Abstract 258P
Background
SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to SN-38 via a unique hydrolyzable linker. In the ASCENT study, SG significantly prolonged survival vs chemotherapy of physician’s choice (TPC) in the second line or greater mTNBC setting (median progression-free survival [PFS], 5.6 vs 1.7 mo; median overall survival [OS], 12.1 vs 6.7 mo). Changes in hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status can occur during the temporal course of metastatic disease. While ASCENT required pts to have TNBC on their most recent biopsy at study entry, about one-third did not have TNBC at initial Dx. A subgroup analysis assessed outcomes with SG in these pts.
Methods
Pts with mTNBC refractory to or relapsing after ≥2 prior chemotherapies (≥1 in the metastatic setting) were randomized 1:1 to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by central review in BMNeg pts.
Results
In total 146 pts did not have TNBC at initial Dx, with 70/235 BMNeg pts (30%) who received SG, and 76/233 BMNeg pts (33%) who received TPC. Pts without TNBC at initial Dx had a median age of 55 y (range, 27-80), and 63% had ECOG PS 1. For these pts, SG significantly improved median PFS vs TPC (4.6 vs 2.3 mo; HR, 0.48; P=0.0004), median OS (12.4 vs 6.7 mo; HR, 0.44; P<0.0001), and objective response rate (31% vs 4%). Key treatment-related grade ≥3 adverse events (SG vs TPC) were neutropenia (59% vs 40%), anemia (8% vs 7%), and diarrhea (7% vs 0%). No treatment-related deaths with SG were reported. Efficacy outcomes for pts with TNBC at initial Dx similarly were improved with SG vs TPC; the safety profile was comparable.
Conclusions
The subgroup of pts without TNBC at initial Dx had a significant survival benefit with SG vs TPC, with a manageable safety profile. Outcomes were similar to those of the ASCENT trial’s overall population. Studies are ongoing to further evaluate SG in TNBC (eg, NeoSTAR, NCT04230109; SASCIA, NCT04595565; etc) and HR+/HER2-negative disease (TROPiCS-02, NCT03901339).
Clinical trial identification
NCT02574455.
Editorial acknowledgement
Legal entity responsible for the study
Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
J. O'Shaughnessy: Financial Interests, Personal, Other, Consulting fees: AbbVie Inc.; Agendia Amgen Biotechnology; Aptitude Health; AstraZeneca; Bristol Myers Squibb; Celgene Corporation; Eisai; G1 Therapeutics; Genentech; Immunomedics; Ipsen Biopharmaceuticals; Lilly; Merck; Myriad; Novartis; Ondonate Therapeutics; Pfizer; P. A. Brufsky: Financial Interests, Personal, Other, Consulting fees: Immunomedics (Gilead), Novartis, Genentech, Roche, Eisai, Merck, Athenex . H.S. Rugo: Non-Financial Interests, Institutional, Research Grant, Funding for Sponsored studies to UCSF: Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi, Seattle Genetics, Eisai, Macrogenics, Sermonix, Immunomedics, AstraZeneca; Financial Interests, Personal, Other, Travel Support for Educational Meeting: Daiichi, Mylan, Pfizer, Merck, Novartis, AstraZeneca, Macrogenics; Financial Interests, Personal, Other, Honoraria: Mylan, Puma, Samsung. S.M. Tolaney: Financial Interests, Institutional, Research Grant, PI of studies(all funding to institute): Immunomedics/Gilead, AstraZeneca, Eli Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Exelixis, Bristol Myers Squibb, Eisai, Nanostring, Cyclacel, Sanofi, Odonate; Financial Interests, Personal, Other, Honorarium for consultant/advisory board: Immunomedics/Gilead, AstraZeneca, Eli Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Eisai, Nanostring, Odonate; Financial Interests, Personal, Other, travel expense reimbursement for ad board: Nektar; Financial Interests, Personal, Other, Honorarium for advisory board: Bristol Myers Squibb, Puma, Sanofi, Celldex, Silverback Therapeutics, G1 Therapeutics, OncoPep, Kyowa Kirin Pharmaceuticals, Daiichi Sankyo, Samsung Bioepsis Inc., Certara, Mersana Therapeutics; Financial Interests, Personal, Other, Honorarium for consulting: Seattle Genetics, AbbVie, Athenex, CytomX; Financial Interests, Personal, Other, PI of studies(all funding to institute); Honorarium for consultant/advisory board --outside this study: Immunomedics/Gilead. S. Diab: Financial Interests, Personal, Other, Speaker and advisory board: Immunomedics; Financial Interests, Personal, Other, Personal Fees: Pfizer, AstraZeneca, Genentech, Novartis, Puma Biotechnology, Amgen, Lilly, AbbVie, Eisai, Daiichi Sankyo; Non-Financial Interests, Personal, Other, Non-Financial Support: Pfizer, AstraZeneca, Genentech, Novartis, Puma Biotechnology, Amgen, Lilly, AbbVie, Eisai, Seattle Genetics; Other, Personal and Institutional, Other: Clovis Oncology. K. Punie: Financial Interests, Institutional, Other, Consulting fees: Roularta, Novartis, Roche, Medscape, Vifor Pharma, Pfizer, Pierre Fabre; Financial Interests, Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Lilly, McCann Health, Mundi Pharma, MSD, Novartis, Pfizer, Roche; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: AstraZeneca, Novartis, PharmaMar, Roche, Pfizer; Financial Interests, Institutional, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca, Novartis, Lilly, Roche, Pierre Fabre, Vifor Pharma; Non-Financial Interests, Personal, Other, Committee member of ESMO Young Oncologists Committee: ESMO; Financial Interests, Personal, Member of the Board of Directors, Board member of