A Study of JZP815 Oral Capsules in Adult Participants With Advanced or Metastatic Solid Tumors Harboring Mitogen Activated Protein Kinase (MAPK) Pathway Alterations to Investigate the Safety, Dosing, and Antitumor Activity of JZP815

NCT05557045 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: JZP815-101
• Study Type: interventional
• Target: 332
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Solid Tumor; Advanced Cancer; Metastatic Cancer

Keywords

Advanced Cancer; Metastatic Cancer; Solid Tumor; JZP815

Outcome Measures

Primary Outcomes (15)

• Number of Participants With Dose-Limiting Toxicities (Part A)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  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)

  Baseline until death, withdrawal of consent, or lost to follow-up, up to 18 months after last participant starts study intervention

Secondary Outcomes (11)

• Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) Levels of JZP815 and its Metabolites (Part A)

  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)

  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)

  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)

  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)

  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

Study Arms (2)

Dose Exploration (Part A): JZP815

EXPERIMENTAL

Participants will receive JZP815 with a starting dose of 20 mg twice daily (BID).

Drug: JZP815

Expansion (Part B): JZP815

EXPERIMENTAL

Participants with advanced or metastatic solid tumors who will receive JZP815 at the RP2D established in Dose Exploration (Part A).

Drug: JZP815

Interventions

JZP815 DRUG

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.

Dose Exploration (Part A): JZP815; Expansion (Part B): JZP815

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥ 18 years of age, at the time of signing the informed consent
• Participants who have histological or cytological diagnosis of an advanced or metastatic solid tumor carrying a documented, clinically significant, MAPK pathway alteration
• Participants must have exhausted all available standard of care therapies, or in the opinion of the investigator would be unlikely to tolerate or derive clinically meaningful benefit from available standard of care therapy
• Performance status (ECOG) of 0 or 1, measured within 72 hours before start of treatment. For Arm 7 (NRAS Q61 mutated anaplastic thyroid cancer) in Part B (Expansion), ECOG of 0 to 2, measured within 72 hours before the start of treatment.
• Must have measurable disease by RECIST v1.1
• Tumor must be safely amenable to core needle or excisional biopsy (applies only to participants enrolled in Pre-Expansion cohorts)
• Adequate organ function
• Expected life expectancy of at least 12 weeks
• For each arm in Part B (Expansion), participants must be diagnosed with the tumor type(s) carrying the mutation(s) specified and meet protocol specified requirements for prior therapy
• Male participants must agree to refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception
• Female participants are eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: is a women of nonchildbearing potential (WONCBP) or is a women of childbearing potential (WOCBP) and using a contraceptive method that is highly effective during the study intervention period and for at least 3 months after the last dose of study intervention and agrees not to donate eggs
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 3 days before the first dose of study intervention
• Capable of giving signed informed consent

You may not qualify if:

• Known uncontrolled brain metastases. Stable brain metastases either treated or being treated with a stable dose of steroids/anticonvulsants, with no dose change in the previous 4 weeks, are permitted
• Active fungal, bacterial and/or known viral infection including HIV or Hepatitis A, B, C
• Concomitant malignancies or previous malignancies with less than 2 years disease-free interval at the time of enrollment, with the exception of non-metastatic, non-melanomatous skin cancers, carcinoma in-situ, melanoma in-situ, prostate cancer with undetectable PSA, indolent thyroid cancer that are adequately treated
• Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (\> New York Heart Association Classification Class II), QTc ≥ 470 msec, or serious cardiac arrhythmia requiring medication
• Uncontrolled or severe intercurrent medical condition
• Gastrointestinal condition that could impair absorption of study intervention or inability to ingest study intervention
• In the judgement of the investigator, any important medical illness or abnormal laboratory finding that would increase the risk of participating in this study
• Received any cancer directed therapy (chemotherapy, hormonal therapy, biologic, etc.) within 28 days or 5 half-lives (whichever is shorter) of starting study intervention. For Arm 7 (NRAS Q61 mutated anaplastic thyroid cancer) in Part B (Expansion), participants who have received radio-sensitizing chemotherapy (low-dose chemotherapy) are permitted a wash-out period of 7 days or 5 half-lives, whichever is shorter (a discussion with the sponsor is required). Participants who have received radiotherapy must have recovered from acute toxicities associated with treatment.
• Use of any products or medicines known to be strong or moderate inducers or inhibitors of CYP3A4, which cannot be discontinued at least 4 weeks or 5 half-lives (whichever is shorter) before starting study intervention, or planned use at any time during the study
• Use of proton pump inhibitors (eg, omeprazole) and histamine-2 receptor antagonists (eg, famotidine), which cannot be discontinued at least 2 weeks before first dose, or planned use at any time during the study
• Concurrent therapy with any other investigational agent

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (15)

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

RECRUITING

SCRI HealthOne

Denver, Colorado, 80218, United States

RECRUITING

Florida Cancer Specialists - Lake Nona

Orlando, Florida, 32827, United States

RECRUITING

Florida Cancer Specialists - Sarasota

Sarasota, Florida, 34232, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Oklahoma University

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Tennessee Oncology - Nashville

Nashville, Tennessee, 37203, United States

RECRUITING

Texas Oncology- Central South

Austin, Texas, 78731, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Texas Oncology- Gulf Coast

The Woodlands, Texas, 77380, United States

RECRUITING

Virginica Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Clinical Trial Disclosure & Transparency

CONTACT

215-832-3750; ClinicalTrialDisclosure@JazzPharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2022
• First Posted: September 27, 2022
• Study Start: October 10, 2022
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)