1900 - Initial Results From TROPHY-U-01: A Phase 2 Open-Label Study of Sacituzumab Govitecan in Patients (Pts) With Metastatic Urothelial Cancer (mUC) After Failure of Platinum-Based Regimens (PLT) or Immunotherapy

Background

Pts with mUC have limited options after progression on PLT/checkpoint inhibitors (CPI). Sacituzumab govitecan (SG) is an antibody-drug conjugate comprising a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 via a unique hydrolysable linker. In a prior phase I/II study, SG showed significant clinical activity and manageable toxicity in 45 heavily pretreated mUC pts (ORR: 31% overall).

Methods

TROPHY-U-01 (NCT03547973) is a global, open-label, phase II trial evaluating the antitumor activity of SG (10 mg/kg, days 1, 8 of 21-day cycles) in pts with mUC with measurable disease, ECOG performance status 0 or 1, and creatinine clearance ≥30 mL/min. This pre-planned interim analysis based on investigator assessment per RECIST v1.1 reports data from Cohort 1 (pts who progressed after both PLT and CPI). Cohort 1 (N = 35) had a Simon two-stage design with a prespecified futility stopping rule of 11% ORR.

Results

35 pts with ≥1 post -baseline response assessment (80% male; median age 64 y [range 43-90], 77% ≥1 Bellmunt risk factors) received a median of 3 (range 2-7) prior therapies. At a median follow-up of 4.1 mon, ORR was 29% (10/35) with 2 confirmed CR, 5 confirmed PR, and 3 unconfirmed PR (all 3 ongoing and awaiting radiographic confirmation); 74% (26/35) of pts had target lesion reduction. ORR was 25% [2/8] in pts with liver involvement. The safety profile was consistent with prior reports. Key Grade ≥3 treatment-related AEs were neutropenia (23%), anemia (17%), febrile neutropenia (11%), diarrhea (11%). No events of interstitial lung disease, ocular toxicities, or grade >2 neuropathy were reported. There were no treatment-related deaths.

Conclusions

Interim Cohort 1 results from TROPHY-U-01 surpassed the pre-specified futility stopping rule and enrollment continues. Findings confirm prior phase I/II study results of SG as well-tolerated with significant antitumor activity in mUC pts after both prior PLT and CPI. In this population that continues to have a high unmet medical need despite recent progress, the ORR of 29% compares favorably with single-agent chemotherapy (ORR of 9%–14%).

Clinical trial identification

NCT03547973 (release date: June 6, 2018).

Editorial acknowledgement

Editorial support was provided by Cindy Gobbel, PhD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Immunomedics, Inc.

Legal entity responsible for the study

Immunomedics Inc.

Funding

Immunomedics Inc.

