About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
Trial design
Sequential
Treatments tested in this trial
JZP815
DrugJZP815 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.
Treatment groups
Trial outcomes
Primary outcomes
Number of Participants With Dose-Limiting Toxicities (Part A)
Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events (Part A and B)
Change From Baseline in Hemoglobin (Part A and B)
Change From Baseline in Absolute Neutrophil Count (Part A and B)
Secondary outcomes
Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) Levels of JZP815 and its Metabolites (Part A)
Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of JZP815 and its Metabolites (Part A)
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.
Pharmacokinetic Parameter Apparent Terminal Elimination Half-life (t1/2) of JZP815 and its Metabolites (Part A)
Sponsors and contacts
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