Abstract 275TiP
Background
SG is a first-in-class antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to a cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG significantly improved outcomes over standard single-agent chemotherapy in patients (pts) with mTNBC who received ≥2 prior therapies (≥1 in the metastatic setting [Bardia et al. 2021]). Chemotherapy is the mainstay treatment option for 1L programmed death-ligand 1 (PD-L1)-negative mTNBC but is associated with poor outcomes. ASCENT-03 evaluates efficacy and safety of SG vs TPC in 1L locally advanced inoperable or mTNBC in pts with PD-L1-negative mTNBC irrespective of prior immune checkpoint inhibitors (ICI) in the early setting, or in PD-L1 positive mTNBC pts who received prior ICI in the early setting.
Trial design
ASCENT-03 (EudraCT: 2021-005743-79) is a global, open-label, randomized, phase III study in 1L locally advanced inoperable or mTNBC. This study includes pts with either PD-L1-negative tumors (combined positive score [CPS]<10) or PD-L1 positive tumors (CPS ≥ 10) who received an anti-PD-(L)1 inhibitor in the curative setting. TNBC (human epidermal growth factor receptor 2 negative, estrogen/progesterone receptor <1%) and PD-L1 status will be centrally confirmed. Other eligibility criteria include measurable disease; ≥6 mo since completion of treatment with curative intent; ECOG performance status 0-1. Pts are randomized 1:1 to receive SG (10 mg/kg IV on D1 and 8) in 21-d cycles or TPC (gemcitabine/carboplatin, paclitaxel, or nab-paclitaxel) until blinded independent central review (BICR)-verified progressive disease/unacceptable toxicity. Pts randomized to TPC may be eligible to cross over and receive SG upon disease progression. Pts are stratified by de novo vs recurrent disease within 6-12 mo of all treatment vs recurrent disease after >12 mo from completion of all treatment in the (neo)adjuvant setting; geographic region. The primary endpoint is progression-free survival by BICR per RECIST v1.1. Secondary endpoints include overall survival, objective response rate, quality of life, and safety. ASCENT-03 will enroll ∼540 patients and is open for recruitment.
Clinical trial identification
EudraCT 2021-005743-79.
Editorial acknowledgement
Legal entity responsible for the study
Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
A. Bardia: Financial Interests, Personal and Institutional, Research Grant, Grants or contracts from any entity: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health/Menarini, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Role, Consulting fees: Pfizer, Novartis, Genentech, Merck, Radius Health/Menarini, Immunomedics/Gilead, Sanofi, Daiichi Pharma/AstraZeneca, Phillips, Eli Lilly, Foundation Medicine. K. Punie: Financial Interests, Personal and Institutional, Research Grant, Research funding. Paid to my institution: MSD, Sanofi; Financial Interests, Personal and Institutional, Invited Speaker, Honoraria for Consultancy/Advisory/Speaker roles, paid to my institution: AstraZeneca, Gilead Sciences, Eli Lilly, MSD, Mundi Pharma, Novartis, Pfizer, Roche, Medscape, Seattle Genetics, Pierre Fabre; Financial Interests, Personal and Institutional, Invited Speaker, Honoraria for Consultancy/Advisory/Speaker roles, paid to my personal company: AstraZeneca, Gilead Sciences, MSD, Novartis, Roche; Financial Interests, Personal, Sponsor/Funding, Travel support (personal): AstraZeneca, Novartis, Pfizer, PharmaMar, Roche; Non-Financial Interests, Personal, Member of the Board of Directors, Board member: Belgian Society for Medical Oncology; Non-Financial Interests, Personal, Advisory Role, Committee Member: ESMO Young Oncologists Committee and Resilience Task Force; Financial Interests, Institutional, Invited Speaker, Honoraria for Consultancy/Advisory/Speaker roles, paid to my institution: EMA; Financial Interests, Personal, Invited Speaker, Honoraria for