Belgian Society of Medical Oncology: BSMO; Financial Interests, Institutional, Funding, Research funding to institution: Sanofi. S. Sardesai: Financial Interests, Personal, Other, Consulting fees- Payments to self: Immunomedics, Novartis, Bio Theranostics. E. Hamilton: Financial Interests, Institutional, Funding, research funding (payable to institution only, no personal funds): OncoMed, Genentech/Roche, Zymeworks, Rgenix, ArQule, Clovis, Silverback Therapeutics, Millenium, Acerta Pharma, Sermonix Pharmaceuticals, Torque, Black Diamond, Karyopharm, Infinity Pharmaceuticals, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomed; Financial Interests, Institutional, Other, consulting/advisory role payments( to institution only, no personal funds accepted): Genentech/Roche, Boehringer Ingelheim, Novartis, Dantari, Lilly, Merck, Puma Biotechnology, Silverback Therapeutics, CytomX, Pfizer, Mersana, Black Diamond, H3 Biomedicine, Daiichi Sankyo, AstraZeneca, Arvinas, Deciphera Pharmaceuticals, Eisai, Seagen. D. Loirat: Financial Interests, Personal, Other, Consulting fees: MSD, Novartis, AstraZeneca, Roche, Immunomedics, Pfizer; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen, MSD, Lilly, Novartis, BMS, Roche; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Roche, MSD, AstraZeneca, Novartis; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: MSD. T.A. Traina: Financial Interests, Personal, Other, Consulting or Advisory Role: Genentech/Roche, Pfizer, AstraZeneca, Merck, Puma Biotechnology, Advaxis, Celgene, Innocrin Pharma, Genomic Health, Bristol Myers Squibb, Athenex, Aduro Biotech, Halozyme, Daiichi Sankyo, Ionis Pharmaceuticals, Seattle Genetics, Eisai, Immunomedics; Financial Interests, Institutional, Research Grant, Research Funding: Eisai, Pfizer, Novartis, Innocrin Pharma, AstraZeneca, Astellas Pharma, Immunomedics, Genentech/Roche, Daiichi Sankyo, Carrick Pharm. R. Leon-Ferre: Non-Financial Interests, Personal, Other, Travel support to investigator's meeting: Immunomedics; Other, Personal, Other, Advisory board participation, honoraria to institution for research activities: AstraZeneca. S.A. Hurvitz: Non-Financial Interests, Institutional, Other, Contracted Research: Ambrx, Amgen, AstraZeneca, Arvinas, Bayer, Daiichi Sankyo, Genentech/Roche, Gilead, GSK, Immunomedics, Lilly, Macrogenics, NovarUs, Pfizer, OBI Pharma, Pieris, PUMA, Radius, Sanofi, SeaFle GeneUcs, Dignitana, Zymeworks, Phoenix Molecular Designs, Ltd.; Financial Interests, Personal, Stocks/Shares, Stock Options: NK Max. K. Kalinsky: Financial Interests, Institutional, Research Grant, Grants or contracts from entity: Inctye, Novartis, Genentech, Lilly, Pfizer, Calithera, immunomedics, Acetylon, Seattle Genetics, Amgen, Zeno, Cytomx; Financial Interests, Personal, Other, Consulting fees: Lilly, Pfizer, Novartis, Eisai, AstraZeneca, Genentech, Immumomedics, Merck, Seattle Genetics, Cyclacel, Oncosec; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Lilly; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Lilly, AstraZeneca, Pfizer; Financial Interests, Personal, Other, Steering Committee: Immunomedics, AstraZeneca, Genentech; Other, Personal, Other, Spouse (employee): Grail, Array, Pfizer. A. Bardia: Financial Interests, Institutional, Research Grant, Research Grant to Institution: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics; Financial Interests, Personal, Other, Advisory Board/Consulting: Biothernostics Inc., Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Taiho, Sanofi, Daiichi Pharma/AstraZeneca, Puma, Phillips, Eli Lilly, Foundation Medicine; Financial Interests, Personal, Other, Steering Committee: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics; Financial Interests, Personal, Other, Travel support: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Taiho, Sanofi, Phillips. I. Mayer: Financial Interests, Personal, Research Grant, Research support: Pfizer, Genentech; Financial Interests, Personal, Advisory Board, Ad board: Novartis, Pfizer, Genentech, Lilly, Puma, AbbVie, Immunomedics, Macrogenics, Seattle Genetics, AstraZeneca, GSK, Cyclacel, Blueprint. Q. Hong: Financial Interests, Personal, Full or part-time Employment, Employment: Gilead Sciences, Inc.; Financial Interests, Personal, Stocks/Shares, Stock Ownership: Gilead Sciences, Inc. . S. Phan: Financial Interests, Personal, Full or part-time Employment, Employee of sponsor of the study: Immunomedics; Financial Interests, Personal, Stocks/Shares, Received as employee of company: Immunomedics. J. Cortés: Financial Interests, Personal, Advisory Board, Consulting/Advisor:: Roche +, Celgene -, Celestial, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme +, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Kyowa Kirin.; Financial Interests, Personal, Other, Honoraria: Roche +, Novartis +, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Page 2 of 4 Daiichi Sankyo.; Financial Interests, Institutional, Research Grant, Research funding to the Institution: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F. Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; Financial Interests, Personal, Stocks/Shares, Stock, patents and intellectual property: MedSIR; Financial Interests, Personal, Other, Travel, accommodation, expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo. All other authors have declared no conflicts of interest.