New Cohort Approved in Phase 1/2 Trial of TTX-MC138 in Solid Cancers

Based on positive safety data from the third cohort, a safety review committee approved the opening of a fourth cohort as well as more enrollment into the third cohort.

A fourth cohort will be opening in the phase 1/2 trial (NCT06260774) evaluating the safety and tolerability of TTX-MC138, a first-in-class therapeutic candidate targeting microRNA-10b, as a treatment in patients with advanced solid tumors, according to a press release from the developer, TransCode Therapeutics.¹

The safety review committee that was monitoring the trial unanimously approved the addition of the extra cohort after a favorable review of the third cohort’s safety data. The committee also approved the enrollment of more patients into cohort 3. Patients are currently being evaluated for eligibility in cohort 4.

Pharmacokinetic and pharmacodynamic data from patients in cohort 1 and cohort 2 were consistent with what was observed in the phase 0 trial (NCT05908773). Of the 9 patients enrolled in the first 3 cohorts, 6 remain on treatment due to the absence of dose limiting toxicities and disease progression. No significant safety or dose limiting toxicities were reported in cohorts 1, 2, and 3.

Early results from a pharmacokinetic analysis demonstrated that the dose levels from cohorts 1 and 2, 0.8 mg/kg to 1.6 mg/kg, represent an efficacious range.

“The [safety review committee] approval to open the fourth cohort and expand enrollment in cohort 3 is an important advancement for the clinical trial. It will provide an opportunity to obtain additional safety and [pharmacokinetic/pharmacodynamic] data, inform the dose expansion stage of the clinical trial and may allow us to obtain initial evidence of clinical activity,” Sue Duggan, senior vice president of Operations at TransCode stated in the press release.¹ “Enrollment into the study continues based on the cumulative safety data review. Eligible subjects may now be screened and scheduled in cohort 4 for treatment with the next dose level of TTX-MC138 while preliminary data analysis continues.”

The multicenter, open-label, dose-escalation and expansion trial has currently treated 9 patients who have a variety of metastatic solid cancers with TTX-MC138; there was an initial dose-escalation stage followed by a dose-expansion stage. Dosage was increased incrementally in cohorts subsequent to the first to find the maximum tolerated dose.

Patients in cohort 1 received 0.4 mg/kg of TTX-MC138, patients in cohort 2 received 0.8 mg/kg, and patients in cohort 3 received 3.2 mg/kg.² Treatment cycles were 28 days long and patients received 1 dose of TTC-MC138 via intravenous infusion on day 1 of every cycle.

Eligible patients were 18 years or older and had a histologically or cytologically confirmed diagnosis of relapsed or refractory metastatic or locally advanced solid tumor where no standard therapy exists, standard therapy has failed, and standard therapies have no known clinical benefit. Additionally, patients had measurable or evaluable disease per RECIST v1.1, an ECOG performance status from 0 to 2, a life expectancy of 3 months or greater, and adequate organ function.

Those who had history of a second malignancy that required active therapy in the past year, received anticancer therapy within 14 days or 5 half-lives of study drug administration, had central nervous system metastases, required treatment with traditional/herbal medicines, had any severe or uncontrolled systemic disease or condition, had a history of acute ischemic stroke, had a clinical diagnosis of hemochromatosis or secondary iron overload, and have any unresolved clinically relevant toxicities from prior therapies were excluded from participating in the trial.

The trial’s end points in the dose escalation phase were adverse effects defined as the safety and tolerability of escalating dose levels to determine the incidence of treatment-emergent adverse events and overall response rate defined as the proportion of patients to achieve complete response, partial response, or stable disease for at least 8 weeks per RECIST v1.1.

In the abstract of a presentation given on the phase 0 trial of TTX-MC138 at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, lead study author Zdravka Medarova, PhD, an associate professor of Radiology at Harvard Medical School, and coauthors, wrote that the therapy “represents a first step towards developing effective nucleic-acid based therapeutics against cancer.”³

References

1. 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 13, 2025. https://tinyurl.com/2zrxdxad
2. Study of TTX-MC138 in subjects with advanced solid tumors. ClinicalTrials.gov. Updated January 27, 2025. Accessed March 13, 2025. https://tinyurl.com/4mrbdn7u
3. Medarova Z, Robertson N, Ghosh S, et al. Initial clinical experience with the first-in-class anti-metastasis therapeutic TTXMC138. J Clin Oncol. 2024;42(supp_16):e15072. doi:10.1200/JCO.2024.42.16_suppl.e15072