Alliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer

Abstract

This report describes the rationale, purpose and design of A011801 (CompassHER2 RD), an ongoing prospective, multicenter, Phase III randomized trial. Eligible patients in the United States (US) and Canada with high-risk (defined as ER-negative and/or node-positive) HER2-positive (HER2+) residual disease (RD) after a predefined course of neoadjuvant chemotherapy and HER2-directed treatment are randomized 1:1 to adjuvant T-DM1 and placebo, versus T-DM1 and tucatinib. Patients have also received adjuvant radiotherapy and/or endocrine therapy, if indicated per standard of care guidelines. The primary objective of the trial is to determine if the invasive disease-free survival (iDFS) with T-DM1 plus tucatinib is superior to iDFS with T-DM1 plus placebo; other outcomes of interest include overall survival (OS), breast cancer-free survival (BCFS), distant recurrence-free survival (DRFS), brain metastases-free survival (BMFS) and disease-free survival (DFS). Correlative biomarker, quality of life (QoL) and pharmacokinetic (PK) end points are also evaluated.

Trial registration: ClinicalTrials.gov NCT04457596.

Keywords: HER2-positive early breast cancer; T-DM1; postneoadjuvant; residual disease; tucatinib.

Conflict of interest statement

Financial & competing interests disclosure

Research reported in this publication was supported by the National Cancer Institute of the NIH under award numbers: U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA233180, UG1CA233290, UG1CA233329, UG1CA233373 and UG1CA232760. https://acknowledgments.alliancefound.org. Also supported in part by Seagen. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Dr O'Sullivan has received research funding to institution from Eli Lilly, Sermonix, Bavarian Nordic and Seagen Inc. Dr Goetz reports other from Eagle pharmaceuticals, other from Lilly, other from Biovica, other from Novartis, other from Sermonix, grants from Pfizer, grants from Lilly, other from Pfizer, other from Biotheranostics, grants from Sermonix, other from AstraZeneca, other from Blueprint Medicines, other from Research to Practice, other from Clinical Education Alliance, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.. A011801 (CompassHER2 RD) study scheme.

1 cycle = 21 days. HR: Hormone receptor; RD: Residual disease.