This phase 1 study will investigate the safety, dosing, and initial antitumor activity of JZP815 in participants with advanced or metastatic solid tumors harboring alterations in the MAPK pathway.
This first-in-human study will consist of two parts: Part A and Part B. Part A will characterize the safety and tolerability of JZP815, assess pharmacokinetics (PK) profile, and determine a recommended phase 2 dose (RP2D) to be further investigated in the Expansion phase (Part B). Part B will further investigate the RP2D determined in Part A, and assess antitumor activity in various subsets of disease (based on mutation and/or tumor type) in which the mechanism of action of JZP815 is applicable.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
98
JZP815 will be administered as oral capsules to participants BID approximately 12 hours apart, in the morning and in the evening. QD dosing may also be investigated, if supported by PK data.
Valkyrie Clinical Trials
Los Angeles, California, United States
SCRI HealthOne
Denver, Colorado, United States
Florida Cancer Specialists - Lake Nona
Orlando, Florida, United States
Florida Cancer Specialists - Sarasota
Sarasota, Florida, United States
University of Chicago
Chicago, Illinois, United States
NYU Langone Health
New York, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Oklahoma University
Oklahoma City, Oklahoma, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, United States
...and 5 more locations
Number of Participants With Dose-Limiting Toxicities (Part A)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Change From Baseline in Hemoglobin (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Change From Baseline in Absolute Neutrophil Count (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Change From Baseline in Platelets (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Change From Baseline in Hematocrit (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Change From Baseline in Aspartate Aminotransferase (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Change From Baseline in Alanine Aminotransferase (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Change From Baseline in Creatinine (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Change From Baseline in Total Bilirubin (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Change From Baseline in Heart Rate (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Change From Baseline in Blood Pressure (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Number of Participants With Dose Interruptions and Reductions (Part A and B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Objective Response Rate (as Defined by RECIST v1.1) (Part B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Duration of Response (Part B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) Levels of JZP815 and its Metabolites (Part A)
Time frame: MTD determination cohorts, Cycle 1 Days 1 and 15: predose and 0.25,0.5,1,2,3,4,6, 8 hours (hr) postdose; 24, 48 and 72 hr postdose relative to 1st dose given on Cycle 1 Day 1; Others, Cycle 1 Days 1, 15 or 22: predose and 0.25,0.5,1,2,3,4,6,8 hr postdose
Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of JZP815 and its Metabolites (Part A)
Time frame: MTD determination cohorts, Cycle 1 Days 1 and 15: predose and 0.25,0.5,1,2,3,4,6, 8 hours (hr) postdose; 24, 48 and 72 hr postdose relative to 1st dose given on Cycle 1 Day 1; Others, Cycle 1 Days 1, 15 or 22: predose and 0.25,0.5,1,2,3,4,6,8 hr postdose
Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of JZP815 and its Metabolites (Part A)
AUC from time 0 to infinity (AUCinf) and AUC during a dosing interval (AUCtau) will be assessed.
Time frame: MTD determination cohorts, Cycle 1 Days 1 and 15: predose and 0.25,0.5,1,2,3,4,6, 8 hours (hr) postdose; 24, 48 and 72 hr postdose relative to 1st dose given on Cycle 1 Day 1; Others, Cycle 1 Days 1, 15 or 22: predose and 0.25,0.5,1,2,3,4,6,8 hr postdose
Pharmacokinetic Parameter Apparent Terminal Elimination Half-life (t1/2) of JZP815 and its Metabolites (Part A)
Time frame: MTD determination cohorts, Cycle 1 Days 1 and 15: predose and 0.25,0.5,1,2,3,4,6, 8 hours (hr) postdose; 24, 48 and 72 hr postdose relative to 1st dose given on Cycle 1 Day 1; Others, Cycle 1 Days 1, 15 or 22: predose and 0.25,0.5,1,2,3,4,6,8 hr postdose
Pharmacokinetic Parameter Clearance (CL/F) of JZP815 (Part A)
Time frame: MTD determination cohorts, Cycle 1 Days 1 and 15: predose and 0.25,0.5,1,2,3,4,6, 8 hours (hr) postdose; 24, 48 and 72 hr postdose relative to 1st dose given on Cycle 1 Day 1; Others, Cycle 1 Days 1, 15 or 22: predose and 0.25,0.5,1,2,3,4,6,8 hr postdose
Pharmacokinetic Parameter Accumulation Ratio of JZP815 and its Metabolites (Part A)
Time frame: MTD determination cohorts, Cycle 1 Days 1 and 15: predose and 0.25,0.5,1,2,3,4,6, 8 hours (hr) postdose; 24, 48 and 72 hr postdose relative to 1st dose given on Cycle 1 Day 1; Others, Cycle 1 Days 1, 15 or 22: predose and 0.25,0.5,1,2,3,4,6,8 hr postdose
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Pharmacokinetic Parameter Apparent Volume of Distribution During Terminal Phase (Vz/F) of JZP815 (Part A)
Time frame: MTD determination cohorts, Cycle 1 Days 1 and 15: predose and 0.25,0.5,1,2,3,4,6, 8 hours (hr) postdose; 24, 48 and 72 hr postdose relative to 1st dose given on Cycle 1 Day 1; Others, Cycle 1 Days 1, 15 or 22: predose and 0.25,0.5,1,2,3,4,6,8 hr postdose
Pharmacokinetic Parameter Metabolite to Parent Ratio of JZP815 and its Metabolites (Part A)
Time frame: MTD determination cohorts, Cycle 1 Days 1 and 15: predose and 0.25,0.5,1,2,3,4,6, 8 hours (hr) postdose; 24, 48 and 72 hr postdose relative to 1st dose given on Cycle 1 Day 1; Others, Cycle 1 Days 1, 15 or 22: predose and 0.25,0.5,1,2,3,4,6,8 hr postdose
Objective Response Rate (as Defined by RECIST v1.1) (Part A)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Progression-free Survival (Part B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention
Overall Survival (Part B)
Time frame: Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention