A JZP341 Study in Adult Participants With Advanced or Metastatic Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This study will assess the safety and efficacy of JZP341 in participants with advanced or metastatic solid tumors.

Detailed Description
-----------------
This is a first-in-human, open-label, multiple-dose, phase 1, multicenter, dose-finding study of single-agent JZP341 followed by a targeted expansion phase. This study will have 2 phases: Dose Finding Phase and Dose Expansion Phase. The Dose-Finding Phase will determine the recommended phase 2 dose (RP2D), assess safety and pharmacokinetics/pharmacodynamics, and explore preliminary antitumor activity of JZP341 in participants with relapsed or refractory advanced solid tumors. The Dose-Expansion Phase will evaluate clinical activity and further evaluate the safety of multiple doses of single-agent JZP341 at the RP2D in participants with relapsed or refractory colorectal adenocarcinoma.

Official Title
-----------------
Phase 1, Open-Label, Dose-Finding, and Expansion Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Activity of JZP341 in Adult Participants With Advanced or Metastatic Solid Tumors

Conditions
-----------------
Advanced Solid Tumor, Metastatic Solid Tumor

Intervention / Treatment
-----------------
* Drug: JZP341


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent form (ICF) ≥ 18 years of age at the time of signing the ICF Eastern Cooperative Oncology Group performance status of 0 to 2 Adequate bone marrow reserve Adequate coagulation function, liver/pancreas function, and renal function No clinically significant abnormalities in the levels of serum electrolytes Life expectancy >12 weeks Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 3 months after the last dose of study intervention: Refrain from donating sperm, AND either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR Must agree to use an approved contraception method A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: Woman of non-childbearing potential (WONCBP) Woman of childbearing potential (WOCBP) and using an effective contraceptive method A WOCBP must have a negative highly sensitive pregnancy test within 72 hours of the first dose of study intervention Inclusion Criteria for Dose Finding Phase Only: Have a histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumor that has progressed after prior standard therapy, been intolerant to or is ineligible for standard therapy, or has a malignancy for which there is no approved therapy considered standard of care Inclusion Criteria for Dose Expansion Phase Only: Histologically or cytologically confirmed colorectal adenocarcinoma that has progressed on or is intolerant to treatment from fluoropyrimidine, oxaliplatin, and irinotecan. Participants may have received bevacizumab, anti-epidermal growth factor receptor monoclonal antibody, or checkpoint inhibitor as appropriate. Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 criteria Exclusion Criteria: Primary central nervous system (CNS) tumor or symptomatic CNS metastases that are neurologically unstable or have required increasing doses of steroids within the 4 weeks prior to study entry to manage CNS symptoms (symptomatic brain metastases that have been adequately treated are not excluded) Any clinically significant cardiac disease defined as New York Heart Association class III or IV within the 6 months before Screening History of ≥ Grade 3 pancreatitis History of intracranial thrombosis or history of recurrent thrombosis (except for catheter-related thrombosis) Active (significant or uncontrolled) gastrointestinal bleeding Active uncontrolled infection (≥ Grade 2) at the time of enrollment HIV-positive, unless: CD4+ count ≥ 300/μL; Undetectable viral load; AND Receiving highly active antiretroviral therapy Uncontrolled infection of hepatitis B or hepatitis C or diagnosis of immunodeficiency Participants with Hepatitis B who have controlled infection are permitted. Participants with controlled infections must undergo periodic monitoring of Hepatitis B virus DNA. Participants must remain on antiviral therapy for ≥ 6 months beyond the last dose of study intervention. Pregnant (or plan to be pregnant) or lactating woman History of any severe or uncontrolled medical condition Unresolved toxicity, based on the investigator's assessment of the participant, from prior radiation, chemotherapy, or other targeted treatment, including investigational treatment, except for stable conditions ≤Grade 2 (ie, neuropathy, myalgia, fatigue, alopecia, therapy-related endocrinopathies) Prior treatment with JZP341 or any other asparaginase

