Clinical trial NCT04237649: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Solid Tumors
Keywords: Solid Tumors
KAZ954
PDR001
Spartalizumab
NIR178
NZV930
Immunotherapy
Phase I/Ib
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-01-23
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs)
timeFrame: Up to 35 days
measure: Incidence of adverse events and serious adverse events during the on-treatment period
timeFrame: Up to approximately 52 weeks (KAZ954 single agent), 20 weeks (KAZ954+PDR001) and 24 weeks (KAZ954+NIR178)
measure: Number of participants with dose interruptions and dose reductions
timeFrame: Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178)
measure: Dose intensity of study treatment
timeFrame: Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178)
Secondary outcomes:
measure: Overall Response Rate (ORR) per RECIST v1.1
timeFrame: Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178)
measure: Overall Response Rate (ORR) per iRECIST
timeFrame: Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178)
measure: Disease Control Rate (DCR) per RECIST v1.1
timeFrame: Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178)
measure: Disease Control Rate (DCR) per iRECIST
timeFrame: Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178)
measure: Progression-Free Survival (PFS) per RECIST v1.1
timeFrame: Up to approximately 52 weeks (KAZ954 single agent), 20 weeks (KAZ954+PDR001) and 24 weeks (KAZ954+NIR178)
measure: Progression-Free Survival (iPFS) per iRECIST
timeFrame: Up to approximately 52 weeks (KAZ954 single agent), 20 weeks (KAZ954+PDR001) and 24 weeks (KAZ954+NIR178)
measure: Maximum observed serum concentration (Cmax) of KAZ954
timeFrame: Cycle 1 Day 1 (C1D1) and Cycle 3 Day 1 (C3D1): pre-dose, 1, 24, 72, 168, 240 and 360 hours after the end of the infusion. The duration of the infusion was 2 hours. One cycle=28 days
measure: Maximum observed serum concentration (Cmax) of PDR001
timeFrame: Cycle 1 Day 1 (C1D1) and Cycle 3 Day 1 (C3D1): pre-dose, 1, 168, 336 and 672 hours after the end of the infusion. The duration of the infusion was 30 minutes. One cycle=28 days
measure: Maximum observed plasma concentration (Cmax) of NIR178 and its metabolite NJI765
timeFrame: Cycle 1 Day 1 (C1D1) and Cycle 2 Day 1 (C2D1): pre-dose, 15 minutes, 1, 2, 4 and 6 hours after morning dose and 12 hours after evening dose. One cycle=28 days
measure: Area under the serum concentration-time curve from time zero to 14 days post dose (AUC0-14d) of KAZ954
timeFrame: Cycle 1 Day 1 (C1D1) and Cycle 3 Day 1 (C3D1): pre-dose, 1, 24, 72, 168, 240 and 360 hours after the end of the infusion. The duration of the infusion was 2 hours. One cycle=28 days
measure: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of PDR001
timeFrame: Cycle 1 Day 1 (C1D1) and Cycle 3 Day 1 (C3D1): pre-dose, 1, 168, 336 and 672 hours after the end of the infusion. The duration of the infusion was 30 minutes. One cycle=28 days
measure: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of NIR178 and its metabolite NJI765
timeFrame: Cycle 1 Day 1 (C1D1) and Cycle 2 Day 1 (C2D1): pre-dose, 15 minutes, 1, 2, 4 and 6 hours after morning dose and 12 hours after evening dose. One cycle=28 days
measure: Number of participants with anti-KAZ954 antibodies
timeFrame: Baseline (before first dose) and post-baseline (assessed throughout the treatment, up to approximately 48 weeks, 16 weeks and 20 weeks for KAZ954 single agent, KAZ954+PDR001 and KAZ954+NIR178, respectively)
measure: Number of participants with anti-PDR001 antibodies
timeFrame: Baseline (before first dose) and post-baseline (assessed throughout the treatment, up to approximately 16 weeks)
measure: Overall Response Rate (ORR) using RECIST v1.1 and iRECIST by PD-L1 expression
timeFrame: Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178)
measure: Progression Free Survival (PFS) using RECIST v1.1 and iRECIST by PD-L1 expression
timeFrame: Up to approximately 52 weeks (KAZ954 single agent), 20 weeks (KAZ954+PDR001) and 24 weeks (KAZ954+NIR178)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University Of California LA
state: California
city: New Haven
country: United States
facility: Yale University Yale Cancer Center
state: Connecticut
city: Chicago
country: United States
facility: Northwestern University Med School
state: Illinois
city: Saint Louis
country: United States
facility: WA Uni School Of Med Dept. of Siteman Cancer Center
state: Missouri
city: Houston
country: United States
facility: Uni of TX MD Anderson Cancer Cntr
state: Texas
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Shatin New Territories
country: Hong Kong
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Sunto Gun
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: