Abstract 796TiP
Background
Checkpoint inhibitors (CPI) are standard therapy for pts with mUC following progression on PLT-based chemotherapy with response rates of 13–29% and limited complete responses. SG is a novel antibody-drug conjugate (ADC) comprised of a humanized monoclonal anti–Trop-2 antibody coupled to SN-38 via a unique hydrolyzable linker. Trop-2 is an epithelial cell surface antigen differentially expressed in malignant vs normal tissues, especially in UC. The phase 1/2 IMMU-132-01 trial reported an ORR of 31% with SG alone in pts with mUC, while interim data from the phase 2 TROPHY-U-01 trial cohort 1 (n=35 pts with heavily pretreated mUC who progressed on PLT, CPI) confirmed those results (ORR 29%).SG toxicity was manageable with notable AEs of neutropenia and diarrhea. An ADC with CPI showed high ORR in pts with previously untreated mUC; we hypothesize that SG with CPI may significantly benefit pts with PLT-refractory mUC.
Trial design
TROPHY-U-01 (NCT03547973) is a multi-cohort, open-label, global phase 2 trial. Cohort 3 will enroll up to 61 CPI-naïve pts with progression/recurrence after PLT-based therapy. Key inclusion criteria: ECOG PS 0 or 1, creatinine clearance ≥30 mL/min, adequate organ function. Key exclusion criteria for cohort 3: active autoimmune disease, history of interstitial lung disease. Three SG doses may be tested in combination with Pembro 200 mg in a 10-pt safety cohort lead-in to determine the recommended phase 2 dose (RP2D). A Simon 2-stage design will be conducted after RP2D identification. Stage 1 contains 21 pts (including 10 pts in the safety lead-in treated with RP2D) and up to 41 pts enrolled at the RP2D, if target clinical activity is noted at stage 1. Pts will first receive SG on days 1 and 8 with Pembro 200 mg only on day 1 of a 21-day cycle until unacceptable toxicity or disease progression. Primary objective is ORR by central review using RECIST 1.1. Secondary objectives are safety/tolerability, DOR, CBR, PFS per investigator and central review by RECIST 1.1, and investigator review by iRECIST criteria. Enrollment began in March 2020 and will continue across ∼40 sites in the USA and France.
Clinical trial identification
NCT03547973.
Editorial acknowledgement
Legal entity responsible for the study
Immunomedics, Inc.
Funding
Immunomedics, Inc.
Disclosure
P. Grivas: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Genentech; Honoraria (institution): Bayer; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Merck; Honoraria (institution): Mirati Therapeutics; Honoraria (institution): Oncogenex; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Honoraria (self), Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Biocept; Honoraria (self), Honoraria (institution), Advisory/Consultancy: 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; Honoraria (institution): Bavarian Nordic; Honoraria (institution): Immunomedics; Honoraria (institution): Debiopharm; Honoraria (self), Advisory/Consultancy: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Genzyme; Honoraria (self), Advisory/Consultancy: Exelixis. 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. N. Agarwal: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Argos; Advisory/Consultancy, Research grant/Funding (institution): 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): 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. 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, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy: Bicycle Therapeutics ; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Clovis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Endocyte; 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; Research grant/Funding (institution): Genentech; Honoraria (self), Advisory/Consultancy: Urogen; 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. Q. Hong: Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunomedics. A. Gladden: Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunomedics. C. Kanwal: Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunomedics; Full/Part-time employment: Novartis. T. Goswami: Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunomedics. Y. Loriot: Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Research grant/Funding (institution): Astellas; Honoraria (self), Research grant/Funding (institution): Janssen; Honoraria (self), Research grant/Funding (institution): Seattle Genetics; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Sanofi; Honoraria (self): Ipsen; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Incyte.