TLX250-CDx Shows Promise in Triple Negative Breast Cancer as OPALESCENCE Trial Results Published
Key Insights
The Phase 2 OPALESCENCE trial demonstrated TLX250-CDx PET/CT imaging achieved 87.5% overall sensitivity in detecting metastatic triple negative breast cancer (search) lesions.
TLX250-CDx successfully detected all brain metastases confirmed by MRI, while FDG PET/CT detected only one-third of brain lesions.
The study confirms carbonic anhydrase IX (search) expression in TNBC and supports potential theranostic applications for this aggressive cancer subtype.
Telix Pharmaceuticals has published final positive results from the Phase 2 OPALESCENCE trial of TLX250-CDx (89Zr-girentuximab) in metastatic triple negative breast cancer (search) (mTNBC) in the European Journal of Nuclear Medicine and Molecular Imaging. The prospective, single-center investigator-initiated trial conducted at the Institut de Cancérologie de l'Ouest (search) in France evaluated the safety, sensitivity, and diagnostic utility of TLX250-CDx PET/CT imaging in women with mTNBC.
Strong Sensitivity Across Multiple Metastatic Sites
The pilot study of twelve patients demonstrated impressive diagnostic performance with an overall sensitivity of 87.5%. The imaging agent showed 100% sensitivity for detecting lesions in breast, skin, and adrenal gland locations. Expression in lymph nodes and bone lesions reached 88.0% and 91.9%, respectively.
A particularly notable finding was TLX250-CDx PET/CT's superior performance in brain metastasis detection. The imaging method detected all brain metastases that were confirmed by MRI, whereas conventional FDG PET/CT detected only one-third of brain lesions. Despite this enhanced sensitivity for brain lesions, tumor burden analysis using total tumor volume was equivalent between both PET/CT methods.
Safety Profile and Mechanism of Action
The trial reported no safety issues following TLX250-CDx administration. The imaging agent works by targeting carbonic anhydrase IX (search) (CAIX (search)), a protein that the study confirmed is expressed in TNBC. This mechanism allows for effective tumor targeting and high-quality imaging.
Principal Investigator Dr. Caroline Rousseau noted that TLX250-CDx has already demonstrated high sensitivity and specificity in clinical trials for clear cell renal cell carcinoma (search) detection. "Now it has also exhibited potential utility in metastatic triple negative breast cancer (search), an aggressive form of breast cancer (search)," she stated. "These results demonstrate the ability of TLX250-CDx to identify lesions that may be resistant to treatment due to their aggressive profile resulting from hypoxia, in patients with limited options for therapeutic management."
Expanding Theranostic Applications
The study authors conclude that TLX250-CDx immuno-PET "is a sensitive imaging method and offers promise for novel theranostics for mTNBC patients." This finding builds on preliminary results previously presented at the European Association of Nuclear Medicine Annual Congress in 2022 and the San Antonio Breast Cancer (search) Symposium in 2023.
Dr. David N. Cade, Group Chief Medical Officer at Telix, emphasized the significance for future therapeutic development: "We are encouraged by this data in triple negative breast cancer (search), which remains an area of significant unmet need. Proof of concept for CAIX (search)-targeted imaging supports the expansion of this potential pan-tumor program into new indications beyond renal cancer, including future applications for lutetium-177 (177Lu) and actinium-225 (search) (225Ac) based therapies."
Clinical Context and Unmet Need
Triple negative breast cancer (search) represents a particularly challenging subset of breast cancer, accounting for approximately 10-15% of all breast cancers. The disease is characterized by the absence of estrogen and progesterone receptors and HER2 protein, which limits treatment options. TNBCs differ from other invasive breast cancers in that they grow and spread faster, have limited treatment options, and carry a poorer prognosis.
Breast cancer (search) remains the most common cancer in women and the second most common cancer overall. In 2022, almost 2.3 million women were diagnosed with breast cancer globally, with 666,000 deaths from the disease.
TLX250-CDx has not received marketing authorization in any jurisdiction. The compound was supplied by Telix and authorized for use by ICO during the clinical study, representing an important step in expanding the potential applications of CAIX (search)-targeted imaging beyond renal cancer into other tumor types with significant unmet medical needs.