A First-in-Human Study of ZE94-0605 in Patients With Advanced Solid Tumors
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorEilean Therapeutics
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
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.
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.
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
ZE94-0605
DrugOral capsules QD
Treatment groups
60 Participants
are divided into 8 treatment groups8
Treatment groupsSee each treatment group below.
Group A: Phase 1a Dose Level -1: ZE94-0605 50 mg QDExperimental treatment 1 intervention
Group B: Phase 1a Dose Level 1: ZE94-0605 100 mg QDExperimental treatment 1 intervention
Group C: Phase 1a Dose Level 2: ZE94-0605 200 mg QDExperimental treatment 1 intervention
Group D: Phase 1a Dose Level 3: ZE94-0605 350 mg QDExperimental treatment 1 intervention
Group E: Phase 1a Dose Level 4: ZE94-0605 500 mg QDExperimental treatment 1 intervention
Group F: Phase 1a Dose Level 5: ZE94-0605 650 mg QDExperimental treatment 1 intervention
Group G: Phase 1b Expansion Dose A: ZE94-0605 at the MTDExperimental treatment 1 intervention
Group H: Phase 1b Expansion Dose B: ZE94-0605 One Dose Level Below the MTDExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Cycle 1, Day 1 through Day 282
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.
Time frame
Through completion of the Phase 1a dose-escalation portion, estimated up to approximately 24 months3
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.
Time frame
Through completion of the Phase 1b dose-expansion portion, estimated up to approximately 24 monthsSecondary outcomes
1
Number of Participants With Treatment-Emergent Adverse Events
Number and percentage of participants with treatment-emergent adverse events, serious adverse events, and adverse events leading to dose modification, treatment discontinuation, or death. Severity will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 6.0.
Time frame
From first dose through 30 days after the last dose of ZE94-06052
Overall Response Rate
The proportion of evaluable participants whose best overall response is complete response or partial response, assessed using Response Evaluation Criteria in Solid Tumors, Version 1.1, or other disease-appropriate response criteria specified for the participant. Results will be summarized by tumor type and CCNE1 amplification status.
Time frame
From baseline through Cycle 26 or end of treatment, up to approximately 24 months3
Duration of Response
Among participants with a complete or partial response, duration of response is the time from the first documented response until documented disease progression or death from any cause, whichever occurs first. Results will be summarized by CCNE1 amplification status.
Time frame
From first documented response through study completion, up to approximately 24 months4
Overall Survival
Overall survival is the time from the first dose of ZE94-0605 until death from any cause.
Time frame
From first dose through long-term follow-up and study completion, up to approximately 24 monthsOther outcomes
1
Change in Plasma Circulating Tumor DNA
Plasma circulating tumor DNA will be evaluated by research next-generation sequencing to assess molecular response dynamics and potential mechanisms of resistance.
Time frame
Predose on Day 1 of Cycles 1, 2, 3, and 6; at scheduled response assessments; and at end of treatment, relapse, or progression2
Change From Baseline in Exploratory Biomarkers of CDK2 Inhibition
Alternative exploratory biomarkers of CDK2 pathway inhibition may be evaluated ex vivo using plasma samples to refine and validate surrogate measures of target activity.
Time frame
Cycle 1 Day 1 predose, 2 hours, 8 hours, and approximately 24 hours postdose3
Association of Tumor Molecular Characteristics With Response or Resistance
Archived or newly obtained tumor tissue may be evaluated by next-generation sequencing and other exploratory analyses to assess molecular features associated with response to, or resistance to, ZE94-0605 and to support potential companion-diagnostic development.
Time frame
From baseline tissue collection through disease progression, up to approximately 24 monthsSponsors and contacts
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Source ClinicalTrials.gov