A Study of TXN10128 in Subjects With Solid Tumors

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

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.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced (Unresectable) or Metastatic Solid Tumors
• Intervention / Treatment: Drug: TXN10128

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jong Heun Lee, Ph.D.; Phone Number: 82 31 778 8688; Email: jong@txinno.com
• Study Contact Backup: Name: Eun-Young Kwak, Ph.D.; Phone Number: 82 31 778 8688; Email: bella@txinno.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
    • Principal Investigator: Min-Hee Ryu, M.D., Ph.D.
    • Contact: Min-Hee Ryu, M.D., Ph.D.
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
    • Contact: Jin Seok Ahn, MD, PhD
    • Principal Investigator: Jin Seok Ahn, MD, PhD
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National Univ. Hospital
    • Principal Investigator: Do-Youn Oh, M.D., Ph.D.
    • Contact: Do-Youn Oh, M.D., Ph.D.
  • Chungcheongbuk-do
    • Cheonju, Chungcheongbuk-do, Korea, Republic of, 28644
      • Not yet recruiting
      • Chungbuk National University Hospital
      • Contact: Ki-hyeong Lee, MD, PhD
      • Principal Investigator: Ki-hyeong Lee, MD, PhD
  • Gyeonggi-do
    • Seongnam, Gyeonggi-do, Korea, Republic of, 13620
      • Recruiting
      • Seoul National University Bundang Hospital
      • Contact: SeHyun Kim, MD, PhD
      • Principal Investigator: SeHyun Kim, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-escalation part; TXN10128 will be administered orally once daily.	Drug: TXN10128; Participants receive TXN10128 capsules orally once daily.

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: Txinno Bioscience Inc.
• Investigators: Principal Investigator: Do-Youn Oh, M.D., Ph.D., Seoul National University Hospital; Principal Investigator: Min-Hee Ryu, M.D., Ph.D., Asan Medical Center; Principal Investigator: Jin Seok Ahn, M.D., Ph.D., Samsung Medical Center; Principal Investigator: SeHyun Kim, M.D., Ph.D., Seoul National University Bundang Hospital; Principal Investigator: Ki-hyeong Lee, M.D., Ph.D., Chungbuk National University Hospital

Publications and helpful links

Helpful Links

• Homepage of Txinno Bioscience

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2023
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): August 30, 2025

Study Registration Dates

• First Submitted: July 20, 2023
• First Submitted That Met QC Criteria: July 29, 2023
• First Posted (Actual): August 7, 2023

Study Record Updates

• Last Update Posted (Actual): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: ENPP1; ENPP1 inhibitor; TXN10128; TxinnoBio; Innate immune; STING pathway; Txinno Bioscience
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TXN10128-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No