ASCO GU 2019: TROPHY-u-01: A Phase II Open-Label Study of Sacituzumab Govitecan (IMMU-132) in Patients with Advanced Urothelial Cancer after Progression on Platinum-Based Chemotherapy and/or Anti-PD-1/PD-L1 Checkpoint Inhibitor Therapy

San Francisco, CA (  Patients with metastatic urothelial carcinoma (mUC) have poor prognosis. Single-agent chemotherapy is the standard initial treatment and is associated with low response rates (6-14%) and poor overall survival (OS) 7 months. Anti-PD-1/PD-L-1 immunotherapy is presently used as second line therapy and is now the standard of care. For patients who progress after platinum chemotherapy and immunotherapy with programmed death ligand 1 (PD-1)/(PD-L1) inhibitors have limited treatment options. 

Sacituzumab govitecan (SG) is a novel antibody-drug conjugate. The antibody is humanized anti-Trop2 and it is attached to the active metabolite of irinotecan, a cytotoxic chemotherapy agent. The combination drug targets Trop-2 which is overexpressed in aggressive epithelial cancers including up to 83% of UC. SG has shown preclinical and clinical activity in many cancers expressing Trop-2.  

TROPHY-u-01 is an international, single-arm, open-label, phase 2 trial evaluating the antitumor activity and safety of SG in 140 patients with advanced UC. Two cohorts of patients were evaluated. Cohort 1 includes patients in third-line therapy after platinum-based chemotherapy and anti-PD-1/anti-PD-L1 immunotherapy. Cohort 2 includes patients in second line therapy, ineligible for cisplatin-based therapy and after anti-PD-1/anti-PD-L1 immunotherapy. CT/MRI scans were obtained at 8-week intervals to assess treatment response. The primary outcome measures were safety and objective response rate (ORR) by RECIST 1.1. Secondary outcome measures included duration of response (DOR), progression free survival (PFS) and overall survival (OS).  

Key inclusion criteria include histologically confirmed UC, ECOG 0 or 1, adequate hematology, chemistry, hepatic function and coagulation values without repeated transfusions, creatinine clearance >= 30 ml/min, 3-month life expectancy. Key exclusion criteria include prior irinotecan therapy, restrictions on prior monoclonal antibody and chemotherapy treatments, active infection, central nervous system metastases, additional malignancy requiring treatment, hepatitis B/C. 

The study start date was 2018 and it is estimated to come to completion in 2020. 

Presented by: Scott Tagawa, MD, MS Associate Professor of Clinical Medicine, Clinical Urology, at Weill Cornell Medicine; New York, NY 

Written by: Selma Masic, MD, Urologic Oncology Fellow (SUO), Fox Chase Cancer Center, Philadelphia, PA. Twitter:@selmasic at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA