Phase 1/2 Trial of TTX-MC138 Doses First Patient in Cohort 4
The fourth cohort of an ongoing phase 1/2 has dosed its first patient with TTX-MC138 in advanced solid tumors.
DNA research concept: © catalin - stock.adobe.com
The first patient with an advanced solid tumor has been dosed in the fourth cohort of the phase 1/2 trial (NCT06260774) evaluating the safety and tolerability of TTX-MC138, a first-in-class therapeutic candidate targeting microRNA-10b.1
The dose in this cohort, which was officially launched earlier this month,2 is approximately 50% higher than in cohort 3, per protocol, with no dose-limiting toxicities (DLTs) or significant safety signals reported to date.1
Of the 10 patients treated across the first 4 cohorts, 7 remain on study without DLTs or disease progression. The Safety Review Committee (SRC) has approved both the initiation of cohort 4 and additional enrollment in cohort 3 to further characterize safety. Preliminary pharmacokinetic (PK) and pharmacodynamic (PD) data from cohorts 1 through 3 align with preclinical and phase 0 (NCT05908773) findings, supporting TTX-MC138’s mechanistic profile.
"Commencement of treatment in cohort 4 has been our vision for evaluating the potential of TTX-MC138 at multiple dose levels. Cohort 4 builds upon our safety, PK/PD and exploratory data and is an important element of our clinical development strategy. We believe this milestone will inform the dose expansion stage of the clinical trial and may allow us to obtain initial evidence of clinical activity as the program continues to advance," said Sue Duggan, TransCode's senior vice president of operations, in a press release.1 "Enrollment into the study continues based on the cumulative safety data review. Additional cohort 4 patients are scheduled for treatment in cohort 4 for treatment with TTX-MC138 while preliminary data analysis continues."
About the Phase 1/2 Study of TTX-MC138
The multicenter, open-label, dose-escalation and dose-expansion employs a 28-day cycle with intravenous TTX-MC138 administered on day 1.3 Dose-escalation has progressed from 0.4 mg/kg (cohort 1) to 3.2 mg/kg (cohort 3), with cohort 4 exploring higher doses.
Preliminary PK analysis suggests the 0.8 to 1.6 mg/kg range (cohorts 1-2) may be efficacious. Eligible patients have refractory/metastatic solid tumors, measurable disease per RECIST v1.1 criteria, an ECOG performance status between 0 and 2, and adequate organ function.
Primary end points include safety, tolerability, and overall response rate, including complete and partial response or stable disease ≥8 weeks per RECIST v1.1.
Enrollment continues based on favorable safety data, with additional Cohort 4 patients scheduled for treatment.1 The safety review committee unanimously endorsed cohort 4 initiation and cohort 3 expansion after reviewing safety profiles. Ongoing PK/PD analyses aim to guide the trial’s dose-expansion phase and further clinical development.
References:
- TransCode Therapeutics announces initial dosing in fourth cohort of phase 1 clinical trial with TTX-MC138. News release. TransCode Therapeutics, Inc. March 27, 2025. Accessed March 31, 2025. https://tinyurl.com/bdhwd4jh
- TransCode Therapeutics announces safety review committee approval to open fourth cohort in phase I/II clinical trial. News release. TransCode Therapeutics, Inc. March 13, 2025. Accessed March 31, 2025. https://tinyurl.com/2zrxdxad
- Study of TTX-MC138 in subjects with advanced solid tumors. ClinicalTrials.gov. Updated January 27, 2025. Accessed March 31, 2025. https://tinyurl.com/4mrbdn7u
