Abstract 700P
Background
Trop-2, an epithelial cell surface antigen highly expressed in many solid tumors, has been associated with poor outcomes. SG, an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to an SN-38 payload via a proprietary hydrolyzable linker has received accelerated FDA approval in mUC based on data from the TROPHY U-01 study. Data from cohorts 1 and 2 of the study demonstrated an objective response rate [ORR] of 27% and 29%, respectively, in pretreated populations. This pooled (cohorts 1 and 2) analysis evaluated the levels of Trop-2 expression and their association with outcomes.
Methods
Pts with mUC who progressed after or were ineligible for platinum and progressed on prior checkpoint inhibitors received SG (10 mg/kg IV, d 1 and 8, every 21 d) until progression/unacceptable toxicity. Primary endpoint was ORR by central review per RECIST v1.1. Tumor samples were collected at study entry to determine membrane Trop-2 expression using an immunohistochemistry assay. Scoring accounted for the percentage of cells with specific staining intensity (H-score; intensity multiplied by proportion of cells with Trop-2 staining; scale, 0-300).
Results
Ninety-two of the 135 SG-treated pts from cohorts 1 and 2 had Trop-2 H-Score expression data (cohort 1, 85/113 [75%]; Cohort 2, 7/22 [32%]). Those with Trop-2 expression data had an ORR of 32% (29/92). Trop-2 expression was high in the majority of pts (median H-score, 219; range, 0-300). Most pts (66%; n=61) had high H-scores (>200 to 300) whereas 28% (n=26) had medium (≥100 to 200). Only 5% (n=5) had low (0 to <100) H-scores. Clinical outcomes across high, medium, and low groups, respectively, were ORR of 34% (95% CI, 23-48), 27% (95% CI, 12-48), and 20% (95% CI, 1-72), and a median duration of response of 6.7 mo (95% CI, 4.4-8.3), 13.7 mo (95% CI, 2.4-13.7), and 2.5 mo (95% CI, not evaluable). One pt with an H-score of 15 achieved PR.
Conclusions
This exploratory analysis shows that high/medium Trop-2 expression is prevalent in UC and that activity was noted across Trop-2 expression levels. Further evaluation of SG is ongoing (phase II TROPHY U-01 [NCT03547973], cohorts 2-5; phase III TROPiCS-04, [NCT04527991]).
Clinical trial identification
NCT03547973.
Editorial acknowledgement
Legal entity responsible for the study
Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
Y. Loriot: Financial Interests, Institutional, Research Grant: Janssen, Celsius, MSD; Financial Interests, Personal, Speaker’s Bureau: BMS, Pfizer, Merck Kg, MSD, AstraZeneca, Roche, Janssen, Astellas, Seattle Genetics, Immunomedics; Financial Interests, Institutional, Speaker’s Bureau: BMS, Pfizer, Janssen, Merck Kg; Financial Interests, Personal, Officer, Meetings/Travel: BMS, Roche, AstraZeneca, MSD, Pfizer. A.V. Balar: Financial Interests, Institutional, Research Grant: Seagen, Nektar, AstraZeneca, Merck, Genentech, Gilead Sciences, Immunomedics; Financial Interests, Personal, Advisory Board: EpiVax Oncology,Istari Oncology,Seagen, Nektar,AstraZeneca,Pfizer, BMS, Janssen, MerckIncyte, Genetech, Gilead Sciences, Immunomedics; Financial Interests, Personal, Speaker’s Bureau: Nektar,AstraZeneca,Merck, Genentech; Financial Interests, Personal, Other, Equity: EpiVax Oncology. D.P. Petrylak: Financial Interests, Institutional, Research Grant: Ada Cap (Advanced Accelerator Applications), Agensys Inc, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Eisai, Eli Lilly, Endocyte, Genentech, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer; Financial Interests, Personal, Advisory Board, Consulting fees: Ada Cap (Advanced Accelerator Applications), Agensys Inc, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Eisai, Eli Lilly, Endocyte, Genentech, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer; Financial Interests, Personal, Stocks/Shares: Bellicum (sold 7/2020) Tyme (sold 10/2019). A. Rezazadeh: Financial Interests, Personal, Stocks/Shares, Ownership Interests: ECOM Medical; Financial Interests, Personal, Advisory Board, Consulting advisory role: Exelixis, AstraZeneca, Bayer, Pfizer, Novartis, Genentech, BMS, EMD Serono, Immunomedics, Gilead Sciences; Financial Interests, Personal, Speaker’s Bureau: Janssen, Astellas Medivation, Pfizer, Novartis, Sanofi, genentech/Roche, Eisai, AstraZeneca, BMS, Amgen, Exelixis, EMD Serono, Merck, Seattle Genetics, Astellas, Myovant Sciences, Gilead Sciences, AVEO; Financial