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 as Monotherapy and Combination Therapy With Irinotecan or Paclitaxel in Locally Advanced 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.

This study includes a dose-escalation part and a dose-expansion part, and a TXN10128 monotherapy part and a TXN10128 + Irinotecan or Paclitaxel combination therapy part.

Study Overview

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

Detailed Description

This study includes a dose-escalation part and a dose-expansion part, and a TXN10128 monotherapy part and a TXN10128 + Irinotecan or Paclitaxel combination therapy part. The study includes dose-escalation and dose-expansion parts across three cohorts: TXN10128 monotherapy (Cohorts A) TXN10128 + Irinotecan (Cohorts B) and TXN10128+ Paclitaxel (Cohorts C).

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 1

Contacts and Locations

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

Study Locations

• Korea, Republic of
  • Incheon, Korea, Republic of, 21565
    • Recruiting
    • Gachon University Gil Medical Center
    • Contact: Joo-Hwan Park, MD, PhD
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
    • Contact: Min-Hee Ryu, M.D., Ph.D.
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
    • Contact: Jin Seok Ahn, MD, PhD
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National Univ. Hospital
    • Contact: Do-Youn Oh, M.D., Ph.D.
  • Chungcheongbuk-do
    • Cheonju, Chungcheongbuk-do, Korea, Republic of, 28644
      • Recruiting
      • Chungbuk National University Hospital
      • Contact: 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

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: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A-1; TXN10128 Monotherapy Dose esclation part	Drug: TXN10128; TXN10128: Oral administration once daily everyday
Experimental: Cohort B-1; Combination Therapy with TXN10128 and Irinotecan Dose esclation part	Drug: TXN10128; TXN10128: Oral administration once daily everyday; Drug: Irinotecan; Intravenous (IV) administration at 150 mg/m2 twice (Day 1 and Day 15) at intervals of 2 weeks in one cycle
Experimental: Cohort C-1; Combination therapy with TXN10128 and Paclitaxel Dose esclation part	Drug: TXN10128; TXN10128: Oral administration once daily everyday; Drug: Paclitaxel; IV administration at 80 mg/m2 three times (Day 1, Day 8, and Day 15) at intervals of 1 week in one cycle (IV administration at 90 mg/m2 for patients with breast cancer)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
DLT	A DLT is defined as any of the following AEs (graded using NCI CTCAE v5.0) whose relationship to TXN10128 cannot be ruled out.	Day 1 up to Day 21 for Cohort A(TXN10128 mono cohort) and Day 1 up to Day 28 for Cohort B,C(TXN10128 combination with Irinotecan or paclitaxel cohort) in dose escalation period

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; Principal Investigator: Joo-Hwan Park, M.D., Ph.D., eoul 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): December 31, 2025
• Study Completion (Estimated): June 30, 2026

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): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: ENPP1; ENPP1 inhibitor; TXN10128; TxinnoBio; Innate immune; STING pathway; Txinno Bioscience
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Irinotecan; Paclitaxel
• 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
• product manufactured in and exported from the U.S.: No