A Phase 1, First-in-human, Open-label, Multicenter Study of JZP898 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- JZP898
- Conditions
- Advanced Solid Tumor
- Sponsor
- Jazz Pharmaceuticals
- Enrollment
- 177
- Locations
- 9
- Primary Endpoint
- Number of Participants with Dose Limiting Toxicities in Monotherapy and Combination Therapy
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This Phase 1 first-in-human study will investigate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of JZP898 monotherapy as well as JZP898 in combination with pembrolizumab in adult participants with advanced or metastatic solid tumors.
Detailed Description
Two-part study: Part A Dose Exploration (Parts A1 and A2) and Part B Combination Expansion. Part A Dose Exploration: * Part A1 - a monotherapy dose exploration to determine the monotherapy recommended dose and/or maximum tolerated dose (MTD) (or highest cleared dose level) and safety profile of JZP898. * Part A2 - a combination dose exploration of JZP898 plus pembrolizumab to determine the CombiRD (combination recommended dose for expansion). Part B Combination Expansion: * Part B - combination expansion using a basket design to evaluate clinical antitumor activity and safety profile of JZP898 in combination with pembrolizumab at the CombiRD identified in Part A2.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Part A1 Dose Exploration: JZP898 monotherapy
Intervention: JZP898
Part A2 Dose Exploration: JZP898 in combination with pembrolizumab
Intervention: JZP898
Part A2 Dose Exploration: JZP898 in combination with pembrolizumab
Intervention: Pembrolizumab
Part B Combination Expansion: JZP898 in combination with pembrolizumab
Intervention: JZP898
Part B Combination Expansion: JZP898 in combination with pembrolizumab
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Number of Participants with Dose Limiting Toxicities in Monotherapy and Combination Therapy
Time Frame: Up to 36 months
Incidence of TEAEs and SAEs in Monotherapy and Combination Therapy
Time Frame: Up to 36 months
Incidence of dose interruptions, discontinuation, and reductions due to TEAEs in Monotherapy and Combination Therapy
Time Frame: Up to 36 months
Objective Response Rate (ORR) As Assessed by the Investigator In Combination Therapy
Time Frame: Up to 36 months
Secondary Outcomes
- Pharmacokinetic Parameter: Maximum Concentration (Cmax) of JZP898 in Monotherapy and Combination Therapy(Up to 36 months)
- Pharmacokinetic Parameter: Time to Maximum Concentration (Tmax) of JZP898 in Monotherapy and Combination Therapy(Up to 36 months)
- Pharmacokinetic Parameter: Terminal Elimination Half-life (t½) of JZP898 in Monotherapy and Combination Therapy(Up to 36 months)
- Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of JZP898 in Monotherapy and Combination Therapy(Up to 36 months)
- Pharmacokinetic Parameter: Clearance (CL) of JZP898 in Monotherapy and Combination Therapy(Up to 36 months)
- Pharmacokinetic Parameter: Volume of Distribution (V) of JZP898 in Monotherapy and Combination Therapy(Up to 36 months)
- Pharmacokinetic Parameter: Activated IFNα-to-JZP898 Ratio in Monotherapy and Combination Therapy(Up to 36 months)
- Pharmacokinetic Parameter: Accumulation ratio for Cmax in Monotherapy and Combination Therapy(Up to 36 months)
- Pharmacokinetic Parameter: Accumulation Ratio for AUC in Monotherapy and Combination Therapy(Up to 36 months)
- ORR As Assessed by the Investigator in Monotherapy(Up to 36 months)
- Duration of Response (DoR) As Assessed by the Investigator(Up to 36 months)
- Disease Control Rate (DCR) As Assessed by the Investigator(Up to 36 months)
- Progression-free Survival (PFS) As Assessed by the Investigator(Up to 36 months)
- Overall Survival (OS)(Up to 36 months)
- Incidence of ADAs towards JZP898(Up to 36 months)