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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04237649

Collaborator

(none)

145

Enrollment

Locations

Arms

53.7

Anticipated Duration (Months)

11.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: KAZ954 Drug: PDR001 Drug: NIR178 Drug: NZV930	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

145 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group 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 :

Feb 20, 2020

Anticipated Primary Completion Date :

Aug 12, 2024

Anticipated Study Completion Date :

Aug 12, 2024

Arms and Interventions

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

Primary Outcome Measures

Incidence of Dose Limiting Toxicities (DLTs) [35 days]
Dose Limiting Toxicities
Incidence of adverse events and serious adverse events [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 [36 months]
Number of participants with at least one dose interruption or reduction during study treatment to assess tolerability.
Dose intensity of study treatment [36 months]
Dose intensity computed as the ratio of actual cumulative dose received and actual duration of exposure.

Secondary Outcome Measures

Overall Response Rate (ORR) [36 months]
Disease Control Rate (DCR) [36 months]
Progression Free Survival (PFS) [36 months]
per RECIST v1.1 and iRECIST
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 [36 months]
Expression of PD-L1, and determination of ORR & PFS per RECIST 1.1 and iRECIST.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University of California at Los Angeles	Los Angeles	California	United States	90095
2	Yale University Yale Cancer Center	New Haven	Connecticut	United States	06511
3	Northwestern University Medical School	Chicago	Illinois	United States	60611
4	Washington University School of Medicine Dept. of Siteman Cancer Center	Saint Louis	Missouri	United States	63110
5	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
6	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
7	Novartis Investigative Site	Shatin, New Territories		Hong Kong
8	Novartis Investigative Site	Milano	MI	Italy	20133
9	Novartis Investigative Site	Milano	MI	Italy	20162
10	Novartis Investigative Site	Sunto Gun	Shizuoka	Japan	411 8777
11	Novartis Investigative Site	Singapore		Singapore	119074
12	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
13	Novartis Investigative Site	Taipei		Taiwan	10002