TransCode Therapeutics Advances TTX-MC138 to Phase 2a Trial Following Successful Phase 1a Results in Metastatic Cancer
Key Insights
TransCode Therapeutics has initiated a Phase 2a clinical trial for TTX-MC138 in ctDNA-positive colorectal cancer (search) patients following successful completion of Phase 1a studies.
The Phase 1a trial demonstrated strong safety profile with no dose-limiting toxicities and achieved 64% stable disease rate in evaluable metastatic cancer (search) patients.
TTX-MC138 represents a first-in-class therapeutic targeting microRNA-10b (search), with three patients continuing treatment for over 14 cycles showing durable disease control.
TransCode Therapeutics has successfully completed its Phase 1a clinical trial of TTX-MC138 and initiated a Phase 2a study targeting minimal residual disease in colorectal cancer (search) patients, marking a significant milestone for the first-in-class microRNA inhibitor.
Phase 1a Trial Demonstrates Safety and Efficacy Signals
The completed Phase 1a trial enrolled 16 patients with metastatic cancer (search) who received a total of 86 doses of TTX-MC138. The study achieved its primary safety endpoint with no dose-limiting toxicities observed, establishing a recommended Phase 2 dose of 4.8mg/kg. The median treatment duration was 11.3 weeks, ranging from four to 52.4 weeks, representing 2 to 20 cycles of treatment.
"From a clinical perspective, it is quite encouraging to see how well tolerated this agent has been at the exposures achieved through the Phase 1a dose-escalation study, without any dose-limiting toxicities," noted Keith Flaherty, MD, Director of Clinical Research at the Massachusetts General Hospital Cancer Center and TransCode Advisory Board member.
Notably, three patients remain on trial and continue receiving TTX-MC138, with one patient completing 21 cycles of treatment, another at 16 cycles, and a third at 14 cycles. Based on RECIST criteria, 9 out of 14 evaluable patients (64%) achieved stable disease lasting six months, demonstrating durable disease activity in this advanced cancer population.
Promising Biomarker Response in Thyroid Cancer Patient
One patient with metastatic thyroid cancer (search) showed a dramatic decrease in thyroglobulin levels, a tumor marker associated with cancer progression. This patient has maintained stable disease for 12 months and remains on study, providing evidence of therapeutic activity from TTX-MC138.
The pharmacokinetics analysis from patient plasma samples demonstrated drug bioavailability consistent with earlier preclinical studies, supporting the compound's clinical development trajectory.
Phase 2a Trial Targets Minimal Residual Disease
The newly initiated Phase 2a trial will evaluate TTX-MC138 in patients with circulating tumor DNA (ctDNA) positive colorectal cancer (search) following curative-intent therapy. The study expects to enroll up to 45 patients who have completed standard treatment with no radiographic evidence of disease but remain ctDNA-positive, indicating minimal residual disease presence.
The trial is being conducted through the PRE-I-SPY platform in collaboration with Quantum Leap Healthcare Collaborative (search), with principal investigators Dr. Emil Lou of the University of Minnesota and Dr. Zhaohui Jin of the Mayo Clinic Comprehensive Cancer Center. Dr. Paula Pohlmann of MD Anderson Cancer Center chairs the trial.
Novel Mechanism Targeting Metastatic Progression
TTX-MC138 represents a first-in-class therapeutic designed to inhibit microRNA-10b (search) (miR-10b (search)), a microRNA widely believed critical to the emergence and progression of metastatic cancers. The compound targets metastatic tumors that overexpress miR-10b, a well-documented biomarker of metastasis.
"TTX-MC138's safety profile, coupled with the durability of its anti-tumor effects, observed in TransCode's Phase 1a clinical trial is particularly encouraging," stated Daniel Vlock, MD, TransCode's Consulting Clinician. "This positions TransCode and its collaborators to potentially intervene earlier in a patient's disease, and may in the future offer a new therapeutic option for patients at risk of developing metastatic disease."
Strategic Platform Collaboration
The Phase 2a trial leverages clinical sites participating in QLHC's PRE-I-SPY platform trial, including several National Comprehensive Cancer Network (NCCN) centers with considerable expertise in defining standard-of-care cancer treatment practices. The trial has received FDA submission and Institutional Review Board approval, enabling site activation and patient enrollment commencement.
The study aims to generate new data about ctDNA testing importance and TTX-MC138's role in reducing cancer recurrence risk in this at-risk patient population, building on growing clinical momentum supporting ctDNA-guided strategies for minimal residual disease targeting in colorectal cancer (search).