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A Phase I/Ib, Study of KAZ954 as a Single Agent and in Combination With Spartalizumab, NZV930 and NIR178 in Patients With Advanced Solid Tumors

Phase 1
Completed
Conditions
Solid Tumors
Registration Number
JPRN-jRCT2080225114
Lead Sponsor
ovartis Pharma. K.K.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
completed
Sex
All
Target Recruitment
145
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 & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
- Incidence of Dose Limiting Toxicities (DLTs)<br>- Incidence of adverse events and serious adverse events<br>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.<br>- Number of participants with dose interruptions and dose reductions<br>Number of participants with at least one dose interruption or reduction during study treatment to assess tolerability.<br>- Dose intensity of study treatment <br>Dose intensity computed as the ratio of actual cumulative dose received and actual duration of exposure.
Secondary Outcome Measures
NameTimeMethod
- Overall Response Rate (ORR)<br>- Disease Control Rate (DCR)<br>- Progression Free Survival (PFS)per RECIST v1.1 and iRECIST<br>- Serum concentration profiles of KAZ954 as a single agent Cmax <br>- Serum concentration of KAZ954 in combination with PDR001 and derived PK parameters Cmax <br>- Serum concentration of KAZ954 in combination with NZV930 and derived PK parameters Cmax <br>- Serum/Plasma concentration of KAZ954 in combination with NIR178 Cmax <br>- Presence and titer of anti-KAZ954 antibodies <br>- Presence and titer of anti-PDR001 antibodies<br>- Presence and titer of anti-NZV930 antibodies <br>- 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 NZV930Expression of PD-L1, and determination of ORR & PFS per RECIST 1.1 and iRECIST.
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