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Molecular Analyses of Sacituzumab Govitecan in Urothelial Carcinoma With Manoj Bupathi, MD

At the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Oncology Data Advisor sat down with Manojkumar Bupathi, MD, MS, a Genitourinary (GU) Medical Oncologist at Sarah Cannon Research Institute and Rocky Mountain Cancer Centers, to talk about his two studies he is presenting this year about the efficacy and safety of sacituzumab govitecan (SG) in urothelial cancer.  

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we're here at the ASCO Annual Meeting, and I'm joined by Dr. Manoj Bupathi. Thanks so much for coming on today.

Manojkumar Bupathi, MD, MS: Thank you for having me.

Oncology Data Advisor: Would you like to introduce yourself and share what your work focuses on?

Dr. Bupathi: My name is Manoj Bupathi. I'm a GU Medical Oncologist at Sarah Cannon Research Institute and Rocky Mountain Cancer Centers in Denver, Colorado. I do a lot of work in early phase studies, from phase 1 to phase 3, focused on all GU tumors.

Oncology Data Advisor: I believe you have two studies here about sacituzumab govitecan in urothelial cancer. One is about the safety analysis by UGT1A1 status. Would you like to give some background about this study and what the role of UGT1A1 is in urothelial cancer?

Dr. Bupathi: Yes. Sacituzumab has been looked at in advanced urothelial carcinoma and has been shown to be helpful in patients who are refractory to other treatment options. So, it has been looked at in a number of cohorts. There have been three cohorts which we've evaluated so far, and it showed an objective response rate in the first cohort of around 28%. In the second cohort it was 32%, and the third cohort was an 41% overall response rate (ORR).

TROP2 is where sacituzumab is targeting, and it was given an accelerated approval post-chemotherapy and post-immunotherapy. And here in the UGT1A1 abstract, what we were looking at was the patients in Cohort 1, and we were looking to see if there were any safety outcomes that can change based on the UGT1A1 status. In this cohort, patients had received sacituzumab on Day 1 and Day 8, and after a medium follow-up of 10.5 months, we found that the incidences of diarrhea—any-grade related diarrhea—and neutropenia, as well as significant grade 3 diarrhea, grade 3 neutropenia, and grade 3 anemia were all the same regardless of the UGT1A1 status.

Basically, it tells us that with the longer follow-up, the safety profile was consistent with what was known before. And the status of the UGT1A1 did not impact the tolerance or interruptions, or anything like that. It did seem like the incidence of UGT1A1 in patients who had homozygous status was slightly more frequent, but otherwise no other new safety signals.

Oncology Data Advisor: That's great. Will this knowledge be used to impact how sacituzumab is used for patients?

Dr. Bupathi: I don't think it changes how we use it at the present time. I think we have to do some additional safety analysis to figure that out.

Oncology Data Advisor: Great. Moving on to your other study, you also have the efficacy of sacituzumab govitecan and urothelial carcinoma (UC) by TROP2 expression. Would like to give us some background about this study as well?

Dr. Bupathi: Yes. So, similarly, sacituzumab is a drug that is a TROP2-directed antibody-drug conjugate (ADC). TROP2 is a transmembrane glycoprotein and it's elevated in many cancers. Similarly, it's elevated in expression at urothelial carcinoma. And so here what we looked at was assessing the outcomes for Cohort 1, 2, and 3 that we've previously reported by TROP2 based on archival tumor expression.

And what we found is that when you assess this TROP2 expression using an immunohistochemistry (IHC) stain, the idea was that the TROP2 association with clinical end points can be used to see if there's a change in ORR. And what we found is that of the 192 patients who were all enrolled in Cohorts 1 to 3, 144 patients had samples that were evaluable for TROP2 and 139 were evaluable for efficacy analysis of TROP2 expression.

And really what we found is that there was no difference when you look at this in terms of outcomes. So similar outcomes were seen whether you had a high expression or not. And when we had looked at Cohort 1 versus Cohort 2 and 3, it was all the same. So, there was no real difference in what we find, and it really suggests that the activity of SG may be independent of the TROP2 expression.

Oncology Data Advisor: Do you have any other additional analyses underway regarding the efficacy of SG in different populations?

Dr. Bupathi: We're looking at efficacy of SG across various subtypes and eligibility. So, we're looking at SG in patients who are cisplatin-ineligible and receive SG in conjunction with immunotherapy, whether it be a programmed cell death protein 1 (PD-1) plus a TIGIT in combination, as well as in the maintenance therapy and using SG in combination with immunotherapy. So, more data is yet to become. There are a total of six cohorts on this study, only of which three are being evaluated so far. And we have three more that we're starting to look at.

Oncology Data Advisor: Great. Well, that's really great to know. Thank you so much for stopping by to talk about this today.

Dr. Bupathi: Thank you for having me.

About Dr. Bupathi

Manojkumar Bupathi, MD, MS, is a Genitourinary Medical Oncologist at Sarah Cannon Research Institute and Rocky Mountain Cancer Centers in Denver, Colorado. His expertise is with genitourinary and breast cancers, specifically with solid tumors. Dr. Bupathi is passionate about personalizing his care routine with each of his patients to meet their specific needs and communication effectively.

For More Information

Loriot Y, Petrylak D, Rezazadeh A, et al (2023). Safety analysis by UGT1A1 status of TROPHY-U-01 cohort 1, a phase 2 study of sacituzumab govitecan (SG) in patients (pts) with metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023. J Clin Oncol 41(suppl 16). Abstract 4514. DOI:10.1200/JCO.2023.41.16_suppl.4514

Loriot Y, Balar A, Petrylak D, et al (2023). Efficacy of sacituzumab govitecan (SG) in locally advanced (LA) or metastatic urothelial cancer (mUC) by trophoblast cell surface antigen 2 (Trop-2) expression. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023. J Clin Oncol 41(suppl 16). Abstract 4579. DOI:10.1200/JCO.2023.41.16_suppl.4579

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.


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