Patients with mUC have limited options after progression on PLT/ CPI. SG is an antibody-drug conjugate composed of a humanized IgG1 kappa anti–Trop-2 monoclonal antibody coupled to SN-38 via a unique hydrolyzable linker. TROPHY-U-01 cohort 1 interim results (n=35) reported a 29% objective response rate (ORR). FDA has granted fast track designation for SG (TRODELVY™) in mUC.
TROPHY-U-01 (NCT03547973) is a multicohort, global, open-label, phase 2 study evaluating SG clinical activity (10 mg/kg, days 1 and 8 of 21-day cycles) in patients with unresectable locally advanced or mUC with measurable disease, ECOG PS 0–1, and creatinine clearance ≥30 mL/min. Cohort 1 includes patients progressing after PLT and CPI, with unlimited prior lines of therapy. Primary objective was ORR evaluated by RECIST v1.1 via central review; secondary objectives were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. This cohort had a Simon two-stage design with 90% power to reject the null hypothesis of ORR ≤12%.
113 patients (78% male; median age 66 y; 72% ECOG PS 1; Bellmunt score 0 [12%],1 [54%], 2 [27%],3 [6%]; 62% with visceral metastases) received a median of 3 prior therapies. Central review confirmed an ORR of 27% (31/113; 95% CI 19–37) with 6 complete responses, 25 partial responses and 25% (95% CI 11.5–43.4) ORR in patients with liver metastases. Median DOR was 5.9 mo (95% CI 4.7–8.6) and clinical benefit rate was 37% (42/113). Median PFS and OS were 5.4 mo (95 %CI 3.5- 6.9) and 10.5 mo (95 %CI 8.2–12.3), respectively. Key grade ≥3 treatment-related adverse events were neutropenia (35%), anemia (14%), febrile neutropenia (10%), and diarrhea (10%). There was no treatment-related grade >2 ocular toxicity, neuropathy or interstitial lung disease. There was 1 treatment-related death (neutropenic sepsis).
SG demonstrated meaningful efficacy with manageable toxicity. These results confirm interim findings, suggest that SG may be a treatment option for mUC, and support a randomized phase III trial.
NCT03547973.
Immunomedics, Inc.
Immunomedics, Inc.
Y. Loriot: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Astrazeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Honoraria (self), Advisory/Consultancy: Ipsen; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Incyte. A.V. Balar: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Genentech; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca/MedImmune; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Nektar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Immunomedics. D.P. Petrylak: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Advanced Accelerator Applications; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Astellas; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self), Advisory/Consultancy: Bicycle Therapeutics; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol Myer Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Clovis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Honoraria (self), Advisory/Consultancy: Exelixis; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy: Pharmacyclics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche Laboratories; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Honoraria (self), Advisory/Consultancy: Urogen; Research grant/Funding (institution): Endocyte; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Innocrin; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Progenics; Research grant/Funding (institution): Sanofi Aventis; Shareholder/Stockholder/Stock options: Bellicum; Shareholder/Stockholder/Stock options: Tyme. S.T. Tagawa: Honoraria (self), Research grant/Funding (institution): Immunomedics. A. Rezazadeh: Shareholder/Stockholder/Stock options: ECOM Medical; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Exelixis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy: BMS; Advisory/Consultancy: EMD Serono; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Astellas Medivation; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Genentech/Roche; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Eisai; Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: EMD Serono; Speaker Bureau/Expert testimony: Merck; Speaker Bureau/Expert testimony: Seattle Genetics/Astellas; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Beyond Spring; Research grant/Funding (institution): BioClin Therapeutics; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Bavarian Nordic; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Immunomedics, Epizy; Travel/Accommodation/Expenses: Prometheus Laboratories. A. Fléchon: Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Astellas. R. Jain: Honoraria (self), Speaker Bureau/Expert testimony: Astellas; Honoraria (self), Speaker Bureau/Expert testimony: Pfizer. N. Agarwal: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Argos; Advisory/Consultancy: EMD Serono; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Medivation; Advisory/Consultancy: Clovis; Advisory/Consultancy: Foundation One, Seattle Genetics; Advisory/Consultancy: Astellas; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Nektar; Research grant/Funding (institution): Active Biotech; Research grant/Funding (institution): Bavarian Nordic; Research grant/Funding (institution): Calithera; Research grant/Funding (institution): Celldex; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck; Research grant/Funding (institution): New Link Genetics; Research grant/Funding (institution): Prometheus; Research grant/Funding (institution): Rexahn; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Tracon. M. Bupathi: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Exelixis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Speaker Bureau/Expert testimony: Astellas. P. Barthélémy: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy: MSD; Advisory/Consultancy: EUSAPharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen-Cilag; Honoraria (self): Astellas; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi. P.L. Palmbos: Research grant/Funding (institution): Immunomedics. D. Pouessel: Honoraria (self), Research grant/Funding (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (self): Sanofi; Honoraria (self): Merck; Honoraria (self): Astellas; Honoraria (self): Janssen; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Incyte; Research grant/Funding (institution), Non-remunerated activity/ies: Janssen; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self): Ipsen; Honoraria (self), Non-remunerated activity/ies: Pfizer. C.N. Sternberg: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: UroToday. Q. Hong: Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunomedics. T. Goswami: Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunomedics. L.M. Itri: Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunomedics; Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: The Medicines Company; Shareholder/Stockholder/Stock options, Immediate Family Member: MSKCC. P. Grivas: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Genentech; Honoraria (self), Research grant/Funding (institution): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): Oncogenex; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Advisory/Consultancy: Biocept; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): ClovisOncology; Honoraria (self), Advisory/Consultancy: EMD Serono; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: Foundation Medicine; Honoraria (self), Advisory/Consultancy: Driver Inc.; Honoraria (self), Advisory/Consultancy: QED Therapeutics; Honoraria (self), Advisory/Consultancy: Heron Therapeutics; Honoraria (self), Advisory/Consultancy: Janssen; Research grant/Funding (institution), Non-remunerated activity/ies: Bavarian Nordic; Research grant/Funding (institution), Non-remunerated activity/ies: Immunomedics; Research grant/Funding (institution), Non-remunerated activity/ies: Debiopharm; Honoraria (self), Advisory/Consultancy: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Genzyme; Honoraria (self), Advisory/Consultancy: Exelixis. All other authors have declared no conflicts of interest.