Evaluation of clinical benefit of sacituzumab govitecan (SG) following enfortumab vedotin (EV) in advanced urothelial cancer (UC): Real-world experience.

Abstract

523 Background: In the TROPHY study, 8.8% of the 113 patients (pts) were enrolled post EV treatment, with ORR to SG of 30% in that small subset. Response to SG post EV in real world populations has not been previously reported. SG has accelerated FDA approval for treatment refractory UC, with ORR of 27% in the TROPHY-U-01 trial. SG was developed contemporaneously to EV, which like SG, is also an antibody-drug conjugate (ADC), composed of an alternate antibody linker and chemotherapy payload. The EV ORR is 40-52% in single agent studies, and outcomes following SG to EV have not been reported. Optimal therapy sequence for advanced UC, concerns for cross resistance between ADCs and other targeted therapies, and biomarker selection for agents is underexplored. We describe clinical outcomes in pts with advanced UC treated with SG following EV. Methods: In this retrospective study of pts with UC treated with SG after progression on EV at the Johns Hopkins Greenberg Bladder Cancer Institute between November 2020 and October 2022, 17 pts were identified. Fourteen received SG in the next line following EV, 3 had other interval therapies between EV and SG. Response was determined by physician assessed RECIST criteria. All pts were response evaluable for prior EV. Three pts died shortly after C1 SG without imaging and were not response evaluable. Results: In our cohort 8 (47%) pts were female, 3 (17.6%) were African-American and 14 (82.4%) were Caucasian. Mean age was 68.3 years. Primary location was bladder for 9 (52.9%) pts and UTUC for 7 (41.2%). One (5.9%) patient had disease in both primary sites. Two (11.8%) pts had lymph node only disease, 8 (47.1%) had metastatic disease in the lungs, 6 (35.3%) in the liver and 1(5.9%) in bone. Mean number of EV cycles was 5.9 (1-12) and PFS was 5.9 months. Best EV response was CR in 1 (5.9%), PR in 10 (58.8%), SD in 2 (11.8%) and PD in 4 (23.5%) pts. SG was dose reduced in C1 with prophylactic growth factor support in 13/17 pts in this heavily pretreated population. Mean number of SG cycles was 3.8 (1.5-6). Best SG response for the 14 response evaluable pts was PR for 3 (21.4%) pts and SD for 3 (21.4%), for a clinical benefit (CR+PR+SD) rate of 42.8%. Eight pts had best response of PD (57.1%). SG discontinuation was for PD in 8 pts (57.1%) and 4 (28.6%) due to functional decline or toxicity. One patient had PD to SG in C2 but received 3 additional cycles due to therapeutic benefit. Three (21.4%) pts continue SG, after 6 cycles with PR and after 5 and 4 cycles with SD. For 14 response evaluable pts, the PFS on SG was 2.4 months. Conclusions: In this retrospective analysis, pts with advanced UC and PD following EV had meaningful clinical benefit rate to SG of 42.8% despite dose reduction in this small late line cohort. Defining optimal sequence of ADCs and other therapies in UC remains an unmet need. Updated data will be presented.