TransCode Therapeutics Advances TTX-MC138 to Phase 2a Trial for Minimal Residual Disease in Colorectal Cancer
核心洞察
TransCode Therapeutics and Quantum Leap Healthcare Collaborative (搜索) announced a Phase 2a dose-expansion trial for TTX-MC138, enrolling up to 45 colorectal cancer (搜索) patients with minimal residual disease (搜索).
The first-in-class therapeutic candidate targets microRNA-10b (搜索) and demonstrated safety and durable clinical benefit in Phase 1a trials, establishing a recommended Phase 2 dose.
The trial will evaluate TTX-MC138 in patients who completed standard therapy but remain ctDNA positive, addressing a critical unmet need in preventing cancer recurrence.
TransCode Therapeutics has partnered with Quantum Leap Healthcare Collaborative (搜索) to advance its lead therapeutic candidate TTX-MC138 into a Phase 2a dose-expansion clinical trial targeting minimal residual disease (搜索) in colorectal cancer (搜索) patients. The collaboration leverages the PRE-I-SPY clinical trial platform to evaluate the first-in-class microRNA inhibitor in a critical treatment setting where few effective options exist.
Phase 2a Trial Design and Patient Population
The Phase 2a portion of the trial will enroll up to 45 patients with colorectal cancer (搜索) who have completed standard curative-intent therapy but remain circulating tumor DNA (ctDNA) positive. Dr. Paula Pohlmann of MD Anderson Cancer Center will serve as the Principal Investigator, with trial initiation planned for the first half of 2026.
The study targets patients in the Minimal Residual Disease (搜索) (MRD) setting, where therapeutic intervention may have the greatest opportunity to improve long-term outcomes. The decision to focus on patients who have demonstrated a pathological complete response following standard-of-care therapy but have evidence of circulating tumor DNA is based on the high degree of recurrence in those patients and the lack of effective therapies in that setting.
Mechanism of Action and Clinical Rationale
TTX-MC138 is designed to inhibit microRNA-10b (搜索) (miR-10b (搜索)), a microRNA widely believed to be critical to the emergence and progression of many metastatic cancers. The drug offers a therapeutic option in the MRD setting because of its mechanism of action specifically targeting metastatic disease combined with an excellent safety profile.
"The safety and durable clinical benefit observed in TransCode's Phase 1a trial with TTX-MC138 provide the basis for TransCode's decision to proceed with Phase 2a clinical testing," noted Daniel Vlock, MD, TransCode's Consulting Clinician. "The observed safety profile, coupled with the durability of TTX-MC138's anti-tumor effects, is particularly encouraging. These findings are consistent with the drug's mechanism of action and provide a basis for a more rigorous efficacy evaluation."
Phase 1a Trial Results
TransCode's Phase 1a first-in-human clinical trial achieved its primary safety endpoint and established a recommended Phase 2 dose, as announced at ESMO 2025. The trial demonstrated safety and durable clinical benefit, positioning the company to potentially intervene earlier in the patient's disease and offering a new therapeutic option for patients at risk of developing metastatic disease.
Addressing Unmet Medical Need
"Detecting and treating micrometastatic disease before it becomes visible is one of the biggest unmet challenges in cancer," said Laura Esserman, M.D., co-founder of Quantum Leap, and Professor of Surgery and Radiology at the University of California, San Francisco. "The PRE-ISPY Trial is uniquely positioned to rapidly evaluate agents like TTX-MC138 that may eradicate minimal residual disease (搜索) and prevent recurrence in colorectal and eventually other cancer."
PRE-I-SPY Platform Advantages
The PRE-I-SPY platform extends I-SPY into early feasibility testing to accelerate biologically targeted therapies into the I-SPY 2.2 high-risk curative setting. The I-SPY Trials were designed to rapidly screen promising experimental treatments and identify those most effective for biologically defined patient subgroups, representing a unique collaboration among the U.S. Food and Drug Administration, industry partners, patient advocates, philanthropic sponsors, and clinicians across leading U.S. cancer research centers.
Quantum Leap Healthcare Collaborative (搜索), a 501(c)(3) nonprofit organization founded in 2005 by UCSF researchers and Silicon Valley innovators, sponsors and manages the I-SPY Trial programs. The organization's mission is to integrate clinical care with research, advance high-impact platform trials, and improve patient outcomes through adaptive learning systems, enhanced data infrastructure, and widespread trial accessibility.
Company Profile and Pipeline
TransCode Therapeutics is a clinical stage company pioneering immunoncology and RNA therapeutic treatments of high risk and advanced cancers. The company's lead therapeutic candidate, TTX-MC138, is focused on treating metastatic tumors that overexpress microRNA-10b (搜索), a unique, well-documented biomarker of metastasis. In addition, TransCode has a portfolio of other first-in-class therapeutic candidates designed to mobilize the immune system to recognize and destroy cancer cells.