A First-in-Human Study of ZE94-0605 in Patients With Advanced Solid Tumors

NCT07524140 | Recruiting Phase 1

• 1 other identifier: ZE94-0605-0001
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 3

Brief Summary

ZE94-0605 is an oral, selective cyclin-dependent kinase 2 (CDK2) inhibitor. This multicenter, open-label, first-in-human Phase 1 study will evaluate ZE94-0605 in adults with advanced, unresectable or metastatic solid tumors. Phase 1a will use sequential dose escalation to determine the maximally tolerated dose and biologically effective dose. Phase 1b will randomize participants with CCNE1 amplification, or another prospectively specified molecular feature, between two dose levels to select the recommended Phase 2 dose.

Conditions

Metastatic Solid Tumor; Advanced Solid Tumor Cancer

Keywords

ZE94-0605; Selective CDK2 inhibitor; CCNE1 amplification; Cyclin E1; First-in-human; Dose escalation; Dose optimization; Recommended Phase 2 dose; Project Optimus; Brain-penetrant CDK2 inhibitor

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose-Limiting Toxicities

  Number and percentage of participants in Phase 1a who experience a protocol-defined dose-limiting toxicity. Dose-limiting toxicities are specified hematologic or non-hematologic toxicities graded using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 6.0, that are not primarily attributable to the underlying cancer, a known disease complication, or a comorbid condition.

  Cycle 1, Day 1 through Day 28

• Maximally Tolerated Dose of ZE94-0605

  The maximally tolerated dose is the highest evaluated dose at which no more than 1 of up to 6 participants experiences a dose-limiting toxicity during Cycle 1. Dose-exposure saturation and evidence of an efficacious dose with an acceptable safety margin may also inform termination of dose escalation.

  Through completion of the Phase 1a dose-escalation portion, estimated up to approximately 24 months

• Recommended Phase 2 Dose of ZE94-0605

  The recommended Phase 2 dose will be selected following randomized evaluation of two Phase 1b expansion doses based on integrated safety, tolerability, pharmacokinetic, pharmacodynamic, and preliminary clinical-activity data.

  Through completion of the Phase 1b dose-expansion portion, estimated up to approximately 24 months

Secondary Outcomes (9)

• Number of Participants With Treatment-Emergent Adverse Events

  From first dose through 30 days after the last dose of ZE94-0605

• Overall Response Rate

  From baseline through Cycle 26 or end of treatment, up to approximately 24 months

• Duration of Response

  From first documented response through study completion, up to approximately 24 months

• Overall Survival

  From first dose through long-term follow-up and study completion, up to approximately 24 months

• Maximum Observed Plasma Concentration of ZE94-0605

  Cycle 1 Day 1 through Cycle 2 Day 2; each cycle is 28 days

Other Outcomes (3)

• Change in Plasma Circulating Tumor DNA

  Predose on Day 1 of Cycles 1, 2, 3, and 6; at scheduled response assessments; and at end of treatment, relapse, or progression

• Change From Baseline in Exploratory Biomarkers of CDK2 Inhibition

  Cycle 1 Day 1 predose, 2 hours, 8 hours, and approximately 24 hours postdose

• Association of Tumor Molecular Characteristics With Response or Resistance

  From baseline tissue collection through disease progression, up to approximately 24 months

Study Arms (8)

Phase 1a Dose Level -1: ZE94-0605 50 mg QD

EXPERIMENTAL

Optional dose-reduction cohort. Participants will receive ZE94-0605 50 mg orally once daily in the fasted state in continuous 28-day cycles. This dose level will be evaluated only if Dose Level 1 is not tolerated.

Drug: ZE94-0605

Phase 1a Dose Level 1: ZE94-0605 100 mg QD

EXPERIMENTAL

Participants will receive ZE94-0605 100 mg orally once daily in the fasted state in continuous 28-day cycles.

Drug: ZE94-0605

Phase 1a Dose Level 2: ZE94-0605 200 mg QD

EXPERIMENTAL

Participants will receive ZE94-0605 200 mg orally once daily in the fasted state in continuous 28-day cycles.

Drug: ZE94-0605

Phase 1a Dose Level 3: ZE94-0605 350 mg QD

EXPERIMENTAL

Participants will receive ZE94-0605 350 mg orally once daily in the fasted state in continuous 28-day cycles.

Drug: ZE94-0605

Phase 1a Dose Level 4: ZE94-0605 500 mg QD

EXPERIMENTAL

Participants will receive ZE94-0605 500 mg orally once daily in the fasted state in continuous 28-day cycles.

Drug: ZE94-0605

Phase 1a Dose Level 5: ZE94-0605 650 mg QD

EXPERIMENTAL

Participants will receive ZE94-0605 650 mg orally once daily in the fasted state in continuous 28-day cycles. If the maximally tolerated dose or biologically effective dose has not been identified, subsequent dose levels may increase by approximately 33% following Safety Review Committee review.

Drug: ZE94-0605

Phase 1b Expansion Dose A: ZE94-0605 at the MTD

EXPERIMENTAL

Approximately 15 participants with CCNE1 amplification, or another prospectively specified molecular or cellular feature, will be randomized to receive ZE94-0605 orally once daily at the maximally tolerated dose in the fasted state in continuous 28-day cycles.

