The FDA ( U.S. Food and Drug Administration ) has granted accelerated approval of Trodelvy ( Sacituzumab govitecan-hziy; Sacituzumab govitecan ) for use in adult patients with locally advanced or metastatic urothelial cancer ( UC ) who have previously received a Platinum-containing chemotherapy and either a programmed death receptor-1 ( PD-1 ) or a programmed death-ligand 1 ( PD-L1 ) inhibitor.
The accelerated approval was based on data from the international phase 2, single-arm TROPHY study.
Of the 112 patients who were evaluable for efficacy, 27.7% of those treated with Trodelvy responded to treatment, with 5.4% experiencing a complete response and 22.3% experiencing a partial response.
The median duration of response was 7.2 months ( 95% CI: 4.7-8.6 ).
The Trodelvy U.S. Prescribing Information has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea.
Trodelvy’s safety profile in the TROPHY study is consistent with previous observations in metastatic urothelial cancer and other tumor types.
Among all evaluable treated metastatic urothelial cancer patients ( n=113 ), the most common ( 25% or more ) adverse reactions were diarrhea, fatigue, neutropenia, nausea, alopecia, anemia, decreased appetite, constipation, vomiting, and abdominal pain.
Adverse reactions leading to treatment discontinuation occurred in 10% of those receiving Trodelvy, with 4% discontinuing treatment due to neutropenia.
Sacituzumab govitecan-hziy is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the Trop-2 receptor, a protein frequently expressed in multiple types of epithelial tumors, including metastatic triple-negative breast cancer ( TNBC ) and metastatic urothelial cancer, where high expression is associated with poor survival and relapse.
TROPHY-U01 is an ongoing, international, multi-center, open-label, multi-cohort, single-arm study evaluating Trodelvy monotherapy or combination therapy in patients with metastatic urothelial cancer after progression on a Platinum-based regimen and anti-PD-1 / PD-L1-based immunotherapy.
In Cohorts 1 and 2, patients received Trodelvy 10 mg/kg administered intravenously on days 1 and 8 of a 21-day cycle to be continued until disease progression or loss of clinical benefit.
Trodelvy is approved under accelerated approval based on the objective response rate ( ORR ) and duration of response ( DoR ) established in Cohort 1.
Cohorts 2, 3, 4 and 5 of the study are ongoing.
Cohort 2 is assessing the safety and efficacy of Trodelvy monotherapy in Platinum-ineligible patients after progression on anti-PD-1 / PD-L1-based immunotherapy.
Cohort 3 is assessing the safety and efficacy of Trodelvy on days 1 and 8 of a 21-day cycle followed by pembrolizumab at the standard approved dose ( 200 mg ) only on day 1 of a 21-day cycle in patients with metastatic urothelial cancer who have progressed after prior Platinum therapy.
Cohorts 4 and 5 are assessing the safety and efficacy of Trodelvy combination therapy in patients with treatment naive metastatic urothelial cancer, with those in Cohort 4 receiving Cisplatin and those in Cohort 5 receiving Cisplatin and Avelumab, respectively, in addition to Trodelvy.
The primary endpoint is objective response rate based on RECIST 1.1 criteria evaluated by independent central review in all five cohorts.
In Cohorts 1 and 2, secondary endpoints are duration of response and progression-free survival ( PFS ) based on central review and overall survival ( OS ).
Secondary endpoints in Cohorts 3, 4 and 5 include duration of response, clinical benefit rate ( CBR ) and progression-free survival based on central review by RECIST 1.1 criteria; duration of response, clinical benefit rate and progression-free survival based on investigator review by RECIST 1.1 and iRECIST criteria, overall survival and safety and tolerability of Trodelvy in combination with Pembrolizumab, Cisplatin, or Cisplatin and Avelumab, depending on the Cohort.
Urothelial cancer is the most common type of bladder cancer and occurs when the urothelial cells that line the inside of the bladder and other parts of the urinary tract grow unusually or uncontrollably.
An estimated 83,000 Americans will be diagnosed with bladder cancer in 2021, and almost 90% of those diagnoses will be urothelial cancer.
The relative five-year survival rate for patients with metastatic urothelial cancer is 5.5%. ( Xagena )
Source: Gilead, 2021