Phase 1, FIH, Open-label, Nonrandomized, Multicenter Study of JZP815 in Participants With Advanced or Metastatic Solid Tumors Harboring Alterations in the MAPK Pathway

Jazz Pharmaceuticals29 个研究点分布在 1 个国家目标入组 98 人开始时间: 2022年10月10日最近更新: 2026年9月10日

适应症

干预措施

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Jazz Pharmaceuticals
入组人数: 98
试验地点: 29
主要终点: Change From Baseline in Hemoglobin (Part A and B)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Sequential
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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

排除标准

•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

研究组 & 干预措施

Dose Exploration (Part A): JZP815

Experimental

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

干预措施: JZP815 (Drug)

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).

干预措施: JZP815 (Drug)