Primary Incidence of adverse events and serious adverse events Incidence of adverse events is defined as number of participants with adverse events (AEs) and serious adverse events (SAEs), including changes from baseline in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs. 36 months
Primary Number of participants with dose interruptions and dose reductions Number of participants with at least one dose interruption or reduction during study treatment to assess tolerability. 36 months
Primary Dose intensity of study treatment Dose intensity computed as the ratio of actual cumulative dose received and actual duration of exposure. 36 months
Secondary Overall Response Rate (ORR) 36 months
Secondary Disease Control Rate (DCR) 36 months
Secondary Progression Free Survival (PFS) per RECIST v1.1 and iRECIST 36 months
Secondary Serum concentration profiles of KAZ954 as a single agent Cmax 36 months
Secondary Serum concentration of KAZ954 in combination with PDR001 and derived PK parameters Cmax 36 months
Secondary Serum concentration of KAZ954 in combination with NZV930 and derived PK parameters Cmax 36 months
Secondary Serum/Plasma concentration of KAZ954 in combination with NIR178 Cmax 36 months
Secondary Presence and titer of anti-KAZ954 antibodies 36 months
Secondary Presence and titer of anti-PDR001 antibodies 36 months
Secondary Presence and titer of anti-NZV930 antibodies 36 months
Secondary Serum concentration profiles of KAZ954 as a single agent AUC 36 months
Secondary Serum concentration profiles of KAZ954 in combination with PDR001 and derived PK parameters AUC 36 months
Secondary Serum concentration profiles of KAZ954 incombination with NZV930 and derived PK parameters AUC 36 months
Secondary Serum/Plasma concentration profiles of KAZ954 in combination with NIR178 and derived PK parameters AUC 36 months
Secondary Assess the correlation between PD-L1 expression level in tumor using a validated assay and response to KAZ954 and in combo with PDR001, NIR178 or NZV930 Expression of PD-L1, and determination of ORR & PFS per RECIST 1.1 and iRECIST. 36 months
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