Locally Advanced (Unresectable) or Metastatic Solid Tumors
Conditions
Keywords
ENPP1, ENPP1 inhibitor, TXN10128, TxinnoBio, Txinno Bioscience, Innate immune, STING pathway
Brief summary
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.
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).
Interventions
DRUGTXN10128
TXN10128: Oral administration once daily everyday
DRUGIrinotecan
Intravenous (IV) administration at 150 mg/m2 twice (Day 1 and Day 15) at intervals of 2 weeks in one cycle
DRUGPaclitaxel
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)
Sponsors
Txinno Bioscience Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT | 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 | A DLT is defined as any of the following AEs (graded using NCI CTCAE v5.0) whose relationship to TXN10128 cannot be ruled out. |
| Adverse events (AE) | Up to 30 days from end of treatment | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC last | Up to 21 days from Day 1 dose | The area under the concentration (AUC) -time curve calculated to the last quantifiable concentration point (mass\* time/volume) |
| Tmax | Up to 21 days from Day 1 dose | The time to reach the maximum observed concentration (time) |
| T1/2 | Up to 21 days from Day 1 dose | Elimination half-life, determined as 0.693/Lambda\_z (time) |
| Vss | Up to 21 days from Day 1 dose | Volume of distribution during the steady state phase (volume) |
| Cmax | Up to 21 days from Day 1 dose | The time to reach the maximum observed concentration (time) |
| 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). |
| Best overall response (BOR) | Up to 30 days from end of treatment | Best overall response will be summarized |
| AUC inf | Up to 21 days from Day 1 dose | The area under the concentration-time curve extrapolated to infinity (mass\*time/volume) |
Countries
South Korea
Contacts
Primary ContactEun-Young Kwak, Ph.D.
Outcome results
None listed