177Lu-DOTA-girentuximab (TLX250) / Telix, China Grand Pharma - LARVOL DELTA

Prospective pilot study with [89Zr]Zr-girentuximab PET/CT: CA-IX imaging in metastatic triple negative breast cancer (OPALESCENCE). (PubMed, Eur J Nucl Med Mol Imaging) - P2 | "[89Zr]Zr-girentuximab PET/CT is a sensitive imaging method and offers promise for novel theranostics for mTNBC patients."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CA9

Development of a multi-functional CAIX-TGFβ targeted radiopharmaceutical for triple-negative breast cancer (AACR-NCI-EORTC 2025) - "Radiation-induced blood cell cytotoxicity at the early stage may require treatment optimization or additional cell survival factors to alleviate the early cytotoxicity. Overall, Lu-177 labeled TLX250-TRAP enables theranostic use to track tumors and promotes therapeutic antitumor immune responses in TNBC."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CA9 • CD4 • CD8 • TGFB1

TLX250-CDx (Zircaix) Included in Leading International Guidelines for Renal Imaging (Telix Press Release) - "The panel asserts that antibody-based radiotracers exhibit lower renal clearance, thereby improving visualization of renal masses. It emphasizes that TLX250-CDx PET 'appears to be a well-tolerated and accurate method for non-invasive identification of ccRCC6' and notes by contrast, the high renal excretion with 18F-FDG PET, which obscures accurate lesion detection...The panel references data from Telix’s pivotal Phase 3 ZIRCON trial..."

Clinical guideline • Clear Cell Renal Cell Carcinoma

Carbonic Anhydrase IX-Targeting for Radioimmunotherapy in Triple-Negative Breast Cancer (EANM 2025) - "The objective of this study was to evaluate Girentuximab theranostic potential as (i) a diagnostic tool (TLX250-CDx - Zirconium-89-labelled Girentuximab) to identify tumour-specific targeting in TNBC, and (ii) a radioimmunotherapeutic tool (TLX250 - Lutetium-177-labelled Girentuximab) to treat TNBC when given as a single agent or in combination with conventional chemotherapy - Capecitabine. The presented results give first evidence of its ability to effectively target and control tumour growth in a TNBC xenograft model, particularly when combined with chemotherapy. Additional studies are now being conducted to further expand on the therapeutic application of Girentuximab-based RIT in TNBC."

IO biomarker • Breast Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer • CA9

Effects of Belzutifan on 89Zr-DFO-girentuximab PET Uptake in Patients With Renal Cell Carcinoma (RCC) (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: NYU Langone Health | Not yet recruiting ➔ Recruiting

Enrollment open • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Effects of Belzutifan on 89Zr-DFO-girentuximab PET Uptake in Patients With Renal Cell Carcinoma (RCC) (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: NYU Langone Health

New P1 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

LUTEON: Study of 177Lu-TLX250 in Advanced Relapsed or Recurrent ccRCC (clinicaltrials.gov) - P3 | N=40 | Not yet recruiting | Sponsor: Telix Pharmaceuticals (Innovations) Pty Limited

New P3 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

STARLITE-1: 177Lu-girentuximab, cabozantinib & nivolumab in ccRCC (YouTube) - "Eric Jonasch, MD... describes the Phase Ib/II STARLITE-1 trial (NCT05533242) of 177Lu-girentuximab with cabozantinib and nivolumab in treatment-naïve patients with advanced clear cell renal cell carcinoma (ccRCC)."

Video

Preclinical evaluation of Zr-89/Lu-177-girentuximab as a CA-IX targeting theranostic agent in metastatic colorectal cancer (SNMMI 2025) - "PET imaging of 89Zr-girentuximab demonstrated high tumour uptake (SUVmax=5.6±0.9) and tumour-to-background ratio (TBR=11.0±1.9) at 168h post-injection (Fig 1a.). Corresponding 18F-FDG tumour uptake was low (SUVmax=0.6±0.1). Mice treated with 177Lu-girentuximab showed inhibited tumour growth from day 8 to 22 post treatment (Fig 1b.), a slower regrowth rate, and a significant median survival increase from 42 days to 68 days (P=0.02), compared with mice that received unlabelled girentuximab (Fig 1c.)."

