Positive results from cohort 1 of cisplatin-eligible patients in the pivotal Phase II TROPHY U-01 study of sacituzumab govitecan-hziy (Trodelvy®; Immunomedics), a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38), in the treatment of patients with metastatic urothelial cancer (mUC) confirm earlier interim findings and prior Phase I/II study results demonstrating that sacituzumab govitecan has significant activity and is safe in patients with heavily-pretreated mUC who progressed on both platinum-based chemotherapy and checkpoint inhibitors (CPI).[1]

The data presented European Society for Medical Oncology (ESMO) Virtual Congress 2020 demonstrates that sacituzumab govitecan achieved an overall response rate (ORR) of 27% (n = 31; 95% CI, 19%-37%), which meant that the study met the primary endpoints of the trial. The study results also showed a complete response (CR) rate of 5% (n = 6), which was based on a blinded independent central assessment per RECIST v1.1. Study data also showed a partial response (PR) of 22% (n = 25). Ths study also demonstrated a median duration of response (DoR) 5.9-month ((95% CI, 4.70-8.60) in heavily-pretreated patients with metastatic urothelial cancer (mUC).

As of data cutoff on May 18, 2020, eight of the 31 responders have an ongoing response and remain on treatment. Sacituzumab govitecan has received Fast Track Designation from the U.S. Food and Drug Administration (FDA) in this indication.

“Given that only about 10% of patients with mUC who have cancer progression after platinum-based and CPI therapy are expected to respond to single-agent chemotherapy with approximately two to three months of median progression-free survival, today’s compelling results with sacituzumab govitecan offer patients and families new hope,” noted Yohann Loriot, M.D., Ph.D., Institut de Cancérologie Gustave Roussy, Villejuif, France, who gave the late-breaking oral presentation of the pivotal study at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

“We believe that sacituzumab govitecan may offer a new treatment option for patients with mUC based on the successful data readout today,” remarkedLoretta M. Itri, M.D., Chief Medical Officer of Immunomedics.

“While we are seeking guidance from the FDA on the registrational pathway, the new Phase III TROPiCS-04 study in third-line mUC has been reviewed by FDA, is under review by the European Medicines Agency, and is currently in the initiation phase,” Itri noted.

Summary of the results for cohort 1 of TROPHY U-01.

Safety profile
Sacituzumab govitecan continued to demonstrate a tolerable and predictable safety profile consistent with previous observations in mUC and other tumor types. Treatment-related Grade 3 and 4 adverse events were mostly hematologic and gastrointestinal related, including neutropenia (34%) and diarrhea (10%). Seven patients (6%) discontinued treatment due to adverse events, three of whom due to neutropenia or its complications. There was one treatment-related death from sepsis due to febrile neutropenia. There were no grade 2 or above events of neuropathy or rash, and no cases of interstitial lung disease reported.

Clinical trials
Phase II Open-label, Study of IMMU-132 in Metastatic Urothelial Cancer – NCT03547973
Study of Sacituzumab Govitecan (IMMU-132) in Metastatic or Locally Advanced Unresectable Urothelial Cancer (TROPiCS-04) – NCT04527991

Highlights of prescribing information
Sacituzumab govitecan-hziy (Trodelvy®; Immunimedics)[Prescribing Information]

National Drug Code List
NDC CODE: 55135-132 [Package Description]

References
[1] Syed YY. Sacituzumab Govitecan: First Approval. Drugs. 2020;80(10):1019-1025. doi:10.1007/s40265-020-01337-5

Note
An edited version of this article was published in ADC Review | Journal of Antibody-drug Conjugates.

Featured image: ESMO 2012. Photo courtesy: © 2016 – 2020  European Society for Medical Oncology. Used with permission.

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