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Dose Finding Phase: JZP341<br>Participants who will receive JZP341 on Day 1 and Day 15 of each 28-day cycle. | Drug: JZP341<br>* JZP341 will be administered as a single, intravenous infusion over 2 hours.<br>|
| Experimental: Dose Expansion Phase: JZP341<br>Participants who will receive JZP341 at the RP2D established in the Dose Finding Phase on Day 1 and Day 15 of each 28-day cycle. | Drug: JZP341<br>* JZP341 will be administered as a single, intravenous infusion over 2 hours.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose-Limiting Toxicities (Dose Finding Phase) |  | Baseline up to Day 28 | 
| Number of Participants With Treatment-emergent Adverse Events, by Severity (Dose Finding and Dose Expansion Phases) |  | Baseline up to 5 years | 
| Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of JZP341 (Dose Finding Phase) |  | Cycle 1 Day (Dy) 1: (pre & post-dose, 4 hour [hr], 8hr), Dys 2,3,4,8,11,15 (pre & post-dose),22,29; Cycle 2 Dy 1 (pre & post-dose, 8hr), Dys 4,8,15 (pre & post-dose), 29; Cycle 3+, Dys 1 (pre & post-dose), 4hr (Cycle 3 only), and 15 (each cycle, 28 dys) | 
| Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) Levels of JZP341 (Dose Finding Phase) |  | Cycle 1 Day (Dy) 1: (pre & post-dose, 4 hour [hr], 8hr), Dys 2,3,4,8,11,15 (pre & post-dose),22,29; Cycle 2 Dy 1 (pre & post-dose, 8hr), Dys 4,8,15 (pre & post-dose), 29; Cycle 3+, Dys 1 (pre & post-dose), 4hr (Cycle 3 only), and 15 (each cycle, 28 dys) | 
| Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of JZP341 (Dose Finding Phase) |  | Cycle 1 Day (Dy) 1: (pre & post-dose, 4 hour [hr], 8hr), Dys 2,3,4,8,11,15 (pre & post-dose),22,29; Cycle 2 Dy 1 (pre & post-dose, 8hr), Dys 4,8,15 (pre & post-dose), 29; Cycle 3+, Dys 1 (pre & post-dose), 4hr (Cycle 3 only), and 15 (each cycle, 28 dys) | 
| Pharmacokinetic Parameter Apparent Terminal Elimination Half-life (t1/2) of JZP341 (Dose Finding Phase) |  | Cycle 1 Day (Dy) 1: (pre & post-dose, 4 hour [hr], 8hr), Dys 2,3,4,8,11,15 (pre & post-dose),22,29; Cycle 2 Dy 1 (pre & post-dose, 8hr), Dys 4,8,15 (pre & post-dose), 29; Cycle 3+, Dys 1 (pre & post-dose), 4hr (Cycle 3 only), and 15 (each cycle, 28 dys) | 
| Pharmacokinetic Parameter Clearance (CL) of JZP341 (Dose Finding Phase) |  | Cycle 1 Day (Dy) 1: (pre & post-dose, 4 hour [hr], 8hr), Dys 2,3,4,8,11,15 (pre & post-dose),22,29; Cycle 2 Dy 1 (pre & post-dose, 8hr), Dys 4,8,15 (pre & post-dose), 29; Cycle 3+, Dys 1 (pre & post-dose), 4hr (Cycle 3 only), and 15 (each cycle, 28 dys) | 
| Pharmacokinetic Parameter Volume of Distribution (Vd) of JZP341 (Dose Finding Phase) |  | Cycle 1 Day (Dy) 1: (pre & post-dose, 4 hour [hr], 8hr), Dys 2,3,4,8,11,15 (pre & post-dose),22,29; Cycle 2 Dy 1 (pre & post-dose, 8hr), Dys 4,8,15 (pre & post-dose), 29; Cycle 3+, Dys 1 (pre & post-dose), 4hr (Cycle 3 only), and 15 (each cycle, 28 dys) | 
| Nadir Serum Asparaginase Activity Response Rate (Dose Finding Phase) | Nadir serum asparaginase activity (NSAA) response rate is defined as the proportion of participants achieving NSAA ≥ 0.1 U/mL at 14 days following the first dose of JZP341 administration. | Baseline up to Day 14 | 
| Disease Control Rate (Dose Expansion Phase) |  | Baseline up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Hypersensitivity Reactions, Anti-Drug Antibodies, and Neutralizing Antibodies (Dose Finding and Dose Expansion Phases) |  | Baseline up to 60 days after last dose | 
| Pharmacodynamic Parameter Change From Baseline in Plasma Glutamine Concentrations (Dose Finding and Dose Expansion Phases) |  | Cycle 1 Day (Dy) 1: (pre&post, 4 hour [hr], 8hr), Dys 2&3 (DFP), 4,8,11 (DFP), 15 (pre&post), 22 (DFP), 29; Cycle 2, Dy 1:pre&post, 8hr (DFP), Dys 4&8 (DFP), 15 pre, 15 post (DFP); Cycle 3+:Dy1 pre&post, 4 hr (Cycle 3 DFP only), 15 (each cycle, 28 days) | 
