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

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

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: KAZ954; Drug: PDR001; Drug: NIR178; Drug: NZV930

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 Type: Interventional
• Enrollment (Actual): 77
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
• Hong Kong
  • Shatin New Territories, Hong Kong
    • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
• Japan
  • Shizuoka
    • Sunto Gun, Shizuoka, Japan, 411 8777
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
• Spain
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University Yale Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Medical School
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School Dept. of Siteman Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Uni of TX MD Anderson Cancer Cntr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting Toxicities (DLTs)	Dose Limiting Toxicities	35 days
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
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
Dose intensity of study treatment	Dose intensity computed as the ratio of actual cumulative dose received and actual duration of exposure.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)		36 months
Disease Control Rate (DCR)		36 months
Progression Free Survival (PFS)	per RECIST v1.1 and iRECIST	36 months
Serum concentration profiles of KAZ954 as a single agent Cmax		36 months
Serum concentration of KAZ954 in combination with PDR001 and derived PK parameters Cmax		36 months
Serum concentration of KAZ954 in combination with NZV930 and derived PK parameters Cmax		36 months
Serum/Plasma concentration of KAZ954 in combination with NIR178 Cmax		36 months
Presence and titer of anti-KAZ954 antibodies		36 months
Presence and titer of anti-PDR001 antibodies		36 months
Presence and titer of anti-NZV930 antibodies		36 months
Serum concentration profiles of KAZ954 as a single agent AUC		36 months
Serum concentration profiles of KAZ954 in combination with PDR001 and derived PK parameters AUC		36 months
Serum concentration profiles of KAZ954 incombination with NZV930 and derived PK parameters AUC		36 months
Serum/Plasma concentration profiles of KAZ954 in combination with NIR178 and derived PK parameters AUC		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	Expression of PD-L1, and determination of ORR & PFS per RECIST 1.1 and iRECIST.	36 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2020
• Primary Completion (Actual): September 15, 2023
• Study Completion (Actual): September 15, 2023

Study Registration Dates

• First Submitted: January 17, 2020
• First Submitted That Met QC Criteria: January 17, 2020
• First Posted (Actual): January 23, 2020

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Immunotherapy; Solid Tumors; PDR001; Spartalizumab; KAZ954; NIR178; NZV930; Phase I/Ib
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Spartalizumab
• Other Study ID Numbers: CKAZ954A12101; 2019-002841-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No