Rencarex (girentuximab)

Comparison of the two most water-soluble chelators from the set of DFO, DFO* and D8W, showed that compared to [89Zr]Zr-DFO-mAb (mAb = Girentuximab), [89Zr]Zr-D8W-mAb had improved 89Zr radiolabeling kinetics and in vitro stability. Key to its utility, bone deposition of 89Zr was lower for [89Zr]Zr-D8W-mAb than [89Zr]Zr-DFO-mAb, as assessed by PET imaging in a CAIX-expressing HT-29 tumor-bearing Balb/C nude mouse model. The performance of D8W coupled with its water solubility supports its merit in its use in 89Zr-immunoPET agents.

The iridium(iii)-girentuximab conjugate described here could be of use for emissive detection of carbonic anhydrase IX positive tumour tissue to guide surgical resection as well as carbonic anhydrase IX targeted photodynamic therapy. The approach described here could be used with other tumour targeting antibodies.

P1, N=24, Not yet recruiting, Institut Cancerologie de l'Ouest

[89Zr]Zr-girentuximab PET/CT is a sensitive imaging method and offers promise for novel theranostics for mTNBC patients.

A recent phase III trial (ZIRCON) is widely believed to have laid the groundwork for United States Food and Drug Administration approval of the CAIX monoclonal antibody 89Zr-girentuximab...Further, emerging new targeted radiotracers and techniques such as imaging biomarker discovery with artificial intelligence will bolster those concepts. In this manual, we synthesize key data into a recommended approach.

P1/2, N=100, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Oct 2025 --> Oct 2027

The use of SLNB has transformed nodal staging in PeC, influencing treatment decisions and reducing morbidity in patients undergoing surgery. In other urological malignancies, it has not yet established itself as a standard tool for nodal staging. Its impact on survival, quality of life, and translational research remains to be determined.

P=N/A, N=17, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Apr 2025 --> Apr 2026

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.

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.

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.

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.