Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
CKAZ954A12101
- NCT ID:
NCT04237649
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| KAZ954 | | Arm A |
| PDR001 | | Arm B |
| NIR178 | | Arm C |
| NZV930 | | Arm D |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm A | Experimental | KAZ954 | |
| Arm B | Experimental | KAZ954 + PDR001 | |
| Arm C | Experimental | KAZ954 + NIR178 | |
| Arm D | Experimental | KAZ954 + NZV930 | |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Incidence of Dose Limiting Toxicities (DLTs) |
| Time Frame: | 35 days |
| Safety Issue: | |
| Description: | Dose Limiting Toxicities |
Secondary Outcome Measures
| Measure: | Overall Response Rate (ORR) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Disease Control Rate (DCR) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | per RECIST v1.1 and iRECIST |
| Measure: | Serum concentration profiles of KAZ954 as a single agent Cmax |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Serum concentration of KAZ954 in combination with PDR001 and derived PK parameters Cmax |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Serum concentration of KAZ954 in combination with NZV930 and derived PK parameters Cmax |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Serum/Plasma concentration of KAZ954 in combination with NIR178 Cmax |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Presence and titer of anti-KAZ954 antibodies |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Presence and titer of anti-PDR001 antibodies |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Presence and titer of anti-NZV930 antibodies |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Serum concentration profiles of KAZ954 as a single agent AUC |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Serum concentration profiles of KAZ954 in combination with PDR001 and derived PK parameters AUC |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Serum concentration profiles of KAZ954 incombination with NZV930 and derived PK parameters AUC |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | Serum/Plasma concentration profiles of KAZ954 in combination with NIR178 and derived PK parameters AUC |
| Time Frame: | 36 months |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Expression of PD-L1, and determination of ORR & PFS per RECIST 1.1 and iRECIST. |
Details
| Phase: | Early Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Solid Tumors
- KAZ954
- PDR001
- Spartalizumab
- NIR178
- NZV930
- Immunotherapy
- Phase I/Ib
Last Updated
July 27, 2021
