Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04237649
Recruitment Status : Recruiting
First Posted : January 23, 2020
Last Update Posted : July 27, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE January 17, 2020
First Posted Date  ICMJE January 23, 2020
Last Update Posted Date July 27, 2021
Actual Study Start Date  ICMJE February 20, 2020
Estimated Primary Completion Date August 12, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2021)
  • Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 35 days ]
    Dose Limiting Toxicities
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 17, 2020)
Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 36 months ]
Dose Limiting Toxicities
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2020)
  • Overall Response Rate (ORR) [ Time Frame: 36 months ]
  • Disease Control Rate (DCR) [ Time Frame: 36 months ]
  • Progression Free Survival (PFS) [ Time Frame: 36 months ]
    per RECIST v1.1 and iRECIST
  • Serum concentration profiles of KAZ954 as a single agent Cmax [ Time Frame: 36 months ]
  • Serum concentration of KAZ954 in combination with PDR001 and derived PK parameters Cmax [ Time Frame: 36 months ]
  • Serum concentration of KAZ954 in combination with NZV930 and derived PK parameters Cmax [ Time Frame: 36 months ]
  • Serum/Plasma concentration of KAZ954 in combination with NIR178 Cmax [ Time Frame: 36 months ]
  • Presence and titer of anti-KAZ954 antibodies [ Time Frame: 36 months ]
  • Presence and titer of anti-PDR001 antibodies [ Time Frame: 36 months ]
  • Presence and titer of anti-NZV930 antibodies [ Time Frame: 36 months ]
  • Serum concentration profiles of KAZ954 as a single agent AUC [ Time Frame: 36 months ]
  • Serum concentration profiles of KAZ954 in combination with PDR001 and derived PK parameters AUC [ Time Frame: 36 months ]
  • Serum concentration profiles of KAZ954 incombination with NZV930 and derived PK parameters AUC [ Time Frame: 36 months ]
  • Serum/Plasma concentration profiles of KAZ954 in combination with NIR178 and derived PK parameters AUC [ Time Frame: 36 months ]
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2020)
  • Overall Response Rate (ORR) [ Time Frame: 36 months ]
  • Disease Control Rate (DCR) [ Time Frame: 36 months ]
  • Progression Free Survival (PFS) [ Time Frame: 36 months ]
    per RECIST v1.1 and iRECIST
  • Serum concentration profiles of KAZ954 as a single agent Cmax [ Time Frame: 36 months ]
  • Serum concentration of KAZ954 in combination with PDR001 and derived PK parameters Cmax [ Time Frame: 36 months ]
  • Serum concentration of KAZ954 in combination with NZV930 and derived PK parameters Cmax [ Time Frame: 36 months ]
  • Serum/Plasma concentration of KAZ954 in combination with NIR178 Cmax [ Time Frame: 36 months ]
  • Presence and titer of anti-KAZ954 antibodies [ Time Frame: 36 months ]
  • Presence and titer of anti-PDR001 antibodies [ Time Frame: 36 months ]
  • Presence and titer of anti-NZV930 antibodies [ Time Frame: 36 months ]
  • Serum concentration profiles of KAZ954 as a single agent AUC [ Time Frame: 36 months ]
  • Serum concentration profiles of KAZ954 in combination with PDR001 and derived PK parameters AUC [ Time Frame: 36 months ]
  • Serum concentration profiles of KAZ954 incombination with NZV930 and derived PK parameters AUC [ Time Frame: 36 months ]
  • Serum/Plasma concentration profiles of KAZ954 in combination with NIR178 and derived PK parameters AUC [ Time Frame: 36 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE KAZ954 Alone and With PDR001, NZV930 and NIR178 in Advanced Solid Tumors
Official Title  ICMJE 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
Brief Summary

The purpose of this trial is 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 consists of a dose escalation part, a dose expansion part testing KAZ954 as a single agent or KAZ954 in combination with PDR001, NZV930 and NIR178. The dose escalation parts will estimate the MTD and/or RD and test different dosing schedules.

The dose expansion parts of the study will 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.

Approximately 135 adult patients with advanced solid tumors will be enrolled.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors
Intervention  ICMJE
  • Drug: KAZ954
    KAZ954 will be administered in every arm.
  • Drug: PDR001
    KAZ954 + PDR001
  • Drug: NIR178
    KAZ954 + NIR178
  • Drug: NZV930
    KAZ954 + NZV930
Study Arms  ICMJE
  • Experimental: Arm A
    KAZ954
    Intervention: Drug: KAZ954
  • Experimental: Arm B
    KAZ954 + PDR001
    Interventions:
    • Drug: KAZ954
    • Drug: PDR001
  • Experimental: Arm C
    KAZ954 + NIR178
    Interventions:
    • Drug: KAZ954
    • Drug: NIR178
  • Experimental: Arm D
    KAZ954 + NZV930
    Interventions:
    • Drug: KAZ954
    • Drug: NZV930
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 17, 2020)
145
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 12, 2024
Estimated Primary Completion Date August 12, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Italy,   Japan,   Singapore,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04237649
Other Study ID Numbers  ICMJE CKAZ954A12101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP