Rencarex (girentuximab) / Heidelberg Pharma, Esteve, Merck (MSD) - LARVOL DELTA

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

Enhanced Antitumor Efficacy of DNA Damage Response Inhibitors Combined with 225Ac-DOTA-girentuximab (SNMMI 2025) - "Lartesertib and peposertib exhibited IC50 values of 3.543 µM and 0.7712 µM, respectively, in SK-RC-52 cells. The IC50 value for 225Ac-DOTA-girentxuimab in SK-RC-52 cells was 0.1505 kBq/mL. Synergy mapping analysis revealed an additive effect between 225Ac-DOTA-girentuximab and lartesertib."

Clinical • Ataxia • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • CA9

Comprehensive PET Imaging Strategies for Enhanced Diagnosis and Prognostic Assessment in Clear Cell Renal Cell Carcinoma (ccRCC): A Multi-Tracer Approach (SNMMI 2025) - " We reviewed the clinical applications and diagnostic performance of multiple PET tracers used in ccRCC management, including 18F-FDG, 68Ga- or 18F-PSMA, 68Ga-FAPI, 89Zr-DFO-Girentuximab, 68Ga-Pentixafor, and 68Ga-NYM046 PET/CT... 18F-FDG PET/CT: FDG PET/CT, limited in detecting primary renal lesions due to renal excretion, excels in staging, restaging, and recurrence detection in ccRCC patients. It outperforms conventional imaging in monitoring therapeutic response and metastasis. FDG PET/CT can differentiate tumor thrombus from blood clots, providing prognostic value."

Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Infectious Disease • Oncology • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Thrombosis • CA9 • CXCR4 • FAP • FOLH1

PET Immune system imaging with 89Zr. (SNMMI 2025) - "Introduction: Zirconium-89 (89Zr) is a radioactive isotope in at least 3 clinical trials1 Additionally, the FDA recently approved 89Zr-girentuximab, ZIRCON study on Renal Cell Cancer...Scan time varies due to crystal type, sensitivity, resolution of the scanner. Good Image quality due to low scatter, short positron range, and uptake specificity."

Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8

Use and Quantitation of 89Zr-girentuximab (SNMMI 2025) - "Sponsored by TS"

DIFFERENTIAL DNA METHYLATION IN STEATOTIC LIVER DISEASE-ASSOCIATED HEPATOCELLULAR CARCINOMA (SLD-HCC) (DDW 2025) - "A total of 11 CpG sites (cg07850527, cg25032595, cg05022673, cg20129213, cg15073853, cg18422058, cg21902984, cg07674312, cg02776297, cg13149322, cg22932387) were differentially methylated across HCC tumor tissue, NTB-HCC, and non-HCC SLD liver (Figure 2)...While ten CpG were differentially methylated in HCC tumor tissue, one CpG site in a gene encoding a nuclear protein important in epigenomic regulation was differentially methylated in both background liver tissue from which HCC arose and HCC tumor tissue. Further investigating this "field defect" may improve understanding of the pathogenesis of SLD-HCC and potential biomarkers of SLD-HCC risk."

Epigenetic controller • Colorectal Cancer • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Oncology • Solid Tumor

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). (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT05239533 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CA9

STARLITE 1: Phase 1b/2 Study of Combined 177Lu-Girentuximab plus Cabozantinib and Nivolumab in Treatment-naïve Patients with Advanced Clear-cell Renal Cell Carcinoma. (PubMed, Eur Urol Focus) - "The aim is to activate cGAS-STING-induced antitumor immunity via targeted radioimmunotherapy damage to DNA. If successful, this approach could establish a novel paradigm that combines radiopharmaceuticals with immunotherapy and targeted therapy in ccRCC."

Journal • P1/2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • STING

STARLITE-1: Phase 1b/2 study of combination 177Lu girentuximab plus cabozantinib and nivolumab in treatment naive patients with advanced clear cell RCC. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT05663710 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P1/2 data • Clear Cell Renal Cell Carcinoma • Renal Cell Carcinoma

Evaluate The Utility Of 124I-cG250 for The Early Detection Of Response to Therapy In Patients With Metastatic Renal Cell Carcinoma (clinicaltrials.gov) - P=N/A | N=17 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2025 ➔ Apr 2026 | Trial primary completion date: Apr 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

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

Re: Brian Shuch, Allan J. Pantuck, Jean-Christophe Bernhard, et al. [89Zr]Zr-girentuximab for PET-CT Imaging of Clear-cell Renal Cell Carcinoma: A Prospective, Open-label, Multicentre, Phase 3 Trial. Lancet Oncol 2024;25:1277-87. (PubMed, Eur Urol) - No abstract available

Journal • P3 data • Genito-urinary Cancer • Oncology • Solid Tumor

Antibody-drug conjugates and radioconjugates targeting carbonic anhydrase IX and XII in hypoxic tumors: Bench to clinical applications. (PubMed, Bioorg Chem) - "New approaches based on small molecule inhibitors and monoclonal antibodies such as girentuximab provided encouraging results in preclinical research and clinical trials. These advances highlight the potential of hCA-targeted therapies to improve cancer treatment for hypoxic tumors."

Journal • Review • Oncology • CA9

Effect of LED Irradiation with Different Red-to-Blue Light Ratios on Growth and Functional Compound Accumulations in Spinach (Spinacia oleracea L.) Accessions and Wild Relatives. (PubMed, Plants (Basel)) - "Some critical enzymes in the Gamma-aminobutyric acid (GABA) shunt cycle and the asparagine and glycolysis pathways were suggested as rate-limiting enzymes, which determined the biosynthesis of functional compounds. Among the examined Spinacia accessions, 'CGN09429', 'CGN09511', and the wild S. turkestanica 'CGN25013' were identified as potential breeding materials, while red:blue = 1:1 was determined as the optimal red-to-blue ratio for spinach growth in a closed-cultivation system."

Journal

Phase 1b/2 study of combination 177Lu girentuximab plus cabozantinib and nivolumab in treatment naive patients with advanced clear cell RCC. (ASCO-GU 2025) - P1/2 | "The combination of nivolumab plus cabozantinib was recently approved for first-line treatment of ccRCC, demonstrating improved progression-free survival (PFS) and objective response rate (ORR) in comparison to sunitinib...Starting with the second cycle, nivolumab and cabozantinib will be added at standard dose. 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 • Metastases • P1/2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Renal Cell Carcinoma • CA9

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). (ASCO-GU 2025) - P2 | "In addition, whole body planar and SPECT imaging are performed after each 177Lu-girentuximab dose to evaluate distribution, lesion uptake and dosimetry. The pre-specified number of DLTs was exceeded in cohort 2 such that dosing reverted back to cohort 1, in which accrual is ongoing."

Clinical • IO biomarker • Metastases • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CA9

Initial clinical experience with Zr-Girentuximab PET-CT for evaluation of renal masses in patients with solitary kidneys. (PubMed, Actas Urol Esp (Engl Ed)) - No abstract available

Journal

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

Phase 1b/2 Study of Combination 177Lu Girentuximab Plus Cabozantinib and Nivolumab in Treatment naïve Patients With Advanced Clear Cell RCC (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Recruiting

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

Girentuximab imaging in renal cancer: diamond in the rough or just ZIRCON? (PubMed, Expert Rev Anticancer Ther) - "Despite its strengths, the trial highlights limitations: restricted imaging scope to the abdomen, lack of a cost-effectiveness analysis, concerns over radiation exposure given zirconium-89's 78.4-hour half-life, and the daily scheduling of the examination. Only further studies and time will reveal whether the ZIRCON trial's findings will shine like a diamond or remain akin to zircon - brilliant but constrained in value."

Clinical • Journal • Review • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Relationship between apoptosis gene DNA methylation and fetal growth and development. (PubMed, Gene) - "The DNA methylation levels of BCL-2 and CASP3 genes are associated with fetal growth and development. Additionally, maternal pre-pregnancy BMI and weight gain during pregnancy were found to correlate with BCL-2 methylation, indicating potential epigenetic mechanisms influencing fetal growth."

Journal • BCL2 • CASP3 • CASP8

[89Zr]Zr-girentuximab PET-CT imaging to diagnose, characterize, and differentiate clear-cell renal cell carcinoma. (PubMed, Med) - "In the phase 3 ZIRCON trial, [89Zr]Zr-girentuximab positron emission tomography-computed tomography (PET-CT) detected the presence of clear-cell renal cell carcinoma (ccRCC) with a sensitivity of 86% and a specificity of 87% in patients with an indeterminate renal mass undergoing nephrectomy.1 This imaging technique could be a promising tool that could revolutionize the management of small renal masses (SRMs) and ccRCC."

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

PHASE 1B/2 STUDY OF COMBINATION 177LU GIRENTUXIMAB PLUS CABOZANTINIB AND NIVOLUMAB IN TREATMENT NAIVE PATIENTS WITH ADVANCED CLEAR CELL RCC (SUO 2024) - "The combination of nivolumab plus cabozantinib was recently approved for first-line treatment of ccRCC, demonstrating improved progression-free survival (PFS) and objective response rate (ORR) in comparison to sunitinib...To explore the effects of the treatment on inducing activated T cell infiltration, patients will undergo pre/post-treatment PET scan with 18 F-AraG radiotracer as well as biopsies for single cell, spatial transcriptomics and proteomics studies. "

Clinical • Metastases • P1/2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CA9

Attacking carbonic anhydrase IX as a gateway to remodeling tumor hypoxia (SITC 2024) - "Background Tumor hypoxia impedes T cell infiltration and effector function, rendering hypoxic solid tumors refractory to immune checkpoint blockade (ICB) and predicts poorer outcomes in patients.1 2 Previously, we have shown that the Hypoxia activated prodrug (HAP) TH-302 (evofosfamide) decreases tumor hypoxia and sensitizes murine prostate cancer to ICB.2 While TH-302 decreased tumor hypoxia in responding patients in a phase 1 clinical trial, non-responding patients remained immune to hypoxia reduction and attenuation of tumor proliferation.3 To overcome this limitation, we seek to target the hypoxic tumor microenvironment(TME) agnostic of its proliferation status using Carbonic anhydrase IX (CAIX) binding cytodepletive monoclonal antibodies(mAbs). CAIX is a cell surface enzyme strongly induced under hypoxia and has been correlated with poorer prognosis and ICB resistance.4 5 Lack of murine cross-reactivity amongst existing human CAIX antibodies like Girentuximab has..."

Genito-urinary Cancer • Melanoma • Oncology • Prostate Cancer • Solid Tumor • CA9