Metastases • Preclinical • Colorectal Cancer • Oncology • Solid Tumor • CA9

Preclinical evaluation of Zr-89/Lu-177-girentuximab as a CA-IX targeting theranostic agent in metastatic colorectal cancer (SNMMI 2025) - "PET imaging of 89Zr-girentuximab demonstrated high tumour uptake (SUVmax=5.6±0.9) and tumour-to-background ratio (TBR=11.0±1.9) at 168h post-injection (Fig 1a.). Corresponding 18F-FDG tumour uptake was low (SUVmax=0.6±0.1). Mice treated with 177Lu-girentuximab showed inhibited tumour growth from day 8 to 22 post treatment (Fig 1b.), a slower regrowth rate, and a significant median survival increase from 42 days to 68 days (P=0.02), compared with mice that received unlabelled girentuximab (Fig 1c.)."

Metastases • Preclinical • Colorectal Cancer • Oncology • Solid Tumor • CA9

ASCO 2025: STARLITE 2: Phase 2 Study of Nivolumab plus 177lutetium-Labeled Anti–carbonic Anhydrase IX (CAIX) Monoclonal Antibody Girentuximab (177Lu-Girentuximab) in Patients with Advanced Clear Cell Renal Cell Carcinoma (ccRCC) (UroToday) - "The STARLITE 2 trial is a phase 2, open-label, single-arm study evaluating the combination of lutetium-177 (¹⁷⁷Lu)-girentuximab and nivolumab in patients with previously treated ccRCC. The study includes a safety lead-in phase to determine the maximum tolerated dose (MTD) of ¹⁷⁷Lu-girentuximab in combination with nivolumab, starting at 75% of the single-agent ¹⁷⁷Lu dose. Once the MTD is established, a Simon two-stage design will be implemented to assess the efficacy of this combination. Patients treated at the MTD during the safety lead-in will be included in the first stage of the phase 2 portion. Notably, the prespecified number of dose-limiting toxicities (DLTs) was exceeded in cohort 2, leading to a dose adjustment back to 1804 MBq/m²."

Clinical protocol • Clear Cell Renal Cell Carcinoma

Telix at ANZSNM Annual Scientific Meeting 2025 (PRNewswire) - "Telix Pharmaceuticals Limited...announces a strong presence at the 55th Annual Scientific Meeting of the Australian and New Zealand Society of Nuclear Medicine (ANZSNM ASM 2025), to be held in Melbourne, Australia from 23–25 May 2025....Demonstrating its commitment to development and education in theranostics, Telix presentations include: ProstACT Global Phase 3 study of TLX591 (177Lu-rosopatamab tetraxetan), Telix's first-in-class PSMA targeting radio antibody-drug conjugate (rADC) therapy candidate; STARSTRUCK study of TLX250 (177Lu-girentuximab) in combination with peposertib in patients with carbonic anhydrase IX (CAIX)-expressing solid tumors, and a preclinical evaluation of 225Ac-girentuximab in combination with DNA damage response inhibition..."

Clinical data • Preclinical • Castration-Resistant Prostate Cancer

Enhanced radiation therapy outcomes via TGF? inhibition in the tumor microenvironment using bifunctional antibody TLX250-TRAP (ESTRO 2025) - "These findings establish that TLX250-TRAP targets TAA and inhibits TGFβ downstream signaling. They also provide evidence of enhanced therapeutic outcomes when combined with EBRT and anti-PDL1 immune checkpoint inhibition. Therapeutic isotope labeling of TLX250-TRAP shows promising anti-cancer potential through antigen- specific delivery of radiation to tumors combined with TGFβ neutralization."

Biomarker • Tumor microenvironment • Breast Cancer • Hepatology • Oncology • Solid Tumor • CA9

Cost-Effectiveness Analysis of 89-Zr-Girentuximab PET—CT (TLX250) to Guide Management of Small Renal Masses (AUA 2025) - "The use of TLX250 alone is the most cost-effective strategy across a variation of costs and probabilities. TLX250 with reflex RMB for negative scans helps avoid unnecessary treatment of benign SRMs and minimizes risks of untreated malignant SRMs and can be cost effective compared to RMB and empiric PN."

Cost effectiveness • HEOR • Oncology • Solid Tumor

Preclinical and Clinical Feasibility Studies as the First Step Before Forthcoming Intravesical Instillation of [211At]At-anti-CA-IX Antibody (ATO-101™) Study in Patients with Non-Muscle-Invasive Bladder Cancer Unresponsive to Standard of Care. (PubMed, Cancers (Basel)) - "Preclinical and clinical data demonstrate the promising therapeutic role of 211At-targeted alpha agents in NMIBC, and the [211At]At-anti-CA-IX antibody (ATO-101™) could fulfill this role. A phase I FIH clinical trial is in preparation, and results are expected within the next years."

Journal • Preclinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CA9

Investor Webinar: Telix Therapeutics Urology Showcase and Expert Forum (GlobeNewswire) - "In this education session, Telix and global key opinion leaders will provide an overview on the development of its therapeutic candidates in prostate and kidney cancers: Neeraj Agarwal, MD...will discuss the ProstACT Global Phase 3 trial of TLX591 (177Lu rosopatamab tetraxetan), Telix’s lead radio antibody-drug conjugate (rADC) therapy candidate in prostate cancer; Eric Jonasch, MD...will discuss the STARLITE studies of TLX250 (177Lu girentuximab) in combination with immunotherapy, in clear cell renal cell carcinoma; Rodney Hicks, MD...will discuss TLX592 (64Cu/225Ac RADmAb) and the role of targeted alpha therapies in the treatment of prostate cancer."

Clinical • Genito-urinary Cancer • Prostate Cancer • Renal Cell Carcinoma

Phase Ib/II trial of 177Lu-girentuximab, cabozantinib and nivolumab in aRCC (YouTube) - "Eric Jonasch, MD...provides an overview of a phase Ib/II study (NCT05663710) assessing 177Lu-girentuximab with cabozantinib and nivolumab in treatment-naïve advanced clear cell renal cell carcinoma (aRCC). By leveraging targeted radiation to enhance T cell activity, this approach aims to improve complete response rates beyond current immunotherapy standards."

Video • Renal Cell Carcinoma

Telix to Showcase Urology Pipeline at Upcoming ASCO Genitourinary Cancers Symposium (ASCO GU 2025) (GlobeNewswire) - "Telix Pharmaceuticals Limited...today announces presentations featuring the Company’s late-stage and next generation therapeutic programs at the upcoming American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU 2025) to be held in San Francisco, CA (US) from 13 – 15 February 2025...'For the first time at a medical congress, preliminary data will be presented from the CUPID study of TLX592, which was successful in demonstrating clinical proof-of-concept of Telix’s alpha therapy candidate for prostate cancer.' ProstACT GLOBAL, the first Phase 3 trial to evaluate Telix’s lead rADC therapy candidate, TLX591...will be highlighted during a ‘Trials In Progress’ presentation. In kidney cancer, Principal Investigators of the STARLITE-1 and -2 investigator-initiated trials will provide an update on design and status of these trials in progress."

P1 data • Trial status • Castration-Resistant Prostate Cancer • Kidney Cancer • Prostate Cancer

ASCO GU 2025: STARLITE 2: Phase 2 Study of Nivolumab Plus 177lutetium-Labeled Anti–Carbonic Anhydrase IX (CAIX) Monoclonal Antibody Girentuximab (177Lu-Girentuximab) in Patients With Advanced Clear Cell Renal Cell Carcinoma (ccRCC) (UroToday) - "The STARLITE 2 trial is a phase 2, open-label, single-arm study evaluating the combination of lutetium-177 (¹⁷⁷Lu)-girentuximab and nivolumab in patients with previously treated clear cell renal cell carcinoma (ccRCC)....Treatment consists of 28-day cycles. C1D1 is the date of the first 177Lu-girentuximab dose, with subsequent doses administered q12-14 weeks (e.g., C4D1 and C7D1) for a maximum of three doses. Dose 2 of 177Lu-girentuximab is 75% of Dose 1, and Dose 3 is 75% of Dose 2. Nivolumab 240 mg is given on D1 and D15 of all cycles except C1D1, where the first nivolumab dose is administered on C1D15. Starting with C10, nivolumab may be switched to 480 mg q4 weeks. When nivolumab and 177Lu-girentuximab are given on the same day (e.g., C7D1), nivolumab is administered first."

