LBA17 - ASCENT: A randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC)

Background

In pts with pretreated mTNBC, standard of care (SOC) chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (mPFS). SG (TRODELVY™) is a first-in-class antibody-drug conjugate (ADC) composed of an anti–Trop-2 antibody coupled to the active metabolite of irinotecan, SN-38, via a unique hydrolyzable linker that allows for SN-38 release intracellularly and in the tumor microenvironment (bystander effect). In a phase I/II IMMU-132-01 study, SG demonstrated 33% ORR and an mPFS of 5.5 months (mo) in pts with mTNBC with manageable safety, leading to accelerated US FDA approval of SG. The randomized phase III ASCENT study was initiated to confirm those results.

Methods

In the ASCENT study (NCT02574455), pts with mTNBC who had relapsed/refractory disease after ≥2 prior chemotherapies in the advanced/metastatic setting (prior taxane required) were randomized 1:1 to receive SG (10 mg/kg IV on d 1, 8 every 21 d) or single-agent TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. The primary endpoint was PFS measured by central review per RECIST v1.1 in the brain metastases-negative population (BMneg). Key secondary endpoints were overall survival (OS), ORR RECIST v1.1, and safety.

Results

Of 529 pts enrolled, 468 were BMneg (median age, 54 y; median prior lines, 4). SG (n=235) compared with TPC (n=233) significantly improved mPFS (5.6 vs 1.7 mo; HR, 0.41; P<0.0001) and median OS (12.1 vs 6.7 mo; HR, 0.48; P<0.0001). ORR was 35% for SG vs 5% for TPC (P<0.0001). In the safety population (pts who received ≥1 dose of study drug; n=482), key treatment-related grade ≥3 adverse events with SG (n=258) vs TPC (n=224) were neutropenia (51% vs 33%), diarrhea (10.5% vs <1%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%). No grade >3 neuropathy or interstitial lung disease, and no treatment-related deaths were reported with SG.

Conclusions

ASCENT is the first phase III study of an ADC with significant PFS and OS improvement over SOC chemotherapy in pretreated mTNBC, confirming the clinical activity and safety profile of SG monotherapy.

Clinical trial identification

NCT02574455.

Editorial acknowledgement

Editorial and writing support was provided by Shala Thomas, PhD, of Team 9 Science, funded by Immunomedics, Inc.

Legal entity responsible for the study

Immunomedics Inc.

Funding

Immunomedics Inc.

