First-in-human test of ZE94-0605 for advanced solid tumors

Inclusion Criteria

Phase 1a Dose-Escalation Cohorts:

1. Age ≥18 years, with a pathologically confirmed, advanced, unresectable or metastatic solid tumor refractory to, or intolerant of, available therapies known to provide clinical benefit for the participant's condition, if available, and with measurable disease.

   Phase 1b Dose-Expansion Cohorts:
2. Age ≥18 years, with a pathologically confirmed, advanced, unresectable or metastatic solid tumor refractory to, or intolerant of, available therapies known to provide clinical benefit for the participant's condition, if available, or who has declined such therapy, with CCNE1 amplification and measurable disease.

   Common Inclusion Criteria:
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
4. Adequate end-organ function: creatinine clearance \>60 mL/min; AST and ALT \<3 × upper limit of normal (ULN); and total bilirubin \<1.5 × ULN, except for participants with Gilbert's disease.
5. Absolute neutrophil count ≥1.5 × 10\^9/L and platelets ≥100 × 10\^9/L.
6. Female participants of childbearing potential must be willing to abstain from heterosexual intercourse or use a protocol-recommended contraceptive method from signing informed consent through treatment and for 90 days after the last study-drug dose.
7. Male participants of childbearing potential having intercourse with females of childbearing potential must be willing to abstain from heterosexual intercourse or use a protocol-recommended contraceptive method from signing informed consent through treatment and for 90 days after the last study-drug dose. Male participants must refrain from sperm donation for the same period.
8. Willingness to comply with scheduled visits, drug administration, imaging, laboratory tests, other study procedures, and restrictions.

Exclusion Criteria

1. History of another malignancy, except adequately treated localized basal-cell or squamous-cell skin cancer, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease, or another cancer in complete remission without treatment for ≥2 years, or one with an anticipated 24-month life expectancy that does not require treatment confounding study assessments. Such cases must be discussed with the Sponsor Medical Monitor before screening for enrollment.
2. Known active hepatitis C, hepatitis B, or HIV infection.
3. Pregnancy or breastfeeding.
4. Concurrent participation in an investigational-drug trial with therapeutic intent or receipt of an investigational agent within 14 days or five half-lives (whichever is longer) before the first study dose; if half-life is unknown, a minimum 14-day washout is required. An investigational agent is one without an approved indication from the U.S. FDA.
5. Inability to tolerate oral medication, including symptomatic gastrointestinal disease significantly affecting gastrointestinal function, such as inflammatory bowel disease or resection of the stomach or small bowel.
6. Current use of or anticipated need for a medication or therapy prohibited under protocol Section 7.6.2 during the applicable prohibited period, including proton pump inhibitors, prohibited strong CYP3A4 inducers, and prohibited concomitant anticancer treatments; relevant use of strong CYP3A4 inhibitors requires protocol-directed review.
7. Psychological, familial, social, or geographic factors, another significant medical condition, or laboratory abnormalities that preclude informed consent or adherence, hamper compliance with treatment/follow-up, or confound interpretation.
8. Uncontrolled intercurrent illness, including symptomatic congestive heart failure, unstable angina, serious cardiac arrhythmia, New York Heart Association Class III/IV heart failure, severe uncontrolled ventricular arrhythmia, or ECG evidence of acute ischemia or active conduction-system abnormality; or comorbidities that preclude safety evaluation of ZE94-0605.
9. QT interval corrected by Fridericia (QTcF) ≥470 ms unless the participant has a pacemaker. Participants with incomplete or complete bundle branch block may participate following cardiology clearance. A pacemaker does not automatically exclude participation, but device and lead compatibility and institutional MRI safety clearance are required when MRI is necessary. If required MRI cannot be safely performed, the participant is ineligible unless the Sponsor Medical Monitor approves an alternative imaging method acceptable for central response assessment.

Note: This text is faithfully condensed for a public registry; original criterion numbering differs. The protocol places the newly prohibited medication reconciliation instruction at the end of exclusion criterion 9; keep this in investigator instructions rather than individual eligibility criteria, unless preferred by sponsor.

Note: Especially material changes: contraceptive window for women 90 days (older entry used 30 days); washout changed to longer of 14 days or 5 half-lives; PPI exclusion; newly explicit MRI/pacemaker safeguards.