Telix reports long-term data for investigational TLX400-Tx in advanced medullary thyroid carcinoma, showing 80% disease control, 26-month PFS, and acceptable safety.
Written by: Mayuresh Salvi, PharmD
Reviewed by: Pharmacally Editorial Team
Telix Pharmaceuticals has announced the publication of long-term clinical outcomes from an investigator-led study evaluating TLX400-Tx (¹⁷⁷Lu-DOTAGA.Glu.(FAPi)₂), its lead fibroblast activation protein (FAP)-targeted radiopharmaceutical therapy, in patients with advanced or metastatic medullary thyroid carcinoma (MTC).
According to the company, the findings, published in EJNMMI Research, demonstrated encouraging preliminary efficacy signals, including an 80% disease control rate, a median progression-free survival (PFS) of 26 months, a median overall survival (OS) of 42 months, and an acceptable safety profile in a heavily pretreated patient population.
The findings add to growing evidence supporting FAP-targeted radioligand therapy as a potential treatment strategy for solid tumors with limited therapeutic options.
Limited Treatment Options in Advanced MTC
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy accounting for approximately 1% to 5% of all thyroid cancers. While surgery remains the standard treatment for localized disease, patients with metastatic or unresectable MTC have limited therapeutic options. Current systemic therapies, including the tyrosine kinase inhibitors (TKIs) vandetanib and cabozantinib, as well as selective RET inhibitors such as selpercatinib, can delay disease progression. However, durable responses remain uncommon, resistance may develop, and treatment-related toxicities can adversely affect long-term quality of life.
Study Design
The investigator-led retrospective real-world analysis included 17 evaluable patients with progressive, locally advanced, or metastatic MTC treated under a compassionate-use program. Most participants had previously received systemic therapy and had exhausted standard treatment options.
Patients received a median of five treatment cycles of TLX400-Tx, while a subset underwent tandem ¹⁷⁷Lu/²²⁵Ac-DOTAGA.Glu.FAPi dimer therapy. Treatment efficacy was assessed using RECIST 1.1 (Response Evaluation Criteria in Solid Tumors), together with progression-free survival, overall survival, and safety outcomes.
Encouraging Efficacy and Safety
According to Telix, TLX400-Tx achieved an 80% disease control rate, including a 33% partial response rate and 47% stable disease. Patients experienced a median PFS of 26 months and a median OS of 42 months, suggesting durable disease control in a population with advanced disease and limited remaining treatment options.
The therapy also demonstrated an acceptable safety profile. No dose-limiting toxicities were reported, while the overall hematologic and hepatic safety profile was considered acceptable in this advanced patient population. The investigators concluded that the findings support the tolerability of TLX400-Tx during the study period.
Why FAP-Targeted Therapy Matters
Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts within the tumor microenvironment of many solid tumors. Unlike therapies directed solely at malignant cells, FAP-targeted radiopharmaceuticals are designed to disrupt the tumor microenvironment by delivering targeted radiation to both stromal tissue and adjacent tumor cells.
TLX400-Tx has been engineered to improve tumor retention while minimizing off-target radiation exposure compared with earlier-generation FAP-targeting agents, supporting its continued investigation across multiple solid tumor types.
Expert Perspective
Lead investigator Dr. Sanjana Ballal, Senior Researcher at the All India Institute of Medical Sciences (AIIMS), New Delhi, said the findings highlight the potential of TLX400-Tx for patients with advanced MTC who have exhausted standard therapies or have limited treatment options remaining, while emphasizing that the encouraging safety and preliminary efficacy signals warrant validation in larger prospective clinical studies.
Dr. David N. Cade, Group Chief Medical Officer at Telix Pharmaceuticals, stated that the findings further reinforce the scientific potential and versatility of the company’s FAP-targeting platform and support the continued clinical development of TLX400-Tx across multiple solid tumors.
Clinical Perspective
Although derived from a small retrospective compassionate-use cohort without a randomized comparator arm, the reported efficacy and safety outcomes are encouraging in a disease with limited therapeutic options after progression on currently available targeted therapies. These findings should be considered hypothesis-generating and require confirmation in larger prospective clinical studies before the role of TLX400-Tx in advanced medullary thyroid carcinoma can be fully established.
TLX400-Tx has not received marketing authorization in any jurisdiction and remains an investigational FAP-targeted radiopharmaceutical therapy.
Reference
About the Writer
Mayuresh Sunil Salvi (Linkedin) is a PharmD professional and healthcare writer with a strong interest in pharmacovigilance, drug safety, and emerging medical research. He is passionate about exploring new drug discoveries, clinical research, and advances in evidence-based medicine. His interests also include ward rounds, prescription audits, and treatment analysis to support rational pharmacotherapy and improved patient care.