| Pharmacodynamic Parameter Change From Baseline in Plasma Asparagine Concentrations (Dose Finding and Dose Expansion Phases) |  | Cycle 1 Day (Dy) 1: (pre&post, 4 hour [hr], 8hr), Dys 2&3 (DFP), 4,8,11 (DFP), 15 (pre&post), 22 (DFP), 29; Cycle 2, Dy 1:pre&post, 8hr (DFP), Dys 4&8 (DFP), 15 pre, 15 post (DFP); Cycle 3+:Dy1 pre&post, 4 hr (Cycle 3 DFP only), 15 (each cycle, 28 days) | 
| Serum Asparaginase Activity of JZP341 (Dose Expansion Phase) |  | Cycle 1, Dose 1: predose; Cycle 1, Dose 2: predose; Cycle 2 and subsequent cycles: predose on Day 1 of each cycle and at the 60-day follow-up visit (each cycle is 28 days) | 
| Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of JZP341 (Dose Expansion Phase) |  | Cycle 1 Day 1 [pre- and post-dose, 4hour (hr), 8hr], Days 4, 8, 15 (pre- and post-dose) and 29; Cycle 2+: Days 1 (pre and post) and 15, and if last dose, Days 22 and 29 (each cycle, 28 days) | 
| Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) Levels of JZP341 (Dose Expansion Phase) |  | Cycle 1 Day 1 [pre- and post-dose, 4hour (hr), 8hr], Days 4, 8, 15 (pre- and post-dose) and 29; Cycle 2+: Days 1 (pre and post) and 15, and if last dose, Days 22 and 29 (each cycle, 28 days) | 
| Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of JZP341 (Dose Expansion Phase) |  | Cycle 1 Day 1 [pre- and post-dose, 4hour (hr), 8hr], Days 4, 8, 15 (pre- and post-dose) and 29; Cycle 2+: Days 1 (pre and post) and 15, and if last dose, Days 22 and 29 (each cycle, 28 days) | 
| Pharmacokinetic Parameter Apparent Terminal Elimination Half-life (t1/2) of JZP341 (Dose Expansion Phase) |  | Cycle 1 Day 1 [pre- and post-dose, 4hour (hr), 8hr], Days 4, 8, 15 (pre- and post-dose) and 29; Cycle 2+: Days 1 (pre and post) and 15, and if last dose, Days 22 and 29 (each cycle, 28 days) | 
| Pharmacokinetic Parameter Clearance (CL) of JZP341 (Dose Expansion Phase) |  | Cycle 1 Day 1 [pre- and post-dose, 4hour (hr), 8hr], Days 4, 8, 15 (pre- and post-dose) and 29; Cycle 2+: Days 1 (pre and post) and 15, and if last dose, Days 22 and 29 (each cycle, 28 days) | 
| Pharmacokinetic Parameter Volume of Distribution (Vd) of JZP341 (Dose Expansion Phase) |  | Cycle 1 Day 1 [pre- and post-dose, 4hour (hr), 8hr], Days 4, 8, 15 (pre- and post-dose) and 29; Cycle 2+: Days 1 (pre and post) and 15, and if last dose, Days 22 and 29 (each cycle, 28 days) | 
| Nadir Serum Asparaginase Activity Response Rate (Dose Expansion Phase) | Nadir serum asparaginase activity (NSAA) response rate is defined as the proportion of participants achieving NSAA ≥ 0.1 U/mL at 14 days following the first dose of JZP341 administration. | Baseline up to Day 14 | 
| Disease Control Rate (Dose Finding Phase) |  | Baseline up to Week 12 | 
| Objective Response Rate as Assessed By the Investigator (Dose Finding and Dose Expansion Phases) |  | Baseline and then every 6 weeks from Cycle 1 Day 1 until disease progression for 24 weeks, then every 8 weeks thereafter until disease progression, withdrawal of consent, new therapy, or death (each cycle 28 days), whichever occurs first, up to 1 year | 
| Duration of Response as Assessed By the Investigator (Dose Finding and Dose Expansion Phases) |  | Baseline and then every 6 weeks from Cycle 1 Day 1 until disease progression for 24 weeks, then every 8 weeks thereafter until disease progression, withdrawal of consent, new therapy, or death (each cycle 28 days), whichever occurs first, up to 1 year | 
| Progression-free Survival (Dose Expansion Phase) |  | Baseline and then every 6 weeks from Cycle 1 Day 1 until disease progression for 24 weeks, then every 8 weeks thereafter until disease progression, withdrawal of consent, new therapy, or death (each cycle 28 days), whichever occurs first, up to 1 year | 
| Overall Survival (Dose Expansion Phase) |  | Baseline and then every 6 weeks from Cycle 1 Day 1 until disease progression for 24 weeks, then every 8 weeks thereafter until disease progression, withdrawal of consent, new therapy, or death (each cycle 28 days), whichever occurs first, up to 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced Solid Tumor, Metastatic Solid Tumor, JZP341