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

NCT ID: NCT05557045

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 332 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-10
• Study Completion Date: 2028-04-01

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.

Detailed Description

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.

Conditions

Advanced Cancer; Metastatic Cancer; Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Exploration (Part A): JZP815

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

Group Type: EXPERIMENTAL

JZP815

Intervention Type: 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.

Expansion (Part B): JZP815

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

Group Type: EXPERIMENTAL

JZP815

Intervention Type: 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.

Interventions

JZP815

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jazz Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

SCRI HealthOne

Denver, Colorado, United States

Site Status: RECRUITING

Florida Cancer Specialists - Lake Nona

Orlando, Florida, United States

Site Status: RECRUITING

Florida Cancer Specialists - Sarasota

Sarasota, Florida, United States

Site Status: RECRUITING

University of Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status: RECRUITING

Oklahoma University

Oklahoma City, Oklahoma, United States

Site Status: RECRUITING

Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Tennessee Oncology - Nashville

Nashville, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Clinical Trial Disclosure & Transparency

Role: CONTACT

ClinicalTrialDisclosure@JazzPharma.com

215-832-3750

Other Identifiers

JZP815-101

Identifier Type: -

Identifier Source: org_study_id