Drug: ZE94-0605

Phase 1b Expansion Dose B: ZE94-0605 One Dose Level Below the MTD

EXPERIMENTAL

Approximately 15 participants with CCNE1 amplification, or another prospectively specified molecular or cellular feature, will be randomized to receive ZE94-0605 orally once daily at one dose level below the maximally tolerated dose in the fasted state in continuous 28-day cycles.

Drug: ZE94-0605

Interventions

ZE94-0605 DRUG

Oral capsules QD

Phase 1a Dose Level -1: ZE94-0605 50 mg QD; Phase 1a Dose Level 1: ZE94-0605 100 mg QD; Phase 1a Dose Level 2: ZE94-0605 200 mg QD; Phase 1a Dose Level 3: ZE94-0605 350 mg QD; Phase 1a Dose Level 4: ZE94-0605 500 mg QD; Phase 1a Dose Level 5: ZE94-0605 650 mg QD; Phase 1b Expansion Dose A: ZE94-0605 at the MTD; Phase 1b Expansion Dose B: ZE94-0605 One Dose Level Below the MTD

Eligibility Criteria

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

You may qualify if:

• Phase 1a Dose-Escalation Cohorts:
• Age 18 years or older with a pathologically confirmed, advanced, unresectable or metastatic solid tumor that is refractory to, or intolerant of, available existing therapy or therapies known to provide clinical benefit for the condition, if available, and with measurable disease.
• Phase 1b Dose-Expansion Cohorts:
• Age 18 years or older with a pathologically confirmed, advanced, unresectable or metastatic solid tumor that is refractory to, or intolerant of, available existing therapy or therapies known to provide clinical benefit for the condition, if available, or who has declined such therapy; presence of CCNE1 amplification; and measurable disease.
• Common Eligibility Criteria:
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Adequate end-organ function, defined as creatinine clearance greater than 60 mL/min, aspartate aminotransferase and alanine aminotransferase less than 3 times the upper limit of normal, and total bilirubin less than 1.5 times the upper limit of normal, except for participants with Gilbert's disease.
• Absolute neutrophil count at least 1.5 × 10\^9/L and platelet count at least 100 × 10\^9/L.
• Female participants of childbearing potential must be willing to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from screening throughout study treatment and for 90 days after the last dose of ZE94-0605.
• Male participants of reproductive potential who have intercourse with females of childbearing potential must be willing to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from the start of study treatment throughout study treatment and for 90 days after the last dose of ZE94-0605. Male participants must also refrain from sperm donation during this period.
• Willingness to comply with scheduled visits, the drug-administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions.

You may not qualify if:

• History of another malignancy, except adequately treated local basal cell carcinoma or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease, or another cancer that has been in complete remission without treatment for at least 2 years before enrollment or has a life expectancy of 24 months and does not require therapy that would confound interpretation of this study. Such cases must be discussed with the Medical Monitor before screening.
• Known active hepatitis C, hepatitis B, or human immunodeficiency virus infection.
• Pregnancy or breastfeeding.
• Concurrent participation in an investigational-drug trial with therapeutic intent, defined as receipt of prior study therapy within 14 days before study treatment.
• Inability to tolerate oral medication, including symptomatic disease that significantly affects gastrointestinal function, such as inflammatory bowel disease or resection of the stomach or small bowel.
• Receipt of an investigational agent for any indication within 5 half-lives of the agent. If the half-life is unknown, the participant must wait 1 week before the first dose of study treatment. An investigational agent is one for which there is no approved indication from the U.S. Food and Drug Administration.
• Psychological, familial, social, or geographic factors; another significant medical condition; or a laboratory abnormality that precludes informed consent or protocol compliance, may hamper adherence to study treatment or follow-up, or would confound interpretation of study results.
• Uncontrolled intercurrent illness, including but not limited to symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, New York Heart Association Class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction-system abnormalities. Participants with medical comorbidities that would preclude safety evaluation of ZE94-0605 must not be enrolled.
• QT interval corrected using Fridericia's formula (QTcF) greater than or equal to 470 milliseconds, unless the participant has a pacemaker. Participants with an incomplete or complete right or left bundle branch block may participate if cleared for enrollment by a cardiology evaluation.

Sponsors & Collaborators

• Eilean Therapeutics: lead

Study Sites (3)

St. George Private hospital

Kogarah, New South Wales, 2217, Australia

RECRUITING

SOCRU - Southern Oncology Clinical Research Unit

Bedford Park, South Australia, 5042, Australia

RECRUITING

Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology Uzbekistan

Tashkent, 100109, Uzbekistan

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Ekaterina Dokukina

CONTACT

+1 858 353 4108; kdokukina@eilenther.com

Study Design

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

Model Details: Phase 1a uses sequential 3+3 dose escalation. After completion of dose escalation and selection of the maximally tolerated dose, Phase 1b uses parallel randomized assignment to two expansion doses: the maximally tolerated dose and one dose level below it.

Study Record Dates

• First Submitted: March 27, 2026
• First Posted: April 13, 2026
• Study Start: June 25, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

UZ (1); AU (2)