A Study of TXN10128 in Subjects With Solid Tumors

Sponsor

Txinno Bioscience Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05978492

Collaborator

(none)

Enrollment

Arm

25.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a phase I clinical trial that will evaluate the safety, tolerability pharmacokinetics, pharmacodynamics and antitumor activity of TXN10128 (investigational product). The population will consist of locally advanced (unresectable) or metastatic soild tumors.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor	Drug: TXN10128	Phase 1

Detailed Description

This study 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, 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 27, 2023

Anticipated Primary Completion Date :

Mar 31, 2025

Anticipated Study Completion Date :

Aug 30, 2025

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Dose-escalation part

TXN10128 will be administered orally once daily for 21-days as a treatment cycle. TXN10128 will be evaluated across 6 dose levels.

Drug: TXN10128

Participants receive TXN10128 capsules orally once daily

Outcome Measures

Primary Outcome Measures

DLT [The first cycle (each cycle is 21 days)]
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

Secondary Outcome Measures

Cmax [Up to 30 days from end of treatment]
The time to reach the maximum observed concentration (time)
AUC inf [Up to 30 days from end of treatment]
The area under the concentration-time curve extrapolated to infinity (mass*time/volume)
AUC last [Up to 30 days from end of treatment]
The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass* time/volume)
Tmax [Up to 30 days from end of treatment]
The time to reach the maximum observed concentration (time)
T1/2 [Up to 30 days from end of treatment]
Elimination half-life, determined as 0.693/Lambda_z (time)
CL/F [Up to 30 days from end of treatment]
Apparent systemic clearance of drug from the plasma (volume x time -1)
Vz/F [Up to 30 days from end of treatment]
Apparent volume of distribution during the terminal elimination phase (volume)
Best overall response (BOR) [Up to 30 days from end of treatment]
Best overall response will be summarized
Progression free survival (PFS) [Up to 30 days from end of treatment]
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.
Disease control rate (DCR) [Up to 30 days from end of treatment]
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
Duration of Response (DOR) [Up to 30 days from end of treatment]
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
Overall response rate (ORR) [Up to 30 days from end of treatment]
Overall response rate will be summarized with accompanying 90% exact binomial confidence interval (CI).

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 19 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.