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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: KAZ954
* Drug: PDR001
* Drug: NIR178
* Drug: NZV930


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>KAZ954 | Drug: KAZ954<br>* KAZ954 will be administered in every arm.<br>|
| Experimental: Arm B<br>KAZ954 + PDR001 | Drug: KAZ954<br>* KAZ954 will be administered in every arm.<br>Drug: PDR001<br>* KAZ954 + PDR001<br>|
| Experimental: Arm C<br>KAZ954 + NIR178 | Drug: KAZ954<br>* KAZ954 will be administered in every arm.<br>Drug: NIR178<br>* KAZ954 + NIR178<br>|
| Experimental: Arm D<br>KAZ954 + NZV930 | Drug: KAZ954<br>* KAZ954 will be administered in every arm.<br>Drug: NZV930<br>* KAZ954 + NZV930<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KAZ954, Solid Tumors, PDR001, Spartalizumab, NIR178, NZV930, Immunotherapy, Phase I/Ib