JZP898 Intravenous Infusion as Monotherapy and Combination With Pembrolizumab in Adults With Advanced/Metastatic Solid Tumors

Study Overview
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Brief Summary
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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
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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) and safety profile of JZP898. Part A2 - a combination dose exploration of JZP898 plus pembrolizumab to determine the combination recommended dose followed by confirmation of the recommended phase 2 dose (Combination RP2D) 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 Combination RP2D identified in Part A2.

Official Title
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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

Conditions
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Advanced Solid Tumor, Metastatic Solid Tumor

Intervention / Treatment
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* Drug: JZP898
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Adult ≥ 18 years of age Histological or cytological diagnosis of advanced or metastatic solid tumor. a. Previously treated participants with solid tumors (NSCLC, melanoma, HNSCC, RCC, HCC, gastroesophageal carcinomas, UC, or CRC [MSI-H]) for whom, in the opinion of the investigator, there is no SoC available to convey clinical benefit. Participants in select tumor types: NSCLC: eligible for platinum-based therapy and received platinum-based therapy prior to inclusion in the study. HNSCC: eligible for platinum therapy and received platinum-based therapy prior to inclusion in this study. Melanoma with known BRAFv600 mutation: received BRAF/MEKi therapy before this study. ECOG score of 0 to 1. Measurable disease per RECIST v1.1 criteria. Parts A1 and A2 only: willing to consent to mandatory tumor biopsies (both pretreatment and post-treatment with JZP898) unless medically infeasible Adequate organ and bone marrow function as indicated by the following laboratory values (within 4 weeks prior to starting the study interventions) Men and women of reproductive potential to observe highly effective birth control for the duration of treatment and for 4 months following the last dose of study drug; Additional criteria may apply Exclusion Criteria Unresolved toxicities > Grade 1. Hypersensitivity to mAb, IFNα, or study intervention components. Primary CNS tumor or symptomatic CNS metastases. Have a second primary malignancy treated within the previous 2 years (exceptions: non-metastatic, non-melanomatous skin cancers, carcinoma in-situ, and melanoma in-situ). Active autoimmune disease (in the last 2 years) requiring systemic steroids or immunosuppressive agents. Active or history of pneumonitis or interstitial lung disease requiring steroid treatment. Any history of suicidal behavior or any suicidal ideation Clinically significant ischemic/hemorrhagic cerebrovascular accident/stroke and/or clinically significant active cardiovascular disease Received any anticancer therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug Received prior radiotherapy within 2 weeks of the first dose of study drug Major surgery within 2 weeks prior to the first dose of study intervention. Participant is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study Had an allogeneic tissue/solid organ transplant. Receipt of prior IFNα therapy

Ages Eligible for Study
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Minimum Age: 18 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: Part A1 Dose Exploration: JZP898 monotherapy<br> | Drug: JZP898<br>* Investigational drug monotherapy<br>|
| Experimental: Part A2 Dose Exploration: JZP898 in combination with pembrolizumab<br> | Drug: JZP898<br>* Investigational drug monotherapy<br>Drug: Pembrolizumab<br>* Approved anti-PD1 antibody<br>|
| Experimental: Part B Combination Expansion: JZP898 in combination with pembrolizumab<br> | Drug: JZP898<br>* Investigational drug monotherapy<br>Drug: Pembrolizumab<br>* Approved anti-PD1 antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicities |  | Up to 36 months | 
| Incidence of TEAEs and SAEs |  | Up to 36 months | 
| Incidence of dose interruptions, discontinuation, and reductions due to TEAEs |  | Up to 36 months | 
| Objective Response Rate (ORR) As Assessed by the Investigator |  | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameter: Maximum Concentration (Cmax) of JZP898 |  | Up to 36 months | 
| Pharmacokinetic Parameter: Time to Maximum Concentration (Tmax) of JZP898 |  | Up to 36 months | 
| Pharmacokinetic Parameter: Terminal Elimination Half-life (t½) of JZP898 |  | Up to 36 months | 
| Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of JZP898 |  | Up to 36 months | 
| Pharmacokinetic Parameter: Clearance (CL) of JZP898 |  | Up to 36 months | 
| Pharmacokinetic Parameter: Volume of Distribution (V) of JZP898 |  | Up to 36 months | 
| Pharmacokinetic Parameter: Activated IFNα-to-JZP898 Ratio |  | Up to 36 months | 
| Mean Dose Proportionality of JZP898 and Activated IFNα |  | Up to 36 months | 
| Pharmacokinetic Parameter: Accumulation ratio for Cmax |  | Up to 36 months | 
| Pharmacokinetic Parameter: Accumulation Ratio for AUC |  | Up to 36 months | 
| Mean JZP898 and Activated IFNα Concentrations |  | Up to 36 months | 
| ORR As Assessed by the Investigator |  | 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 | 
| Changes in tumor immune cell profile in response to monotherapy and combination therapy as measured by gene expression (nanoString) |  | Up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid Tumor, Metastatic Solid Tumor, JZP898