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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04237649
Recruitment Status : Terminated (Business reasons)
First Posted : January 23, 2020
Last Update Posted : September 25, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: KAZ954 Drug: PDR001 Drug: NIR178 Drug: NZV930 Early Phase 1

Detailed 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 20, 2020
Actual Primary Completion Date : September 15, 2023
Actual Study Completion Date : September 15, 2023
Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A
KAZ954
 Drug: KAZ954
KAZ954 will be administered in every arm.
Experimental: Arm B
KAZ954 + PDR001
 Drug: KAZ954
KAZ954 will be administered in every arm.

Drug: PDR001
KAZ954 + PDR001
Experimental: Arm C
KAZ954 + NIR178
 Drug: KAZ954
KAZ954 will be administered in every arm.

Drug: NIR178
KAZ954 + NIR178
Experimental: Arm D
KAZ954 + NZV930
 Drug: KAZ954
KAZ954 will be administered in every arm.

Drug: NZV930
KAZ954 + NZV930


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 35 days ]
    Dose Limiting Toxicities

  2. Incidence of adverse events and serious adverse events [ Time Frame: 36 months ]
    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.

  3. Number of participants with dose interruptions and dose reductions [ Time Frame: 36 months ]
    Number of participants with at least one dose interruption or reduction during study treatment to assess tolerability.

  4. Dose intensity of study treatment [ Time Frame: 36 months ]
    Dose intensity computed as the ratio of actual cumulative dose received and actual duration of exposure.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 36 months ]
  2. Disease Control Rate (DCR) [ Time Frame: 36 months ]
  3. Progression Free Survival (PFS) [ Time Frame: 36 months ]
    per RECIST v1.1 and iRECIST

  4. Serum concentration profiles of KAZ954 as a single agent Cmax [ Time Frame: 36 months ]
  5. Serum concentration of KAZ954 in combination with PDR001 and derived PK parameters Cmax [ Time Frame: 36 months ]
  6. Serum concentration of KAZ954 in combination with NZV930 and derived PK parameters Cmax [ Time Frame: 36 months ]
  7. Serum/Plasma concentration of KAZ954 in combination with NIR178 Cmax [ Time Frame: 36 months ]
  8. Presence and titer of anti-KAZ954 antibodies [ Time Frame: 36 months ]
  9. Presence and titer of anti-PDR001 antibodies [ Time Frame: 36 months ]
  10. Presence and titer of anti-NZV930 antibodies [ Time Frame: 36 months ]
  11. Serum concentration profiles of KAZ954 as a single agent AUC [ Time Frame: 36 months ]
  12. Serum concentration profiles of KAZ954 in combination with PDR001 and derived PK parameters AUC [ Time Frame: 36 months ]
  13. Serum concentration profiles of KAZ954 incombination with NZV930 and derived PK parameters AUC [ Time Frame: 36 months ]
  14. Serum/Plasma concentration profiles of KAZ954 in combination with NIR178 and derived PK parameters AUC [ Time Frame: 36 months ]
  15. 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 [ Time Frame: 36 months ]
    Expression of PD-L1, and determination of ORR & PFS per RECIST 1.1 and iRECIST.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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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): NCT04237649


Locations
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United States, California
University Of California Los Angeles
Los Angeles, California, United States, 90095
United States, Connecticut
Yale University Yale Cancer Center
New Haven, Connecticut, United States, 06511
United States, Illinois
Northwestern University Medical School
Chicago, Illinois, United States, 60611
United States, Missouri
Washington University School Dept. of Siteman Cancer Center
Saint Louis, Missouri, United States, 63110
United States, Texas
Uni of TX MD Anderson Cancer Cntr
Houston, Texas, United States, 77030
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
Hong Kong
Novartis Investigative Site
Shatin New Territories, Hong Kong
Italy
Novartis Investigative Site
Milano, MI, Italy, 20133
Novartis Investigative Site
Milano, MI, Italy, 20162
Japan
Novartis Investigative Site
Sunto Gun, Shizuoka, Japan, 411 8777
Singapore
Novartis Investigative Site
Singapore, Singapore, 119074
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Taiwan
Novartis Investigative Site
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04237649    
Other Study ID Numbers: CKAZ954A12101
2019-002841-39 ( EudraCT Number )
First Posted: January 23, 2020    Key Record Dates
Last Update Posted: September 25, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 ):
Solid Tumors
KAZ954
PDR001
Spartalizumab
 NIR178
NZV930
Immunotherapy
Phase I/Ib
Additional relevant MeSH terms:
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Neoplasms
Spartalizumab
Immune Checkpoint Inhibitors
 Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antineoplastic Agents