Daniel P. Petrylak, MD, Details Data From TROPHY U-01 Study in Previously Treated Metastatic Urothelial Carcinoma

Daniel P. Petrylak, MD, spoke with CancerNetwork® about the results of the TROPHY U-01 study examining sacituzumab govitecan in the treatment of patients with metastatic urothelial carcinoma following failure of platinum-based chemotherapy.

Daniel P. Petrylak, MD, professor of medicine (medical oncology) and urology at the Yale Cancer Center, spoke with CancerNetwork® about the phase 2 TROPHY U-01 study (NCT03547973) investigating the potential of sacituzumab govitecan (Troldevy) as a treatment for patients with metastatic urothelial carcinoma who had progressed on platinum-based chemotherapy.

The multicohort study comprised several treatment arms, including a group of 113 patients with locally advanced or unresectable metastatic urothelial carcinoma who had progressive disease following platinum-based combination chemotherapy and checkpoint inhibitors who were enrolled to cohort 1.1 Data from this subset showed that sacituzumab govitecan had notable efficacy and a manageable safety profile in this population of patients and subsequently supported an accelerated approval from the FDA in this setting.2

“This has been an area where we had a lack of drugs and we now have several drugs that are approved by the FDA—specifically 2 that are approved—and sacituzumab [govitecan] is one of those,” Petrylak explained in his conversation with CancerNetwork®.

CancerNetwork®: Could you start by reviewing the mechanism of action of sacituzumab govitecan and the rationale for this phase 2 study?

PETRYLAK: TROP-2 is an antigen that’s expressed in a variety of different solid tumors, including urothelial carcinoma and breast cancer. There has been an antibody-drug conjugate that has been raised against TROP-2 that delivers a chemotherapeutic agent, SN-38, directly to the urothelial carcinoma cells. This is, of course, antibody-drug conjugates, [which are] a technology that has been used in bladder cancers, bones, and other solid tumors. The purpose of this trial was to replicate and confirm the phase 1 data that [were obtained] with sacituzumab [govitecan] in patients with metastatic urothelial carcinoma.

Could you talk about the patient population examined in this research? What were some of the key eligibility criteria?

This was a phase 2 trial [where] patients in the study were permitted to have prior chemotherapy in cohort 1. The TROPHY U-01 study had 2 different cohorts. Cohort 1 were patients who had progressed after platinum-based chemotherapy and an anti–PD-1 or –PD-L1 [agent]. Cohort 2 was a small cohort of 40 patients, who were ineligible to receive platinum-based therapy and progressed after PD-1 or PD-L1 [inhibitors].

Could you talk about the efficacy data that stood out to you?

In the paper that [was published in the Journal of Clinical Oncology regarding] cohort 1, 113 patients were entered with a median follow up of 9.1 months. The objective response rate, which was the primary end point, was 27% [95% CI, 19.5%-36.6%]. The median duration of response was 7.2 months [95% CI, 4.7-8.6], and the median progression-free survival was 5.4 months [95% CI, 3.5-7.2]. Some of the key treatment-related adverse events were neutropenia, leukopenia, anemia, diarrhea, and febrile neutropenia.

What are the implications for these results, and what can you take away from it?

Basically, that you can engender responses in patients with further refractory urothelial carcinoma. This has been an area where we had a lack of drugs, and we now have several drugs that are approved by the FDA—specifically 2 that are approved—and sacituzumab [govitecan] is one of those. We have enfortumab vedotin (Padcev) that has [received] full approval by the FDA for third-line therapy.3 We also have erdafitinib (Balversa), which is an FGFR-specific drug. That’s approved for those patients with the FGFR mutation, either who are platinum ineligible or for patients who have had prior chemotherapy. This is another treatment that we have out there that we can potentially use.

Looking ahead, do you have plans for the phase 3 part of this research? What comes next to build off this data?

Phase 3 [is planned] for full approval. TROPiCS-04 [NCT04527991] is going to be sacituzumab [govitecan] versus physician’s choice [of chemotherapy] in patients with locally advanced metastatic urothelial carcinoma. That’s a phase 3 trial that’s going to hopefully confirm the data, with the primary end point being overall survival.


  1. Tagawa ST, Balar AV, Petrylak DP, et al. TROPHY-U-01: A phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors. J Clin Oncol. 2021;39(22):2474-2485. doi:10.1200/JCO.20.03489
  2. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. News release. FDA. April 13, 2021. Accessed October 28, 2021. https://tinyurl.com/amp5fdrm
  3. FDA grants regular approval to enfortumab vedotin-ejfv for locally advanced or metastatic urothelial cancer. News release. FDA. July 9, 2021. Accessed October 28, 2021. https://tinyurl.com/c67mt9fr
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