KAZ954 Alone and With PDR001, NZV930 and NIR178 in Advanced Solid Tumors

Solid Tumors Clinical Trial

Official title:

A Phase I/Ib, Open-label, Multi-center, Study of KAZ954 as a Single Agent and in Combination With Spartalizumab, NZV930 and NIR178 in Patients With Advanced Solid Tumors

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
• 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
• 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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

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