Rencarex (girentuximab)

There will be significant change in the field of imaging in RCC as molecular imaging becomes increasingly popular, which reflects a shift in management to a more conservative approach, especially for small renal masses (SRMs). There is the hope that the improvement in imaging will result in less unnecessary invasive surgeries or biopsies being performed for benign or indolent renal lesions.

Our results suggest that [89Zr]Zr-girentuximab PET-CT has a favourable safety profile and is a highly accurate, non-invasive imaging modality for the detection and characterisation of clear-cell renal cell carcinoma, which has the potential to be practice changing.

On the other end of the spectrum, carbonic anhydrase IX agents, most notably the monoclonal antibody girentuximab - which can be labeled with positron emission tomography radionuclides such as zirconium-89 - are effective at identifying renal masses that are likely to be aggressive clear cell renal cell carcinomas...The combination of molecular imaging and biopsy in selected patients with other advanced imaging methods, such as artificial intelligence/machine learning and the abstraction of radiomics features, offers the optimal way forward for maximization of the information to be gained from risk stratification of indeterminate renal masses. With the proper application of those methods, inappropriately aggressive therapy for benign and indolent renal masses may be curtailed.

This study demonstrates that [89Zr]Zr-DFO-girentuximab administered to Japanese patients with suspected RCC has a favorable safety profile and is well tolerated and has a similar dosimetry profile to previously studied populations.

P=N/A, N=17, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

Our results suggest that post-nephrectomy RCC patients with sarcomatoid differentiation and high PD-L1 expression were more responsive to ICIs. Furthermore, pembrolizumab monotherapy exhibited superior DFS and OS results over other adjuvant therapies.

This new H2MacropaSqOEt chelator was used to modify a monoclonal antibody, girentuximab (hG250), that binds to carbonic anhydrase IX, an enzyme that is overexpressed on the surface of cancers such as clear cell renal cell carcinoma...Evaluation of [225Ac]Ac(MacropaSq-hG250) in a mouse xenograft model, that overexpresses carbonic anhydrase IX, demonstrated a highly significant therapeutic response. It is likely that H2MacropaSqOEt could be used to modify other antibodies providing a readily adaptable platform for other actinium-225 based therapeutics.

P1/2, N=100, Active, not recruiting, M.D. Anderson Cancer Center | Suspended --> Active, not recruiting | Phase classification: P2 --> P1/2

P2, N=100, Suspended, M.D. Anderson Cancer Center | Recruiting --> Suspended

P2, N=100, Recruiting, M.D. Anderson Cancer Center | Phase classification: P1b/2 --> P2

The combination of nivolumab plus cabozantinib was recently approved for the first-line treatment of ccRCC based on the CheckMate 9ER phase 3 study demonstrating improved progression-free survival (PFS) & 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 [18F]F-AraG radiotracer as well as biopsies for single cell, spatial transcriptomics and proteomics studies. Clinical trial information: NCT05239533.

These findings suggest that S100P could serve as a promising biomarker for immunosuppressive microenvironment, which may provide a novel therapeutic way for pancreatic cancer.

P1b/2, N=100, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: May 2024 --> Jun 2023

P1b/2, N=100, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: May 2023 --> May 2024

No abstract available

No abstract available

Additionally, newer modalities, such as contrast-enhanced ultrasound, dual energy computed tomography, and molecular imaging, will be discussed in conjunction with emerging radiomics and artificial intelligence techniques. Current diagnostic algorithms combined with newer approaches may be an effective way to overcome existing limitations in renal mass and RCC characterization.

P=N/A, N=17, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2023 --> Apr 2024 | Trial primary completion date: Apr 2023 --> Apr 2024

Coprimary objectives were to evaluate both the sensitivity and specificity of TLX250-CDx PET/CT imaging in detecting ccRCC in patients with IDRM, using histology as standard of truth. 89 Zr-DFO-girentuximab PET/CT is well tolerated and can accurately and noninvasively identify and characterize IDRMs, showing promising utility for guiding surgical and treatment decisions.

