A Study of TXN10128 in Subjects With Solid Tumors

Study Overview
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Brief Summary
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This is a phase I clinical trial to primarily evaluate the safety, tolerability, and addtionally assess pharmacokinetics, pharmacodynamics, and antitumor activity of investigational product, TXN10128. The target subjects will be consisted of patients with locally advanced (unresectable) or metastatic soild tumors.

Detailed Description
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This study is a multicenter, open-label, phase 1 study of TXN10128, an inhibitor of ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1). Patients with locally advanced (unresectable), or metastatic solid tumors that have relapsed or are refractory following the last line of treatment will be enrolled. The primary objective is evaluating the safety and tolerability of TXN10128 to determine the MTD. The secondary objective is characterizing the PK profile and evaluating preliminary antitumor activity of TXN10128. This study consists of the dose-escalation and dose-expansion part. In dose-escalation part, maximally 36 subjects can be enrolled across planned 6 dose levels. Bayesian optimal interval (BOIN) design will be employed to find the MTD. The target DLT rate for determining the MTD is 30% for this study. TXN10128 will be administered orally once daily for 21 days as a treatment cycle.

Official Title
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A Multicenter, Open-label, Phase 1 Dose Escalation and Expansion Study of TXN10128, an Inhibitor of ENPP1 in Subjects With Locally Advanced (Unresectable) or Metastatic Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: TXN10128


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects ≥19 years of age at the time of informed consent. Histologically and/or cytologically confirmed any progressive, locally advanced (unresectable), or metastatic solid tumors that have relapsed or are refractory following the last line of treatment and for which prior standard therapy has been ineffective, or standard therapy does not exist or is not considered appropriate. ECOG performance status of 0 or 1. Life expectancy of at least 12 weeks. Exclusion Criteria: Has leptomeningeal disease. Experienced a Grade ≥3 immune-related adverse events (irAE) with prior immunotherapy with the exception of non-clinically significant laboratory abnormalities. Prior organ transplantation. Known positive human immunodeficiency virus (HIV) infection.

Ages Eligible for Study
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Minimum Age: 19 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
Intervention Model: Single Group Assignment
Interventional Model Description: Bayesian optimal interval (BOIN) design will be employed to find the MTD. The target DLT rate for determining the MTD is 30% for this study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-escalation part<br>TXN10128 will be administered orally once daily for 21 days as a treatment cycle. TXN10128 will be evaluated across 6 dose levels. | Drug: TXN10128<br>* Participants receive TXN10128 capsules orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT | Bayesian optimal interval (BOIN, Liu and Yuan [2015]) design will be employed to find the MTD. The target DLT rate for determining the MTD is 30% for this study. The maximum sample size for the study is 36 and a maximum of 12 subjects can be assigned to a dose level | The first cycle (each cycle is 21 days) | 
| Adverse events (AE) | Adverse events (AE) defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0 at each dose level | Up to 30 days from end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | The time to reach the maximum observed concentration (time) | Up to 21 days from Day 1 dose | 
| AUC inf | The area under the concentration-time curve extrapolated to infinity (mass*time/volume) | Up to 21 days from Day 1 dose | 
| AUC last | The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass* time/volume) | Up to 21 days from Day 1 dose | 
| Tmax | The time to reach the maximum observed concentration (time) | Up to 21 days from Day 1 dose | 
| T1/2 | Elimination half-life, determined as 0.693/Lambda_z (time) | Up to 21 days from Day 1 dose | 
| Vss | Volume of distribution during the steady state phase (volume) | Up to 21 days from Day 1 dose | 
| Best overall response (BOR) | Best overall response will be summarized | Up to 30 days from end of treatment | 
| Progression free survival (PFS) | The survival function will be estimated using the Kaplan-Meier product limit method. Median duration, with a two-sided Brookmeyer-Crowley 90% confidence interval and Kaplan-Meier estimates of survival proportions will be provided at specified time points. | Up to 30 days from end of treatment | 
| Disease control rate (DCR) | The disease control rate is calculated as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease | Up to 30 days from end of treatment | 
| Duration of Response (DOR) | Duration of response is defined as the time from the date of the first documented response (CR or PR), to the date of first documented progression, or death due to study indication. Estimates will use Kaplan-Meier method | Up to 30 days from end of treatment | 
| Overall response rate (ORR) | Overall response rate will be summarized with accompanying 90% exact binomial confidence interval (CI). | Up to 30 days from end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ENPP1, ENPP1 inhibitor, TXN10128, TxinnoBio, Txinno Bioscicence, Innate immune, STING pathway