Clinical protocol • Clear Cell Renal Cell Carcinoma

ASCO GU 2025: Phase 1b/2 Study of Combination 177Lu Girentuximab + Cabozantinib and Nivolumab in Treatment Naive Patients With Advanced Clear Cell RCC (UroToday) - "The 2025 GU ASCO annual meeting featured a kidney cancer trials in progress session and a presentation by Dr. Eric Jonasch discussing a phase 1b/2 study of combination 177Lu girentuximab + cabozantinib and nivolumab in treatment naive patients with advanced clear cell RCC....This single arm phase 1b/2 study will test the hypothesis that adding 177Lu-girentuximab to cabozantinib and nivolumab will increase the complete response rate when compared to historical outcomes with nivolumab + cabozantinib. The primary objective is to determine the safety and complete response rate of this treatment option in previously untreated clear cell RCC patients. 177Lu-girentuximab 1480 MBq/m2 (61% of single agent maximum tolerated dose) will be administered every 12 weeks for up to 3 cycles. Starting with the second cycle, nivolumab and cabozantinib will be added at standard dose."

Trial status • Clear Cell Renal Cell Carcinoma

DNA-Dependent Protein Kinase Inhibitor Peposertib Enhances Efficacy of 177Lu-Based Radioimmunotherapy in Preclinical Models of Prostate and Renal Cell Carcinoma. (PubMed, J Nucl Med) - " 177Lu-DOTA-girentuximab (targeting carbonic anhydrase IX) or 177Lu-DOTA-rosopatamab (targeting prostate-specific membrane antigen) was used to deliver β-radiation to tumors via a single intravenous dose (3 or 6 MBq) in mice bearing SK-RC-52 RCC or LNCaP prostate cancer xenografts, respectively. Our findings suggest a synergistic effect between peposertib and 177Lu-based radioimmunotherapy, wherein peposertib enhanced the efficacy of radioimmunotherapy. This synergy indicates the potential to reduce the necessary dose of radioimmunotherapy for effective cancer treatment."

Journal • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • CA9

A BLA has been submitted to the FDA for the use of TLX250-CDx kidney cancer imaging, an investigational PET drug product for the non-invasive diagnosis and characterization of clear cell renal cell carcinoma. #kicsm | @KidneyCancerDoc

Renal Cell Carcinoma

Developer Submits BLA for TLX250-CDx Kidney Cancer Imaging in ccRCC (Cancer Network) - "'[TLX250-CDx] PET-CT imaging accurately identified [ccRCC] in patients with a cT1 [IRM of 7 cm or less], with a favorable safety profile,' lead ZIRCON study author Brian M Shuch, MD...wrote in a paper published in Lancet Oncology. 'These results establish the value of [TLX250-CDx] PET-CT imaging as a new standard, non-invasive tool for the diagnosis and detection, characterization, and differentiation of ccRCCfrom other renal and extrarenal lesions in clinical practice, minimizing the risk of unnecessary invasive interventions.'"

Media quote • Renal Cell Carcinoma

Eric Jonasch, MD, on phase 1/2 trial of 177Lu-girentuximab combination in ccRCC (Urology Times) - "'We really want to understand whether by using this beta emitter, together with the combination of cabazantinib and the nivolumab, we're getting better outcomes than we would expect with the doublet alone,' says Eric Jonasch, MD."

Video • Renal Cell Carcinoma

SUO 2024: Phase 1B/2 Study of Combination 177Lu Girentuximab + Cabozantinib and Nivolumab in Treatment Naïve Patients with Advanced Clear Cell RCC (UroToday) - "This single arm phase 1b/2 study will test the hypothesis that adding 177Lu-girentuximab to cabozantinib and nivolumab will increase the complete response rate when compared to historical outcomes with nivolumab + cabozantinib....A 5 patient safety lead-in will evaluate myelosuppression. Ongoing safety and futility monitoring will employ a Bayesian approach. The sample size was chosen for reasonable operating characteristics to distinguish a complete response rate (primary endpoint) of 18% as better than 9% using a beta (0.09, 0.91) prior. Secondary endpoints are objective response rate, progression free survival by RECIST 1.1, and overall survival. To explore the effects of the treatment on inducing activated T cell infiltration, patients will undergo pre/post-treatment PET scan with 18F-AraG radiotracer as well as biopsies for single cell, spatial transcriptomics, and proteomics studies."

Clinical protocol • Clear Cell Renal Cell Carcinoma