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Genitourinary Research With Ben Garmezy, MD

Oncology / Hematology

Dr. Garmezy joined Sarah Cannon Research Institute (SCRI) in 2021 and serves as the Associate Director of Genitourinary Research. In his role, Dr. Garmezy oversees investigational therapy trials, as well as standard of care treatments, for GU cancers, including prostate, kidney, bladder, and testicular cancers.

TROP2 ADCs in Urothelial Carcinoma: Where Do We Go From Here?

Dear readers,

At the Uromigos Live & Unplugged 2024 event, Drs. Powles, Apolo, Grivas, Gupta, and Sridhar discussed the role of Sacituzumab govitecan (SG) in urothelial carcinoma. SG is a Trop2 Antibody Drug Conjugate (ADC) that has been FDA-approved since 2021 for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who previously received platinum-containing chemotherapy and a PD-1/PD-L1 inhibitor. The landscape for the treatment of mUC has evolved rapidly since that time. Currently, many patients in the US are receiving the combination of Enfortumab Vedotin (EV, Nectin-4 ADC) + Pembrolizumab (P) in the front-line setting. While there is high-quality evidence for Cisplatin + Gemcitabine + Nivolumab in cis-eligible patients as well, it’s hard to argue with the data for EV + P as a front-line option for the majority of patients.

The question is: what do we do after EV + P? Some patients will go on to get doublet chemotherapy with Platinum + Gemcitabine. However, many patients will not be fit for this combination at the time of progression. In patients who are FGFR-positive, Erdafitinib can be used. Otherwise, SG vs Single Agent Taxane were the remaining options. A press release for TROPICS-04 recently reported that the primary endpoint was not met for SG vs Single Agent Chemo in the post Platinum and Immunotherapy space. This has led to the voluntary withdrawal of SG’s accelerated approval. This leaves very limited options for patients post EV + P.

I think the Uromigos roundtable provides great insight about how Trop2 ADCs can provide future benefits to our patients. Is it an upfront combination approach such as Nectin-4 ADC + Trop2 ADC + PD1 inhibitor in the front line setting (such as the DAD study presented by Dr. McGregor)? Can a novel Trop2 ADC provide a better efficacy vs toxicity signal and get an approval in the subsequent line space? A few Trop2 ADCs are in development currently.

Many questions remain, but finding novel targets and therapeutic modalities in mUC is essential.

Best,

Ben Garmezy, MD

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