Disclosure

S.T. Tagawa: Advisory / Consultancy, Research grant / Funding (institution): Medivation; Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): Dendreon; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Endocyte; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Immunomedics; Advisory / Consultancy, Research grant / Funding (institution): Karyopharm Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy: Tolmar; Advisory / Consultancy: QED Therapeutics; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Progenics; Research grant / Funding (institution): Millennium; Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Rexahn Pharmaceuticals; Research grant / Funding (institution): Newlink Genetics; Research grant / Funding (institution): Inovio Pharmaceuticals; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): AVEO; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Stemcentrx; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Clovis Oncology. A. Balar: Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics. D.P. Petrylak: Advisory / Consultancy, Research grant / Funding (institution): Advanced Accelerator Applications; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Clovis; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Incyte; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Pharmacyclics; Advisory / Consultancy, Research grant / Funding (institution): Roche Laboratories; Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Innocrin; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Endocyte; Advisory / Consultancy: Urogen; Research grant / Funding (institution): Progenics; Research grant / Funding (institution): Sanofi Aventis; Research grant / Funding (institution): Merck; Shareholder / Stockholder / Stock options: Bellicum ; Shareholder / Stockholder / Stock options: Tyme. P. Grivas: Research grant / Funding (institution), to University of Washington for clinical trial conduction: Immunomedics; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Non product speaker’s program, fees to CCF for trial and consulting (unrelated to this study): Genentech; Advisory / Consultancy, consulting (unrelated to this study): Dendreon; Advisory / Consultancy, Research grant / Funding (institution), fees to clev. clinic foundation for clin trial conduction and consulting (unrelated): Bayer; Advisory / Consultancy, Research grant / Funding (institution), clinical trial conduction (unrelated to this study), consulting unrelated to this study: Merck & Co.; Research grant / Funding (institution), clinical trial conduction (unrelated to this study): Mirati; Research grant / Funding (institution), fees to clev. clinic foundation for clin trial conduction (unrelated to study) : Oncogenex; Advisory / Consultancy, Research grant / Funding (institution), consulting, fees to CCF and University of Washington for trial conduction (unrelated to study) : Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, consulting and non product related speaker program (unrelated to this study): Bristol-Myers Squibb; Advisory / Consultancy, consulting unrelated to this study: Exelixis; Advisory / Consultancy, Research grant / Funding (institution), consulting and fees to CCF for trial conduction (unrelated to this study): AstraZeneca; Advisory / Consultancy, consulting (unrelated to this study): Biocept; Advisory / Consultancy, Research grant / Funding (institution), consulting (unrelated to this study), to University of Washington for unrelated clinical trial: Clovis Oncology; Advisory / Consultancy, consulting (unrelated to this study): EMD Serono; Advisory / Consultancy, consulting (unrelated to this study): Seattle Genetics; Advisory / Consultancy, consulting (unrelated to this study): Foundation Medicine; Advisory / Consultancy, consulting (unrelated to this study): Driver Inc.; Advisory / Consultancy, consulting (unrelated to this study): QED Therapeutics; Advisory / Consultancy, consulting (unrelated to this study): Heron Therapeutics; Advisory / Consultancy, consulting (unrelated to this study): Janssen; Research grant / Funding (institution), to University of Washington for clinical trial conduction (unrelated to this study): Bavarian Nordic. N. Agarwal: Advisory / Consultancy, Scientific advisory board: Astellas; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: AstraZeneca; Advisory / Consultancy, Scientific advisory board: Argos; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Bayer; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Clovis; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Eisai; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Exelixis; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: EMD Serono; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Eli Lilly; Advisory / Consultancy, Scientific advisory board: Foundation One; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Genentech; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Janssen; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Merck; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Medivation; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Nektar; Advisory / Consultancy, Research grant / Funding (institution), Scientific advisory board: Pfizer; Advisory / Consultancy, Scientific advisory board: Pharmacyclics; 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): 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. C.N. Sternberg: Advisory / Consultancy: Merck; Advisory / Consultancy: Clovis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Incyte; Advisory / Consultancy: AstraZeneca; Research grant / Funding (institution): Janssen. Q. Hong: Shareholder / Stockholder / Stock options, Full / Part-time employment: Immunomedics; Shareholder / Stockholder / Stock options: Bristol-Myers Squibb; Shareholder / Stockholder / Stock options, Full / Part-time employment, Spouse / Financial dependant, Spouse employment and stock ownership: Merck & Co.; Travel / Accommodation / Expenses: Advaxis Inc. A. Gladden: Full / Part-time employment, Clinical Operations Study Lead: Immunomedics. C. Kanwal: Full / Part-time employment: Immunomedics, Inc.. P. Siemon-Hryczyk: Shareholder / Stockholder / Stock options, Full / Part-time employment: Immunomedics. T. Goswami: Full / Part-time employment: Immunomedics. L.M. Itri: Advisory / Consultancy: Immunomedics, Inc. . Y. Loriot: Non-remunerated activity/ies, Investigator: Immunomedics; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies, Fees for consulting, travel paid, investigator: AstraZeneca; Advisory / Consultancy, Non-remunerated activity/ies, Fees for consulting, investigator: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies, Fees for consulting and travel paid, investigator: Seattle Genetics; Speaker Bureau / Expert testimony, Non-remunerated activity/ies, Lectures, investigator: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies, Fees for consulting, lectures, travel, investigator: Janssen; Advisory / Consultancy, Non-remunerated activity/ies, Fees for consulting, investigator: Incyte; Advisory / Consultancy, Non-remunerated activity/ies, Fees for consulting, lectures and travel paid, investigator: Roche; Speaker Bureau / Expert testimony, Non-remunerated activity/ies, Fees for lecture, investigator: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies, Fees for consulting, lectures and travel paid, investigator: MSD; Advisory / Consultancy, Non-remunerated activity/ies, Fees for consulting, investigator: Nektar; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Non-remunerated activity/ies, Fees for consulting, lectures and travel paid, investigator: Bristol-Myers Squibb.