Abstract 276TiP
Background
A checkpoint inhibitor combined with chemotherapy is standard of care for patients (pts) with mTNBC whose tumors are PD-L1+. SG is an antibody-drug conjugate (ADC) comprising an anti-Trop–2 antibody coupled to a cytotoxic SN-38 payload, via a hydrolyzable linker. SG showed significant clinical benefit (progression-free survival [PFS]; overall survival [OS]) over TPC chemotherapy in pts with mTNBC who received ≥2 prior therapies, with ≥1 in the metastatic setting (Bardia et al. NEJM. 2021). ASCENT-04 evaluates whether combining SG, a potent ADC, with pembro improves efficacy outcomes of 1L in PD-L1+ mTNBC.
Trial design
ASCENT-04 (EudraCT: 2021-005742-14) is a global, open-label, randomized, phase III study in 1L locally advanced inoperable, or mTNBC in PD-L1+ (combined positive score ≥10) tumors; pts previously treated with/without anti-PD-L1 agent in the (neo)adjuvant setting may be included. TNBC (human epidermal growth factor receptor 2 negative, estrogen/progesterone receptor <1%) and PD-L1 status will be centrally confirmed. Other inclusion criteria are pts ≥6 mo since completion of treatment with curative intent and ECOG performance status 0-1. Pts with prior treatment with topoisomerase inhibitors are excluded. Pts are randomized 1:1 to receive SG (10 mg/kg IV on D1 and 8) plus pembro (200 mg on D1) in 21-d cycles or TPC (gemcitabine and carboplatin, paclitaxel, or nab-paclitaxel) plus pembro until blinded independent central review (BICR)-verified progressive disease/unacceptable toxicity. Pts randomized to the control arm may be eligible to receive SG upon disease progression. Stratification is based on de novo vs recurrent disease within 6-12 mo of treatment vs recurrent disease occurring after >12 mo from completion of treatment in (neo)adjuvant setting, prior exposure to anti-PD-L1, and geographic region. The primary endpoint is PFS assessed by BICR review per RECIST v1.1. Secondary endpoints include OS, objective response rate, quality of life, and safety. ASCENT-04 will enroll ∼440 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
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; Financial Interests, Personal, Invited Speaker, Honorarium payments to self for participation in advisory boards/consulting from all companies listed – 1 time event: Ellipses Pharma, 4D Pharma, OncoSec, Infinity Therapeutics, BeyondSpring Pharma, OncXerna, Reveal Genomics, ARC Therapeutics, 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. E. de Azambuja: Financial Interests, Personal, Invited Speaker, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Pierre Fabre, Zodiacs, Lilly, Novartis, Seattle Genetics, Libbs; Financial Interests, Personal, Sponsor/Funding, Support for attending meetings and/or travel: Roche; Financial Interests, Personal and Institutional, Advisory Role, Participation on a Data Safety Monitoring Board or Advisory Board: Roche, Seatlle Genetics, Lilly; Financial Interests, Personal and Institutional, Advisory Role, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: ESMO Council, ESC Council, Anticancer Funds. L.A. Emens: Financial Interests, Institutional, Funding, No payments: Gilead Sciences, Inc; Financial Interests, Institutional, Funding, All payments to institution: AbbVie, Astrazeneca, Bolt Therapeutics, Bristol Myers Squibb, Compugen, CytomX, Corvus, EMD Serono, Genentech, F Hoffman La Roche, Immune Onc, Merck, Next Cure, Silverback, Takeda, Tempest; Financial Interests, Personal, Advisory Role, All payments to me: Genentech, F Hoffman La Roche, Chugai, GPCR, Gilead, Immune Onc, AbbVie, Shionogi, Mersana; Financial Interests, Personal, Sponsor/Funding, Travel covered by the company, no transfer of funds to me: Genentech/Roche; Financial Interests, Institutional, Member, Chair: DSMB ENCORE-602 Syndax; Financial Interests, Institutional, Member, Co-Chair, Steering Committee: KATE3, Genentech/Roche, IMpassion130, Genentech/Roche; Financial Interests, Institutional, Member, Chair, Steering Committee: KATE2 Genentech/Roche; Financial Interests, Institutional, Member, Member, Steering Committee,: CTMS-2009-002, ASCENT-04; Financial Interests, Institutional, Member, Volunteer position, Vice President and President-elect: Society for Immunotherapy of Cancer; Financial Interests, Personal, Stocks/Shares, Potential for stock options in future: Molecuvax; Financial Interests, Personal and Institutional, Sponsor/Funding, Medical writing support for congress presentations, manuscripts: Genentech/Roche, Corvus. S. Loi: Financial Interests, Institutional, Funding, research funding to institution: Novartis, Bristol Meyers Squibb, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics, AstraZeneca, Roche-Genentech and Seattle Genetics; Financial Interests, Institutional, Advisory Role, acted as consultant (paid to institution): Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, AstraZeneca, Silverback Therapeutics, G1 Therapeutics, PUMA Biotechnologies, Pfizer, Gilead Therapeutics, Seattle Genetics, Daiichi Sankyo, Amunix, Tallac Therapeutics, Eli Lilly and Bristol Meye; Financial Interests, Institutional, Advisory Role, Paid to institution: OncoSec; Financial Interests, Institutional, Advisory Role, acted as consultant (not compensated): Seattle Genetics, Novartis, Bristol Meyers Squibb, Merck, AstraZeneca, Eli Lilly, Pfizer and Roche-Genentech, Gilead Therapeutics. W. Pan: Financial Interests, Personal, Full or part-time Employment, Stock or Stock Options: Merck and Co.; Financial Interests, Personal, Full or part-time Employment, Salary: Merck and Co.. J. Huang: Financial Interests, Personal, Full or part-time Employment: Gilead Science, Inc.. S.W. Sun: Financial Interests, Personal, Full or part-time Employment, All support for the present manuscript (e.g., funding, provision of study materials, medical writing, article processing charges, etc.): Gilead Scientific Publications; Other, Personal, Other, Patents planned, issued or pending: Docket No. P36659-US Serial No. 63/141377, Pathological Response Calculation And Assessment Tool. C. Lai: Financial Interests, Personal, Full or part-time Employment, Stock or Stock Options: Gilead Science, Inc.; Financial Interests, Personal, Sponsor/Funding, Support for attending meetings and/or travel: Roche/Genentech (former Employee); Financial Interests, Personal and Institutional, Funding, Patents planned, issued or pending: Roche/Genentech (former Employee); Financial Interests, 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). P. Schmid: Financial Interests, Institutional, Advisory Role, Grant/Funding to Institution: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation; Financial Interests, Personal, Advisory Role, Consulting fees: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Eisai, Celgene; Financial Interests, Personal, Invited Speaker, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Eisai, Celgene; Financial Interests, Personal, Full or part-time Employment, Employee – Roche (spouse): Spouse.