Dataset Information

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors.

ABSTRACT:

Purpose

Patients with metastatic urothelial carcinoma (mUC) who progress on platinum-based combination chemotherapy (PLT) and checkpoint inhibitors (CPIs) have limited options that offer objective response rates (ORRs) of approximately 10% with a median overall survival (OS) of 7-8 months. Sacituzumab govitecan (SG) is a TROP-2-directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC.

Methods

TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label, phase II, registrational study. Cohort 1 includes patients with locally advanced or unresectable or mUC who had progressed after prior PLT and CPI. Patients received SG 10 mg/kg on days 1 and 8 of 21-day cycles. The primary outcome was centrally reviewed ORR; secondary outcomes were progression-free survival, OS, duration of response, and safety.

Results

Cohort 1 included 113 patients (78% men; median age, 66 years; 66.4% visceral metastases; median of three [range, 1-8] prior therapies). At a median follow-up of 9.1 months, the ORR was 27% (31 of 113; 95% CI, 19.5 to 36.6); 77% had decrease in measurable disease. Median duration of response was 7.2 months (95% CI, 4.7 to 8.6 months), with median progression-free survival and OS of 5.4 months (95% CI, 3.5 to 7.2 months) and 10.9 months (95% CI, 9.0 to 13.8 months), respectively. Key grade ≥ 3 treatment-related adverse events included neutropenia (35%), leukopenia (18%), anemia (14%), diarrhea (10%), and febrile neutropenia (10%), with 6% discontinuing treatment because of treatment-related adverse events.

Conclusion

SG is an active drug with a manageable safety profile with most common toxicities of neutropenia and diarrhea. SG has notable efficacy compared with historical controls in pretreated mUC that has progressed on both prior PLT regimens and CPI. The results from this study supported accelerated approval of SG in this population.

SUBMITTER: Tagawa ST

PROVIDER: S-EPMC8315301 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors.

Tagawa Scott T ST Balar Arjun V AV Petrylak Daniel P DP Kalebasty Arash Rezazadeh AR Loriot Yohann Y Fléchon Aude A Jain Rohit K RK Agarwal Neeraj N Bupathi Manojkumar M Barthelemy Philippe P Beuzeboc Philippe P Palmbos Phillip P Kyriakopoulos Christos E CE Pouessel Damien D Sternberg Cora N CN Hong Quan Q Goswami Trishna T Itri Loretta M LM Grivas Petros P

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20210430 22

<h4>Purpose</h4>Patients with metastatic urothelial carcinoma (mUC) who progress on platinum-based combination chemotherapy (PLT) and checkpoint inhibitors (CPIs) have limited options that offer objective response rates (ORRs) of approximately 10% with a median overall survival (OS) of 7-8 months. Sacituzumab govitecan (SG) is a TROP-2-directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC.<h4>Methods</h4>TROPHY-U-01 (ClinicalTrials.gov identifier: NCT0 ...[more]

PMID: 33929895

Similar Datasets

Project description:BackgroundCabozantinib is a multikinase inhibitor of MET, VEGFR, AXL, and RET, which also has an effect on the tumour immune microenvironment by decreasing regulatory T cells and myeloid-derived suppressor cells. In this study, we examined the activity of cabozantinib in patients with metastatic platinum-refractory urothelial carcinoma.MethodsThis study was an open-label, single-arm, three-cohort phase 2 trial done at the National Cancer Institute (Bethesda, MD, USA). Eligible patients were 18 years or older, had histologically confirmed urothelial carcinoma or rare genitourinary tract histologies, Karnofsky performance scale index of 60% or higher, and documented disease progression after at least one previous line of platinum-based chemotherapy (platinum-refractory). Cohort one included patients with metastatic urothelial carcinoma with measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Two additional cohorts that enrolled in parallel (patients with bone-only urothelial carcinoma metastases and patients with rare histologies of the genitourinary tract) were exploratory. Patients received cabozantinib 60 mg orally once daily in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate by RECIST in cohort one. Response was assessed in all patients who met the eligibility criteria and who received at least 8 weeks of therapy. All patients who received at least one dose of cabozantinib were included in the safety analysis. This completed study is registered with ClinicalTrials.gov, NCT01688999.FindingsBetween Sept 28, 2012, and Oct, 20, 2015, 68 patients were enrolled on the study (49 in cohort one, six in cohort two, and 13 in cohort three). All patients received at least one dose of cabozantinib. The median follow-up was 61·2 months (IQR 53·8-70·0) for the 57 patients evaluable for response. In the 42 evaluable patients in cohort one, there was one complete response and seven partial responses (objective response rate 19%, 95% CI 9-34). The most common grade 3-4 adverse events were fatigue (six [9%] patients), hypertension (five [7%]), proteinuria (four [6%]), and hypophosphataemia (four [6%]). There were no treatment-related deaths.InterpretationCabozantinib has single-agent clinical activity in patients with heavily pretreated, platinum-refractory metastatic urothelial carcinoma with measurable disease and bone metastases and is generally well tolerated. Cabozantinib has innate and adaptive immunomodulatory properties providing a rationale for combining cabozantinib with immunotherapeutic strategies.FundingNational Cancer Institute Intramural Program and the Cancer Therapy Evaluation Program.

Dataset Information

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors.

Purpose

Methods

Results

Conclusion

Publications

TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets