Telix Pharmaceuticals Limited (ASX: TLX, NASDAQ: TLX) has dosed the first patient with TLX250-Tx (lutetium-177 (177Lu) girentuximab tetraxetan) in its Phase 3 LUTEON study for relapsed or recurrent clear cell renal cell carcinoma (ccRCC). This marks the first radiopharmaceutical therapy to enter Phase 3 development for ccRCC, a significant milestone in targeted treatments for this aggressive cancer subtype. The study aims to address the poor outcomes for patients with relapsed or recurrent ccRCC, despite advances in care.

The patient was dosed at GenesisCare Murdoch in Western Australia under the supervision of Dr. Aviral Singh, Clinical Head of Theranostics and Nuclear Medicine at GenesisCare Murdoch and Principal Investigator on the LUTEON trial. Dr. David N. Cade, Telix Group Chief Medical Officer, highlighted that LUTEON represents the next stage in Telix’s global clinical development of TLX250-Tx.

TLX250-Tx is a first-in-class CAIX-targeting radio antibody-drug conjugate (rADC) therapy candidate composed of a high-specificity monoclonal antibody chelated to the therapeutic radionuclide lutetium-177. CAIX is expressed in more than 95% of ccRCC cases, with limited expression in normal tissues, making it an attractive therapeutic target.

The LUTEON study is a randomized, prospective, open-label, multi-center trial being conducted under a Phase 3 protocol in Australia. It forms part of Telix’s global development program for TLX250-Tx, which includes the separate Phase 2a LUTEON ATLAS study in the United States and Europe. The study utilizes Telix’s investigational PET imaging agent, TLX250-Px (Zircaix), to identify eligible patients with CAIX-positive tumors.

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer, representing about 85% of all renal cell carcinoma (RCC) cases. Up to 30% of patients present with metastatic disease at diagnosis, which has a 20% five-year survival rate. Telix’s commercial franchise is anchored by its prostate cancer imaging portfolio, Illuccix and Gozellix, while its late-stage therapeutic pipeline includes three assets in pivotal-stage trials, including TLX250-Tx for kidney cancer.

Telix Pharmaceuticals Limited and St Vincent’s Hospital have dosed the first patients with TLX597-Tx in the OPTIMAL-e trial for metastatic hormone-sensitive prostate cancer (mHSPC). The Phase 2 study, led by Professor Louise Emmett at St Vincent’s Hospital in Sydney, Australia, evaluates an adaptive-dosed radioligand therapy aimed at improving efficacy and quality of life in earlier-stage disease. The trial builds upon the OPTIMAL-PSMA study, which recently completed patient enrollment.

OPTIMAL-e is a single-arm, open-label trial assessing TLX597-Tx in combination with androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI). The study focuses on the therapy's impact on prostate-specific antigen (PSA) response rates, evaluating its potential to deepen and sustain responses while monitoring the safety of dose intensification. The adaptive approach involves continuing treatment when the PSMA target persists and pausing it upon significant tumor burden reduction, guided by PSMA-PET imaging and PSA measurements.

TLX597-Tx is a next-generation small molecule radioligand therapy targeting PSMA. It has demonstrated favorable biodistribution and dosimetry in prior studies, including OPTIMAL-PSMA, with low exposure to salivary glands and kidneys and high uptake in PSMA-expressing tumors. The therapy is designed to address earlier-stage metastatic prostate cancer, where maintaining quality of life is a critical treatment goal.

Louise Emmett, MD, Director of Theranostics and Nuclear Medicine at St Vincent’s Hospital and Lead Investigator, emphasized the trial's individualized strategy. "By using PSMA-PET imaging and PSA measurements to monitor disease burden, treatment can be continued when the PSMA target persists, and paused when there is a significant reduction in tumor burden," Emmett said. "This approach aims to maintain disease control while minimizing unnecessary treatment exposure."

David N. Cade, MD, Group Chief Medical Officer at Telix, highlighted the significance of earlier intervention. "While the currently approved radioligand therapy has demonstrated a modest improvement in overall survival in advanced-stage disease, we believe earlier intervention may offer the potential to further improve outcomes and prolong quality of life for patients," Cade stated.

TLX597-Tx is part of Telix’s broader prostate cancer portfolio, which includes TLX591-Tx, currently in Phase 3 trials for metastatic castration-resistant prostate cancer (mCRPC). The two therapies exhibit complementary modes of action, targeting different stages of the disease. TLX597-Tx has not received marketing authorization in any jurisdiction.