Abstract 265TiP
Background
Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) containing a TROP2-directed antibody bound to a topoisomerase I inhibitor payload through a chemically hydrolysable CL2A linker. SG is approved for the treatment of metastatic triple-negative breast cancer (mTNBC) patients (pts) after two or more systemic therapies, including at least one of them for advanced disease; and for pts with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (mBC) who have received endocrine-based therapy (ET) and two additional systemic therapies. To date, no biomarkers, including TROP2 protein levels, have shown a clinical utility to predict TROP2-directed treatment benefit, warranting the identification of biomarkers of response to SG and the understanding of key resistance mechanisms to the drug. ACROSS-TROP2 aims to address this unmet medical need.
Trial design
ACROSS-TROP2 (NCT06236269) is an open-label, single arm, phase II study in pts with HR+/HER2- mBC treated with SG. It will include 50 pre- or post-menopausal female or male pts who have progressed on prior CDK4/6i plus ET and who have received up to 1 prior regimen of chemotherapy or ADC for mBC. Pts will receive SG at 10 mg/kg as an IV infusion on Days 1 and 8 of a 21-day cycle until disease progression (PD). Paired fresh biopsies before start of treatment (baseline), after 2-3 weeks of treatment (C2D1), and at PD will be collected. The primary objective is to evaluate the change in CelTIL score between baseline and C2D1 tumor samples. CelTIL, which correlates with long term efficacy outcomes, is a composite score of tumor cellularity and tumor-infiltrating lymphocytes. Secondary objectives include overall response rate, progression-free survival, duration of response, time to response, safety, and tolerability. Further correlative molecular analyses will be carried out in both tissue and blood samples collected throughout the treatment. The study will utilize a paired sample t-test to assess whether the mean change in CelTIL score is statistically different from zero. The study has been approved in Spain and is ongoing in 10 sites across SOLTI network.
Clinical trial identification
NCT06236269.
Legal entity responsible for the study
SOLTI Cancer Research Group.
Funding
Gilead Sciences, Inc.
Disclosure
E.M. Ciruelos: Financial Interests, Personal, Other, Speakers Bureau. Educational activities: Roche; Financial Interests, Personal, Invited Speaker, Symposia and Educational activities: Roche; Financial Interests, Personal, Advisory Board, Non-permanent advisor: Roche, Lilly, Novartis, Pfizer, Daiichi Sankyo, MSD; Financial Interests, Personal, Invited Speaker, Symposia and Education: Lilly; Financial Interests, Personal, Invited Speaker, Educational activities: Pfizer; Financial Interests, Personal, Advisory Board, Non-permanent advisor, Travel accommodation: AstraZeneca; Financial Interests, Personal, Other, Advisory Board: Gilead; Financial Interests, Personal, Other, Advisory Board, Invited speaker: Seagen; Financial Interests, Institutional, Funding, PI for Patricia 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for Prometeo 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for TATEN trial (sponsor: SOLTI Group): MSD; Financial Interests, Institutional, Funding, PI for ATREZZO trial (sponsor: SOLTI Group): Roche; Non-Financial Interests, Member of Board of Directors, Non-profit organization dedicated to breast cancer research: SOLTI Cooperative Group; Non-Financial Interests, Advisory Role, Scientific Evaluator at ISCIII (Spanish Government Academic Research Platform): Instituto de Salud Carlos III. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer/ AstraZeneca / Veracyte / Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech, Novartis. R. Villanueva Vazquez: Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Other, Congress attendance registration: Pfizer, Novartis, Gilead, AstraZeneca, Daiichi Sankyo/AstraZeneca. J.M. Cejalvo: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Lilly, AstraZeneca, Gilead. F.J. Salvador Bofill: Non-Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Pfizer, Astra Zene, Daiichi Sankyo; Non-Financial Interests, Personal, Advisory Board: Lilly, Novartis, Pfizer, Astra Zene, Daiichi Sankyo; Non-Financial Interests, Personal, Speaker’s Bureau: Lilly, Novartis, Pfizer, Astra Zene, Daiichi Sankyo. I. Blancas López-Barajas: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Eisai, Gilead, Grünenthal, GSK, Lilly, MSD, Novartis, Pfizer, Pierre-Fabre, Roche, Seagen; Financial Interests, Personal, Other, Medical monitor: Medical Science Innovation Research (MEDSIR); Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Roche, Agendia; Financial Interests, Institutional, Research Grant: Pfizer; Other, Support for attending meetings and/or travel: AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Lilly, Novartis, Pfizer, Roche, Pierre Fabre. A. Ferrando Diez: Financial Interests, Personal, Invited Speaker: MSD. Y. Izarzugaza Peron: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Gilead, AstraZeneca; Financial Interests, Personal, Expert Testimony: Daiichi. G. Villacampa Javierre: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabrer, GSK; Financial Interests, Personal, Invited Speaker, Internal discussion about the interpretation of some published results: Pfizer; Financial Interests, Personal, Other, Collaborations with specific projects: Reveal Genomics. M. Oliveira: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo / AstraZeneca, Gilead, Lilly, MSD, Relay Therapeutics, Roche, Seagen, Cureo Science, iOne, Pfizer; Financial Interests, Personal, Invited Speaker: Eisai, Gilead, Pfizer, Roche, Seagen, AstraZeneca, Lilly, Medscape, AstraZeneca, AstraZeneca; Financial Interests, Personal, Other, Educational activity: Libbs; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, GSK, Roche, Seattle Genetics, Zenith Epigenetics, Gilead, Ayala Pharmaceuticals, Pfizer; Financial Interests, Invited Speaker: Roche; Non-Financial Interests, Member of Board of Directors, Head: SOLTI Breast Cancer Research; Other, Travel Grant: Pierre Fabre, Eisai, Gilead, AstraZeneca. All other authors have declared no conflicts of interest.