ASCO GU 2022: TROPHY-U-01 Cohort 3: Sacituzumab Govitecan in Combination with Pembrolizumab in Patients with Metastatic Urothelial Cancer Who Progressed After Platinum-Based Regimens

( The 2022 GU ASCO Annual meeting included a urothelial carcinoma oral abstract session featuring Dr. Petros Grivas and colleagues presenting results of TROPHY-U-01 Cohort 3, sacituzumab govitecan in combination with pembrolizumab in patients with metastatic urothelial cancer who progressed after platinum-based regimens. Outcomes of patients with metastatic urothelial carcinoma are poor with an estimated 5-year survival rate of ~15%. Unfortunately, outcomes remain poor and treatment options are relatively limited for patients with disease progression on platinum-based chemotherapy. Checkpoint inhibitors are standard therapy for patients with metastatic urothelial cancer after platinum-based regimens, with limited long-term disease control. Sacituzumab govitecan is an antibody-drug conjugate composed of an anti-trophoblast cell-surface antigen 2 (Trop-2) antibody coupled to SN-38 (a topoisomerase-I inhibitor) via a proprietary hydrolysable linker. In the TROPHY-U-01 registration phase 2 trial, sacituzumab govitecan monotherapy demonstrated significant activity and manageable safety in patients with metastatic urothelial cancer who progressed after prior platinum-based chemotherapy and checkpoint inhibitors, with a 27% objective response rate (ORR) and median overall survival of 11 months.1

Antibody drug conjugates can induce immunogenic cell death, possibly resulting in additive or synergistic activity when combined with checkpoint inhibitors. Such combination strategy (enfortumab vedotin + pembrolizumab) was assessed in patients with cisplatin-ineligible metastatic urothelial carcinoma in the EV-103 cohort A trial, with preliminary results suggesting favorable safety and efficacy with enfortumab vedotin + pembrolizumab in the first-line setting. At GU ASCO 2022, Dr. Grivas presents the interim efficacy and safety results of combining sacituzumab govitecan with pembrolizumab as second-line therapy in checkpoint inhibitor-naive patients with metastatic urothelial cancer who progressed after platinum-based chemotherapy (cohort 3).

TROPHY-U-01 is a multicohort, open-label, global phase 2 trial. Eligible patients had measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0–1, and creatinine clearance ≥30 mL/min. The recommended phase 2 dose (RP2D) was determined during a 10-patient safety lead-in, and additional patients were enrolled at the RP2D in a Simon 2-stage design. The primary endpoint for TROPHY-U-01 cohort 3 was ORR by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The key secondary endpoints included investigator-assessed ORR, clinical benefit rate [complete response (CR) + partial response (PR) + stable disease], progression-free survival (PFS), and safety. The trial design for TROPHY-U-01 is as follows: 

Petros Grivas-0.jpg 

With >=13 responses observed, the null hypothesis of true ORR <= 20% would be rejected in 1-sided alpha level of 0.05.

At the time of data cutoff, 41 patients received at least a dose of sacituzumab govitecan at the RP2D (10 mg/kg). Of these 41 patients, the median age was 67 years (range: 46–86), 83% were men, 61% were ECOG performance status 1, 76% had ≥1 Bellmunt risk factor, and the median number of prior anticancer regimens was 1 (range: 1–3). At a median follow-up of 5.8 months, the investigator-assessed ORR was 34% (95% CI 20.1–50.6; 1 CR; 13 PR), clinical benefit rate was 61% (95% CI 44.5–75.8), median PFS was 5.5 months (95% CI 1.7-not reached), and median OS was not reached. The median time to response was 2.0 months (95% CI 1.3–2.8) and median duration of response was not reached (95%CI 2.8 – not reached). There were 63% of patients that had tumor shrinkage:


The patient response assessment from the start of treatment to progression is as follows: 


The most common treatment-emergent adverse events were diarrhea (76%), nausea (59%), anemia (56%), neutropenia (44%), and asthenia (41%). Treatment-related grade ≥3 adverse events occurred in 59% of patients. Key grade ≥3 treatment-emergent adverse events of any cause included diarrhea (24%), anemia (20%), febrile neutropenia (10%), fatigue (7%), and asthenia (5%). Two patients discontinued treatment due to treatment-related adverse events and there were no treatment-related deaths. Limitations noted by Dr. Grivas include the small sample size, short follow-up, and lack of randomization.

Dr. Grivas concluded his presentation of the TROPHY-U-01 cohort 3 study with the following take-home messages:

  • Sacituzumab govitecan in combination with pembrolizumab demonstrated encouraging ORR (34%) and clinical benefit rate (61%), with an overall manageable safety profile with no new safety signal in checkpoint inhibitor-naive patients who progressed after prior platinum-based chemotherapy
  • At 5.8 months of median follow-up, the median duration of response and median OS were not reached
  • The data support further evaluation of sacituzumab govitecan plus checkpoint inhibitors in metastatic urothelial cancer
  • Additional follow-up and biomarker evaluation is ongoing
  • Other TROPHY-U-01 cohorts are being assessed including sacituzumab govitecan post checkpoint inhibitors in platinum-ineligible patients with metastatic urothelial carcinoma (cohort 2), sacituzumab govitecan + cisplatin (cohort 4), and sacituzumab govitecan + cisplatin + avelumab (cohort 5) in platinum-naïve patients (both followed by avelumab switch maintenance)
Presented by: Petros Grivas, MD, PhD, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA

Co-Authors: Damien Pouessel, Chandler H. Park, Philippe Barthélémy, Manojkumar Bupathi, Daniel P. Petrylak, Neeraj Agarwal, Aude Flechon, Chethan Ramamurthy, Nancy B. Davis, Alejandro Recio-Boiles, Scott T. Tagawa, Cora N. Sternberg, Astha Bhatia, Cabilia Pichardo, Trishna Goswami, Yohann Loriot

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022 


  1. Tagawa ST, Balar AV, Petrylak DP, et al. Metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors. J Clin Oncol. 2021 Aug 1;39(22):2474-2485.