Pivotal phase 3 trial launched to confirm promising results in metastatic urothelial carcinoma.
The antibody-drug conjugate (ADC) sacituzumab govitecan-hziy (Trodelvy) induced an overall response rate (ORR) of 27% in heavily pretreated patients with metastatic urothelial carcinoma following the failure of both platinum-based chemotherapy and checkpoint inhibition, according to the final data from cohort 1 of the phase 2 TROPHY-U-01 trial presented during the 2020 ESMO Congress.1
There were 31 responders, including 6 (5%) complete responses (CRs) and 25 (22%) partial responses (PRs). The median response duration with the ADC was 5.9 months.
"The final results from TROPHY-U-01 cohort 1 confirmed the interim findings and the results from the prior phase 1 study, and showed that sacituzumab govitecan is generally well tolerated and has significant anticancer activity in heavily pretreated [patients with] metastatic urothelial cancer who have progressed on both platinum-based chemotherapy and checkpoint inhibitors,” Yohann Loriot, MD, PhD, lead author of the study and a medical oncologist at the Institut de Cancèrologie Gustave Roussy, in Villejuif, France, said in a presentation during the congress.
The open-label, global phase 2 TROPHY-U-01 trial evaluated sacituzumab govitecan in 3 cohorts: patients with metastatic urothelial carcinoma who progressed on platinum-based chemotherapy and checkpoint inhibition (cohort 1); those who were ineligible for platinum-based chemotherapy and progressed following checkpoint inhibition (cohort 2); and those who never received checkpoint inhibitors but had progressed on platinum-based therapy (cohort 3).
The findings shared at ESMO were from cohort 1, which patients received 10 mg/kg of the ADC on days 1 and 8, every 21 days and continued treatment until loss of clinical benefit or intolerable toxicity. The primary end point of this analysis was ORR per central review.
Among the evaluated patients, the median age was 66 years, with 23% of patients 75 years of age or older and 78% male. Moreover, the majority of patients were white, at 74%. Twenty-eight percent of patients had an ECOG performance status of 0, while 72% had a status of 1. Overall, 62% of patients had visceral metastases; 40% had lung metastases, 28% had liver metastases, and 12% had other.
The median number of prior anticancer regimens received was 3. “Therefore, this is a heavily pretreated patient population, and sacituzumab govitecan was the fourth line of therapy,” noted Loriot.
Sixteen (14%) of 113 evaluable patients continued to receive treatment with sacituzumab govitecan at the time of the analysis. The majority of patients who discontinued treatment did so because of disease progression (66%; n = 75). Only 7% (n = 8) of patients discontinued the ADC because of toxicity. Three percent of patients (n = 3) discontinued because of withdrawn consent and 3% (n = 3) died. The median time on treatment was 3.7 months, according to Loriot, and the maximum time on treatment is 16 months thus far. Fifty-percent of patients (n = 56) are in follow-up for survival.
The median time to onset of response was 1.6 months. The ORR, median DOR, and median time to response reported were consistent with investigator assessments.
“There was a reduction in target lesion size in three-quarters of patients,” noted Loriot. Moreover, 27 of 31 responders were alive with 8 of these patients still experiencing a response and receiving the treatment at the time of the data cutoff.
Regarding safety, diarrhea was the most commonly experienced treatment-related adverse effect, occurring in two-thirds of patients (all grade, 65%); this is consistent with what has been reported in prior studies with the ADC. However, most of these effects were grade 1/2, noted Loriot.
Grade 3 diarrhea occurred in 9% of patients, with only 1% experiencing grade 4. Forty-six percent of patients experienced neutropenia, with 22% having a grade 3 effect and 12% reporting a grade 4 effect. “However, neutropenia was manageable with dose reductions and granulocyte colony-stimulating factor; it was reversible,” said Loriot. “Thirty-percent of patients received GCSF either as primary prophylaxis or in response to neutropenia.”
Moreover, 1 treatment-related death was reported, with a patient presenting with sepsis due to febrile neutropenia.
The phase 3 TROPiCs-04 trial (NCT04527991) is being launched to confirm these promising phase 2 results.
“Sacituzumab govitecan received fast track designation [from the FDA] for this indication and may have the potential to change practice in this setting,” Loriot concluded.
1. Loriot Y, Balar AV, Petrylak DP, et al. Final results from TROPHY-U-01 cohort 1: a phase 2 open-label study of sacituzumab govitecan (SG) in patients with metastatic urothelial cancer (mUC) and disease progression after platinum (PLT)-based regimens and checkpoint inhibitors. Presented at: 2020 ESMO Virtual Congress; September 19-21, 2020; Virtual. Abstract LBA24.