First in Human Study of UCT-01-097 in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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This first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of UCT-01-097 in patients with advanced solid tumors.

Official Title
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A Phase 1, First in Human, Dose-Escalation Study of UCT-01-097 in Participants With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: UCT-01-097
* Drug: Gemcitabine
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced solid tumor Measurable disease, per RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Adequate organ function Exclusion Criteria: Has not recovered [recovery is defined as NCI CTCAE, version 5.0, grade ≤1] from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements Received prior chemotherapeutic, investigational, or other therapies for the treatment of cancer within 14 days with small molecule and within 28 days with biologic before the first dose of UCT-01-097 Progressive or symptomatic brain metastases Serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection History of phosphate or calcium disorder History of significant cardiac disease History or current evidence/risk of retinopathy History of myelodysplastic syndrome (MDS) or AML History of another cancer within 3 years before Day 1 of study treatment, with the exception of basal or squamous cell carcinoma of the skin that has been definitively treated. A history of other malignancies with a low risk of recurrence, including appropriately treated ductal carcinoma in situ (DCIS) of the breast and prostate cancer with a Gleason score less than or equal to 6, are also not excluded If female, is pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Finding as Monotherapy - Part 1<br> | Drug: UCT-01-097<br>* Orally available kinase inhibitor<br>|
| Experimental: Expansion as Monotherapy - Part 2<br> | Drug: UCT-01-097<br>* Orally available kinase inhibitor<br>|
| Experimental: Dose Finding in Combination - Part 3<br> | Drug: UCT-01-097<br>* Orally available kinase inhibitor<br>Drug: Gemcitabine<br>* Gemcitabine injection for intravenous use.<br>* Other names: Gemzar;Drug: Paclitaxel<br>* Paclitaxel protein-bound particles for injectable suspension (albumin-bound).<br>* Other names: Abraxane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events and serious adverse events | Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE Version 5.0 | up to 2 years | 
| Maximum Tolerated Dose (MTD) | Highest administered dose with < 33% participants experiencing dose limiting toxicity (DLT) in the first 6 DLT evaluable participants | 28 Days | 
| Recommended Phase 2 Dose (RP2D) | Based on the maximum tolerated dose, cumulative safety, and pharmacokinetic data | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma UCT-01-097 Concentration (Cmax) | PK assessment for UCT-01-097 | Day 1 | 
| Maximum Plasma UCT-01-097 Concentration at steady state (Cmax,ss) | PK assessment for UCT-01-097 | Day 15 | 
| UCT-01-097 Trough Plasma Concentration (Cmin) | PK assessment for UCT-01-097 | Day 1 | 
| UCT-01-097 Trough Plasma Concentration at Steady State (Cmin,ss) | PK assessment for UCT-01-097 | Day 15 | 
| Time of Maximum Plasma UCT-01-097 Concentration (Tmax) | PK assessment for UCT-01-097 | Cycle 1 (each cycle is 28 days) | 
| Area Under the Plasma Concentration-Time Curve Over Dosing Interval (AUCtau) of UCT-01-097 | PK assessment for UCT-01-097 | Day 15 | 
| Apparent Clearance (CL/F) of UCT-01-097 | PK assessment for UCT-01-097 | Cycle 1 (each cycle is 28 days) | 
| Apparent Volume of Distribution (Vz/F) of UCT-01-097 | PK assessment for UCT-01-097 | Cycle 1 (each cycle is 28 days) | 
| Accumulation Ratio (Rac) of UCT-01-097 | PK assessment for UCT-01-097 | Cycle 1 (each cycle is 28 days) | 
| Terminal Half-life (t1/2) of UCT-01-097 | PK assessment for UCT-01-097 | Cycle 1 (each cycle is 28 days) | 
| Objective Response Rate (ORR) | Percentage of participants with best response of CR or PR according to RECIST 1.1 | up to 2 years | 
| Time to Response (TTR) | Time from start of treatment to complete response or partial response | up to 2 years | 
| Duration of Response (DOR) | Time from complete response or partial response to objective disease progression or death due to any cause | up to 2 years | 
| Progression Free Survival (PFS) | PFS is defined as the time from the start of the treatment until objective disease progression or death from any cause | up to 2 years | 
| 1 Year Overall Survival (1YOS) | Proportion of participants alive at 1 year from the start of treatment to death from any cause | 1 year | 
| 2 Year Overall Survival (2YOS) | Proportion of participants alive at 2 years from the start of treatment to death from any cause | 2 years |