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

• ClinicalTrials.gov Identifier: NCT04237649
• Recruitment Status: Terminated
• First Posted: January 23, 2020
• Last Update Posted: September 25, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: January 17, 2020
• First Posted Date: January 23, 2020
• Last Update Posted Date: September 25, 2023
• Actual Study Start Date: February 20, 2020
• Actual Primary Completion Date: September 15, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: January 17, 2020)

Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 36 months ]

Dose Limiting Toxicities

Current Secondary Outcome Measures (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 (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: KAZ954 Alone and With PDR001, NZV930 and NIR178 in Advanced Solid Tumors
• 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
• 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.

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
• Study Phase: Early Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumors

Intervention

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

Study Arms

• 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

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 14, 2023): 77
• Original Estimated Enrollment (submitted: January 17, 2020): 145
• Actual Study Completion Date: September 15, 2023
• Actual Primary Completion Date: September 15, 2023 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Hong Kong, Italy, Japan, Singapore, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT04237649
• Other Study ID Numbers: CKAZ954A12101; 2019-002841-39 ( EudraCT Number )
• 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

• Plan to Share IPD: No

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: September 2023