LBA24 - TROPHY-U-01 cohort 1 final results: A phase II study of sacituzumab govitecan (SG) in metastatic urothelial cancer (mUC) that has progressed after platinum (PLT) and checkpoint inhibitors (CPI)

Background

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.

Methods

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%.

Results

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).

Conclusions

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.

Clinical trial identification

NCT03547973.

Editorial acknowledgement

Legal entity responsible for the study

Immunomedics, Inc.

Funding

Immunomedics, Inc.

Disclosure

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.