Interests, Institutional, Research Grant: Genentech, Exelixis, Janssen, AstraZeneca, Bayer, BMS, Eisai, Macrogenics, Astellas Pharma, Beyond Spring, BioClin Therapeutics, Clovis Oncology, Bavarian Nordic, Seattl;e Genetics, Immnomedics, epizy; Financial Interests, Personal, Other, Travel, accommodation, expenses: Genentech, Promethius Laboratories, Astellas Medivation, Janssen, Eisai, Bayer, Pfizer, Novartis, Exelixis, AstraZeneca. P. Grivas: Financial Interests, Personal, Other, Support for this study: Immunomedics, Inc.; Financial Interests, Personal, Research Grant: Merck, Mirati Therapeutics, Pfizer, Clovis Oncology, Bavarian Nordic, Immunomedics, Debiopharm, Bristol-Myers Squibb, QED Therapeutics, GlaxoSmithKline; Financial Interests, Personal, Advisory Board, Consulting fees: AstraZeneca; Bayer; Bristol-Myers Squibb; Clovis Oncology; Dyania Health, Driver; EMD Serono; Exelixis; Foundation Medicine; Genentech/Roche; Genzyme; GlaxoSmithKline; Heron Therapeutics; Immunomedics; Infinity Pharmaceuticals, Janssen; Merck; Mirati Ther; Financial Interests, Personal, Other, Suport for attending meetings/travel: AstraZeneca; Clovis Oncology; Financial Interests, Personal, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Kure IT Cancer Research. A. Fléchon: Financial Interests, Personal, Other, Travel Expenses: MSD, Pfizer, Immu132, Roche, AstraZeneca, Astellas, Janssen. R.K. Jain: Financial Interests, Personal, Speaker’s Bureau: Seattle Genetics; Financial Interests, Personal, Advisory Board: Gilead, Seattle Genetics, EMD Soreno. N. Agarwal: Financial Interests, Research Grant: AstraZeneca, Bavarian Nordic, Bayer, BN Immunotherapeutics, BMS, Calithera, Celldex, Clovis, Eisai, Eli Lilly, EMD Serono, Elelixis, Genetech, Glaxo Smith Kline, Immunomedics, Janssen, Medivation, Merck, Nektar, New Link Genetics, Novartis, Pfizer, Promet; Financial Interests, Advisory Board: Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Janssen, Merck, Nektar, Novartis, Pfizer, Pharmacyclics, Seattle Genetics, Aveo, MEI Pharma. M. Bupathi: Financial Interests, Personal, Advisory Board, Consultant/advisory fees: Astellas, BMS, AstraZeneca, Aveo, FoundationOne, Pfizer, Exelixis, Janssen; Financial Interests, Personal, Speaker’s Bureau: BMS, AstraZeneca, Genentech, Pfizer, SeaGen, Janssen. P. Barthelemy: Financial Interests, Personal, Advisory Board, Consultant/advisory fees: Ipsen, Pfizer, Astellas, Amgen, BMS, AstrZeneca, Merck, MSD, Janssen; Financial Interests, Personal, Speaker’s Bureau: Ipsen, Pfizer, Astellas, Amgen, BMS, AstraZeneca, Merck, MSD, Janssen, Seagen, Novartis; Financial Interests, Personal, Other, Suport for attending meetings or travel: Ipsen, Pfizer, Astellas, Amgen, BMS, Janssen. D. Pouessel: Financial Interests, Personal, Other, No further details provided: AstraZeneca, Sanofi, Pfizer, Merck, Astellas, Janssen, Ipsen, BMS; Financial Interests, Personal, Research Grant: MSD, Roche, Incyte, AstraZeneca, Janssen, BMS; Non-Financial Interests, Personal, Invited Speaker, No further details provided: AstraZeneca, Janssen, Pfizer. C.N. Sternberg: Financial Interests, Personal, Other, Honoraria: Pfizer, MSD, Merck, AstraZeneca, Astellas, Sanofi-Genzyme, Roche-Genentech, Incyte, BMS, Foundation Medicine, Immunomedics now Gilead, NeoTx, Medscape, UroToday, CCO Clinical, NCI; Financial Interests, Personal, Advisory Board, Consultant/advisory fees: IMPACT Pharma, NCI. Y. Pan: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences. J.M. Jürgensmeier: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences; Financial Interests, Personal, Stocks/Shares: Gilead Sciences. T. Goswami: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences. S.T. Tagawa: Financial Interests, Institutional, Research Grant, Institutional Research Support (Weill Cornell): Immunomedics, Inc., Sanofi, Medivation, Astellas, Janssen, AMgen, Progenics, Dendreon, Lilly, Genentech, Newlink, BMS, Inovio, AstraZeneca, Aveo, Rexahn, Atlab, Boehringer Ingelheim, Millenium, Bayer, Merck, AbbVie, Karopharm, Endocyte, Clovia, Seattle G; Financial Interests, Personal, Other, Honoraria since 2007: Immunomedics, Inc., Sanofi, Medivation, Astellas, Janssen, Amgen, Dendreon, Genentech, Bayer, AbbVie, Endocyte, Clovia, Seattle Genetics, AAA/Novartis, POINT Biopharma, Eisai, Karyopharm, Tolmar, QED, Pfizer, Clarity, Genomic Health, Blue Earth Diagnostics. All other authors have declared no conflicts of interest.