P2, N=12, Recruiting, Institut Cancerologie de l'Ouest | Trial completion date: Dec 2022 --> Jun 2024 | Trial primary completion date: Dec 2022 --> Mar 2024

P1, N=6, Completed, Institut Cancerologie de l'Ouest | Recruiting --> Completed

The trial is currently accruing to the safety lead-in phase. Clinical trial information: NCT05239533.

89Zr-DFO-girentuximab (hereafter referred to as TLX250-CDx) is a diagnostic radiopharmaceutical for PET imaging that targets CAIX and has demonstrated clinical success in ccRCC imaging. Statistics will be descriptive with no formal hypothesis. The study is ongoing.

P3, N=252, Active, not recruiting, Telix International Pty Ltd | Recruiting --> Active, not recruiting | Trial completion date: May 2022 --> May 2023 | Trial primary completion date: Dec 2021 --> Dec 2022

Enhanced therapeutic efficacy was achieved when two agents ([Lu]Lu-cG250 RIT and sunitinib) that on their own did not induce satisfactory response levels, are combined. Our findings provide a promising new therapeutic strategy for patients with advanced RCC.

In addition, whole body planar and SPECT imaging are performed after each 177Lu-girentuximab dose to evaluate distribution, lesion uptake and dosimetry of 177Lu-girentuximab. The trial is currently accruing to the safety lead-in phase.

Results : We included thirteen studies with the following adjuvant therapies: Axitinib, Girentuximab, interferon-alpha, interleukin-2, Pazopanib, Pembrolizumab, Sorafenib, Sunitinib and Thalidomide. Conclusions : Pembrolizumab and pazopanib were the only two adjuvant agents that improved time to disease recurrence compared to observation, with the former likely being the most efficacious. None of the treatments improved overall survival and almost all increased severe adverse events.

P1, N=6, Recruiting, Institut Cancerologie de l'Ouest | Not yet recruiting --> Recruiting

P2, N=12, Recruiting, Institut Cancerologie de l'Ouest | Trial completion date: Aug 2021 --> Dec 2022 | Initiation date: May 2021 --> Sep 2021 | Trial primary completion date: Aug 2021 --> Dec 2022

P1, N=20, Recruiting, South Metropolitan Health Service

Atovaquone decreased CAIX expression only in the FaDu tumor model. [In]-girentuximab-F(ab') specifically targets CAIX-expressing areas in HNSCC xenografts, but differences in vessel density and necrosis most likely affected tracer uptake in the tumors and therefore complicated quantification of changes in CAIX expression.

P1, N=6, Completed, Telix International Pty Ltd | Recruiting --> Completed | Phase classification: P1/2 --> P1 | N=40 --> 6 | Trial completion date: Aug 2021 --> Apr 2021 | Trial primary completion date: Jun 2021 --> Oct 2020

P1/2, N=12, Recruiting, Telix International Pty Ltd

P3, N=252, Recruiting, Telix International Pty Ltd | Trial completion date: Oct 2021 --> May 2022 | Trial primary completion date: May 2021 --> Dec 2021

89Zr-girentuximab PET/CT has the ability to diagnose ccRCC in localized disease. In metastatic disease, it enables the differentiation of ccRCC from non-ccRCC cancers and the evaluation of disease extent. 89Zr-girentuximab PET/CT diagnostic accuracy is currently evaluated in a multicenter phase III trial.

P1, N=6, Not yet recruiting, Institut Cancerologie de l'Ouest

P2, N=12, Recruiting, Institut Cancerologie de l'Ouest | Not yet recruiting --> Recruiting

P2, N=12, Not yet recruiting, Institut Cancerologie de l'Ouest

P3, N=252, Recruiting, Telix International Pty Ltd | Trial completion date: Jun 2021 --> Oct 2021 | Trial primary completion date: Dec 2020 --> May 2021

P1/2, N=40, Recruiting, Telix International Pty Ltd

Radioimmunotherapy (RIT) with cG250, an antibody recognizing the ccRCC-associated antigen CAIX, labelled with the beta emitter 177Lu has demonstrated efficacy in patients with metastasized ccRCC but haematotoxicity hindered clinical implementation... These results highlight the potential of targeting alpha-emitters as a treatment modality and suggest that 225Ac-hG250 may offer a promising therapeutic approach in ccRCC. Further optimization studies to prevent nephrotoxicity are ongoing.