TLX250-CDx Indication Expansion: Preliminary Data Presented at EANM

Melbourne (Australia) | 17 October 2022

  • OPALESCENCE Phase II feasibility study of TLX250-CDx in patients with triple-negative breast cancer – early results suggest potential to detect carbonic anhydrase IX (CAIX) expression, theranostic potential in this difficult to treat disease.
  • PERTINENCE Early Phase I feasibility study of TLX250-CDx in patients with non-muscle-invasive bladder cancer, a collaboration with ATONCO – early results support translation to first-in-human therapeutic studies with the alpha-emitting radioisotope astatine-211 (211At).
  • Both investigator-initiated studies being undertaken by Dr. Caroline Rousseau at the Institut de Cancérologie de l’Ouest (ICO) in St Herblain (France).
  • Results delivered at the European Association of Nuclear Medicine (EANM) Annual Congress currently taking place in Barcelona, Spain.

Telix today announces preliminary data from two separate investigator-initiated studies of TLX250-CDx (89Zr-DFO-girentuximab) in triple negative breast cancer (TNBC) and non-muscle-invasive bladder cancer (NMIBC), part of a comprehensive series of studies evaluating CAIX expression in cancers other than clear cell renal cell carcinoma (ccRCC), supporting Telix’s goal to rapidly expand the CAIX program into other indications beyond kidney cancer.

OPALESCENCE Phase II study of TLX250-CDx in triple-negative breast cancer reports preliminary data as a top-rated oral presentation at EANM

The primary objective of OPALESCENCE (NCT04758780) is to evaluate how carbonic anhydrase IX (CAIX) targeting imaging with positron emission tomography (PET) can be utilised for the diagnosis and staging of triple-negative breast cancer (TNBC) and to develop a deeper understanding of CAIX as a potential therapeutic target in this patient population with a significant unmet medical need.

Preliminary data demonstrates the feasibility of girentuximab to target CAIX expression in TNBC. Early results suggest potential for girentuximab as an imaging agent and therapeutic in this poor prognosis disease: 83% patient lesions had a CAIX strong expression allowing TLX250-CDx immunoPET detection, showing promise for further investigation. Three patients have all of their lesions detected by TLX250-CDx immunoPET. The best detected metastatic sites are bone.

Based on these results, TLX250-CDx is an attractive novel investigative targeting agent for TNBC and potential alternative to biopsy and immunohistochemistry (IHC) for staging metastatic disease and targeted radioligand therapy.

Should the targeting properties of this PET/CT imaging tracer be established in TNBC, Telix’s intention is to broaden future applications for lutetium-177 and actinium-225 based CAIX therapies.

Principal Investigator for the OPALESCENCE study, Dr. Caroline Rousseau stated, “We are pleased to announce preliminary results of this prospective pilot study of Telix’s investigational CAIX targeting imaging agent in TNBC. Early indications are that TLX250-CDx is showing promise as a diagnostic targeting agent in this disease, and we look forward to completing the study and presenting full results.”

Telix Chief Medical Officer, Dr. Colin Hayward stated, “Identifying new targets and treatment strategies for TNBC is a major unmet need, given the aggressive behaviour and distinct patterns of metastasis that characterise this cancer, and the lack of targeted therapies. Whilst a small patient population at this stage, early data from the OPALESCENCE study is encouraging as an indicator for future therapy applications of TLX250 and demonstrating the value of a “theranostic” approach” with this radiolabelled antibody. We would like to thank Dr. Caroline Rousseau and her clinical team at ICO for their commitment to this important study, and the patients who have contributed to date.”

PERTINENCE pilot open-label, feasibility study of alpha therapy target reports preliminary data

The objective of PERTINENCE (NCT04897763), an open-label, proof of concept study, is to evaluate safety profile, biodistribution and tumour targeting properties of TLX250-CDx given directly into the bladder in patients with NMIBC and to establish carbonic anhydrase IX (CAIX) as a potential therapeutic target in this condition.

Preliminary data from this feasibility, dosimetry and imaging study at ICO1, shows encouraging tumour targeting and biodistribution with TLX250-CDx, and no systemic distribution of radiation.

Based on these results, Telix’s partner ATONCO intends to progress TLX250 labelled with the alpha-emitter astatine-211 (211At) into a first-in-human Phase I targeted alpha therapy (TAT) study.

Patients with NMIBC currently have few therapeutic options with the risk of complete cystectomy (bladder removal). Therefore, new treatment options with preservation of the urinary bladder are urgently needed to address unmet medical need. Carbonic anhydrase (CAIX) is a cell surface protein that is highly expressed in many hypoxic solid tumours and a potential therapeutic target in NMIBC using a novel approach with TAT instilled directly into the bladder. This is aligned with Telix’s strategy to develop diagnostics and radioconjugates as therapeutics with both alpha and beta emitters in new indications beyond kidney cancer.

Alpha emitters such as 211At have the potential to deliver very high amounts of energy to cancer tissue whilst the short path length can decrease the risk of damage to surrounding healthy cells, increasing both the selectivity and potency of the radiation treatment. The prospective indications for alpha emitters are complementary to beta emitters due to their different properties: alpha therapies have a shorter penetration depth into tumours to suit smaller or disseminated tumours or micro-metastatic disease.

Preliminary Results
Four of six patients refractory to prior BCG therapy are included in current analysis:
• TLX250-CDx PET/CT showed intravesical radioactivity confined to the bladder and good tumour targeting.
• TLX250-CDx positivity was concordant to positive and negative immunohistochemistry results for CAIX expression.
• TLX250-CDx was well tolerated with an encouraging safety profile, suggesting feasibility for future alpha-immunotherapy development in patients with NMIBC.

Principal investigator for the PERTINENCE study, sponsored by ICO, Dr. Caroline Rousseau said, “We are pleased to present preliminary data from this proof-of-concept study of TLX250-CDx in NMIBC. Early results for safety profile, biodistribution and dosimetry are encouraging and support translation to therapeutic studies with the alpha-emitting radioisotope astatine-211 (211At).”

Telix Chief Medical Officer, Dr Colin Hayward and ATONCO Chief Medical Officer, Dr Jean-François Chatal together added, “These results are an important step towards using TLX250 with an alpha emitting isotope for the first time in humans.” Dr Colin Hayward continued, “Telix is looking forward to continuing to support ATONCO in its development of 211At-labelled TLX250 for patients with NMIBC and establishing CAIX as a therapeutic target beyond kidney cancer in a series of important scientific studies.”

[1] Telix press release 24 August 2022

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