Consultancy/Advisory/Speaker roles, paid to my personal company: EMA; Financial Interests, Institutional, Advisory Role, Scientific Advice: Belgian Reimbursement Comité RIZIV/INAMI CTG. C.H. Barrios: Non-Financial Interests, Personal and Institutional, Advisory Role, Steering Committee Member GILEAD ASCENT 03: Gilead Science, Inc.; Financial Interests, Personal and Institutional, Research Grant, Grants or contracts: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, AbbVie, Astellas Pharma, BioMarin, Bristol-Myers Squibb, Daiichi Sankyo, Abraxis Biosciences, AB Sc; Financial Interests, Personal, Advisory Role, Consulting fees: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi; Financial Interests, Personal and Institutional, Invited Speaker, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi; Financial Interests, Personal, Sponsor/Funding, Support for attending meetings and/or travel: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi.; Financial Interests, Personal and Institutional, Advisory Role, Participation on a Data Safety Monitoring Board or Advisory Board: Roche; Financial Interests, Personal and Institutional, Sponsor/Funding, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, AbbVie, Astellas Pharma, BioMarin, Bristol-Myers Squibb, Daiichi Sankyo, Abraxis Biosciences, AB Sc. A. Schneeweiss: Financial Interests, Personal and Institutional, Research Grant, Research Grant: Celgene, Roche, AbbVie; Financial Interests, Personal, Sponsor/Funding, Travel Expenses: Celgene, Roche, Pfizer; Financial Interests, Personal, Invited Speaker, Honoraria: Roche, Celgene, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly, Gilead, GSK, Bayer, Amgen, Pierre Fabre, . X. Zhai: Financial Interests, Personal, Full or part-time Employment, Stock or Stock Options: Gilead Science, Inc.. D.H. huynh, N. Vaksman: Financial Interests, Personal, Full or part-time Employment, Stock or Stock Options: Gilead Science, Inc.. C. Lai: Financial Interests, Personal, Full or part-time Employment: Gilead Science, Inc.; Financial Interests, Personal, Sponsor/Funding, Support for attending meetings and/or travel: Roche/Genentech (former Employee); Financial Interests, Personal and Institutional, Other, Patents planned, issued or pending: Roche/Genentech (former Employee); Financial Interests, Personal, Full or part-time Employment, Stock or stock options: Roche/Genentech (former Employee); Financial Interests, Personal and Institutional, Sponsor/Funding, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Roche/Genentech (former Employee); Financial Interests, Personal and Institutional, Other, Other financial or non-financial interests: Roche/Genentech (former Employee). S.M. Tolaney: Financial Interests, Institutional, Funding, Funding to institute for duration of study: Gilead Science, Inc.; Financial Interests, Institutional, Funding, All funding to institute: AstraZeneca, Eli Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Gilead, Exelixis, BMS, Eisai, Nanostring, Cyclacel, Sanofi, Odonate, SeaGen; Financial Interests, Personal, Invited Speaker, Honorarium payments to self for participation in advisory boards/consulting from all companies listed: AstraZeneca, Eli Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Gilead, BMS, Eisai, Nanostring, Sanofi, Odonate, SeaGen, Daiichi Sankyo, Athenex, CytomX, Blueprint Medicines, Zentalis, Zymeworks, Ellipses Pharma, 4D Pharma, OncoSec, Infinity Therapeutics, BeyondSpring Pharma, OncXerna, Reveal Genomics, ARC Therapeutics; Financial Interests, Personal, Invited Speaker, Honorarium payments to self for participation in advisory boards/consulting from all companies listed – 1 time event: Kyowa Kirin Pharma, G1 Therapeutics, Silverback Therapeutics, Certara, Mersana Therapeutics, OncoPep; Financial Interests, Personal, Invited Speaker, To self – lecture/educational series: Chugai, Genentech/Roche, Eisai, Gilead, AstraZeneca, BMS.