Disclosure

A. Bardia: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Radius Health; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Immunomedics; Research grant/Funding (institution): Mersana; Research grant/Funding (institution): Innocin; Advisory/Consultancy: Biothernostics, Inc.; Advisory/Consultancy, Travel/Accommodation/Expenses: Spectrum Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Taiho; Advisory/Consultancy: Daiichi Pharma/AstraZeneca; Advisory/Consultancy: Puma; Advisory/Consultancy, Travel/Accommodation/Expenses: Philipps; Advisory/Consultancy: Eli Lilly. S.M. Tolaney: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Nektar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Research grant/Funding (institution): Exelixis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: NanoString; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Puma; Research grant/Funding (institution): Cyclacel; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Celldex; Honoraria (self), Advisory/Consultancy: Paxman; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Odonate; Honoraria (self): Seattle Genetics; Honoraria (self), Advisory/Consultancy: Silverback Therapeutics; Honoraria (self), Advisory/Consultancy: G1 Therapeutics; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Anthenex. D. Loirat: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self): Amgen; Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Novartis. K. Punie: Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: Mundi Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Hoffmann-La Roche; Honoraria (self): European centre for clinical research training; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Vifor Pharma; Travel/Accommodation/Expenses: PharmaMar; Research grant/Funding (self): Sanofi. M. Oliveira: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Puma Biotechnology; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Philips Healthcare; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Celldex; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Piqur; Research grant/Funding (institution): Zenith Epigenetics; Travel/Accommodation/Expenses: Grunenthal Group; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: GP Pharm; Travel/Accommodation/Expenses: Eisai. H.S. Rugo: Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational meeting: Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational meeting: Novartis; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational meeting: Macrogenics; Research grant/Funding (institution): OBI Pharma; Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational meeting: Merck; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational meeting: Daiichi; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Odonate; Travel/Accommodation/Expenses, Educational meeting: Mylan; Travel/Accommodation/Expenses, Educational meeting: AstraZeneca; Advisory/Consultancy, One-time: Samsung; Advisory/Consultancy, One-time: Puma. A. Brufsky: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Agendia; Advisory/Consultancy: Celgene; Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Bayer; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Biotheranostics; Advisory/Consultancy: NanoString Technologies; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Puma Biotechnology; Advisory/Consultancy: Bioarray Therapeutics; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Myriad Pharmaceuticals; Advisory/Consultancy: Eisai; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Daiichi Sankyo/Lilly. K. Kalinsky: Advisory/Consultancy, Research grant/Funding (institution): Immunomedics; Advisory/Consultancy, Research grant/Funding (institution), Spouse/Financial dependant: Novartis; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution), Spouse/Financial dependant: Pfizer; Research grant/Funding (institution): Calithera Biosciences; Research grant/Funding (institution): Acetylon; Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Zentalis Pharmaceuticals; Research grant/Funding (institution): CytomX Therapeutics; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Spouse/Financial dependant: Array Biopharma. J. Cortés: Shareholder/Stockholder/Stock options: MedSIR; Honoraria (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self): Roche; Honoraria (self): Samsung; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Cellestia Biotech; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Biothera; Advisory/Consultancy: Merus; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Erytech Pharma; Advisory/Consultancy: Polyphor; Advisory/Consultancy: Athenex; Advisory/Consultancy: Servier; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Leuko; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Bioasis; Advisory/Consultancy: Boehringer Ingelheim; Research grant/Funding (institution): ARIAD; Research grant/Funding (institution): Baxalta GMBH/ Servier Affaires; Research grant/Funding (institution): Guardanth health; Research grant/Funding (institution): Puma; Research grant/Funding (institution): Piqur. J. O'Shaughnessy: Honoraria (self): Abbive; Honoraria (self): Agendia; Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Celgene; Honoraria (self): Eisai; Honoraria (self): Genentech; Honoraria (self): Immunomedics; Honoraria (self): Jounce Therapeutics; Honoraria (self): Eli Lilly; Honoraria (self): Merck Sharpe & Dohme; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Puma Biotechnology; Honoraria (self): Roche; Honoraria (self): Seattle Genetics. V.C. Dieras: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Eli Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Seattle Genetics. L.A. Carey: Research grant/Funding (institution): Innocrin Pharma; Research grant/Funding (institution): Syndax; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution), Non-remunerated activity/ies: Novartis; Research grant/Funding (institution): NanoString Technologies; Licensing/Royalties, Spouse/Financial dependant: Falcon Therapeutics; Non-remunerated activity/ies: Sanofi-Aventis; Non-remunerated activity/ies: G1 Therapeutics; Non-remunerated activity/ies: Genentech/Roche; Non-remunerated activity/ies: GlaxoSmithKline. L. Gianni: Advisory/Consultancy, Travel/Accommodation/Expenses, Licensing/Royalties: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Synaffix; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: ADC Therapeutics; Advisory/Consultancy: Odonate Therapeutics; Advisory/Consultancy: Oncolytics; Advisory/Consultancy: Genenta; Advisory/Consultancy: Sandoz; Advisory/Consultancy: MetIS; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Revolution Medicine; Advisory/Consultancy, Research grant/Funding (institution): Zymeworks; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: Genentech; Advisory/Consultancy: Onkaido Therapeutics; Advisory/Consultancy: Taiho Pharmaceutical; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Synthon; Advisory/Consultancy: FortySeven; Travel/Accommodation/Expenses: Chugai Pharmaceutical. M. Piccart: Honoraria (self), Research grant/Funding (self): Immunomedics; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): Camel-IDS; Honoraria (self): Crescendo Biologics; Honoraria (self): Debiopharm; Honoraria (self): G1 Therapeutics; Honoraria (self), Research grant/Funding (self): Roche-Genentech; Honoraria (self): Huya; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self): Menarini; Honoraria (self), Research grant/Funding (self): Merck Sharp & Dohme; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self): Odonate; Honoraria (self): Periphagen; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self): Seattle Genetics; Research grant/Funding (self): Radius; Research grant/Funding (self): Servier; Research grant/Funding (self): Synthon. S. Loibl: Honoraria (institution), Research grant/Funding (self): AbbVie; Honoraria (institution), Research grant/Funding (self): Amgen; Honoraria (institution), Research grant/Funding (self): AstraZeneca; Honoraria (institution), Research grant/Funding (self): Celgene; Honoraria (institution), Research grant/Funding (self): Novartis; Honoraria (institution), Research grant/Funding (self): Pfizer; Honoraria (institution), Research grant/Funding (self): Roche; Honoraria (institution): Seattle Genetics; Honoraria (institution): PriME/ Medscape; Honoraria (self): Chugai; Honoraria (self): Teva; Honoraria (self): Vifor; Honoraria (institution), Research grant/Funding (self): Daiichi-Sankyo; Honoraria (institution): Eli Lilly; Honoraria (institution): Samsung; Advisory/Consultancy, Advisory fee paid to institute: Eirgenix; Advisory/Consultancy, advisory fee paid to institute: Bristol-Myers Squibb; Advisory/Consultancy, Advisory fee paid to institute: Puma; Honoraria (institution): Merck Sharp & Dohme; Research grant/Funding (self): Immunomedics; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0 pending. D. Goldenberg: Shareholder/Stockholder/Stock options, Licensing/Royalties: Immunomedics; Leadership role: Center for Molecular Medicine & Immunology. Q. Hong M.S. Olivo: Full/Part-time employment: Immunomedics. L.M. Itri: Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: The Medicines Company; Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunomedics; Spouse/Financial dependant: Memorial Sloan Kettering Cancer Institute. S.A. Hurvitz: Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): OBI Pharma; Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution): Dignitana; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Biomarin; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Marcogenics; Research grant/Funding (institution): Ambryx; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Pieris; Research grant/Funding (institution): Radius; Research grant/Funding (institution): Arvinas.