Clinical Trial Protocol

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

*Author for correspondence: Tel.: +1 507 293 0526;

E-mail Address: osullivan.ciara@mayo.edu

https://orcid.org/0000-0001-6069-9800

Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA

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Karla V Ballman

Alliance Statistics & Data Center, Weil Cornell Medicine, NY 10065, USA

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Linda McCall

Alliance Statistics & Data Center, Duke University, Durham, NC 27708, USA

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Anuhya Kommalapati

Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA

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Tyler Zemla

Alliance Statistics & Data Center, Mayo Clinic, Rochester, MN 55905, USA

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Anna Weiss

Division of Breast Surgery, Department of Surgery, Brigham & Women's Hospital, Boston, MA 02115, USA

Breast Oncology Program, Dana-Farber/Brigham & Women's Cancer Center, Boston, MA 02115, USA

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Melissa Mitchell

Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

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Victoria Blinder

Department of Psychiatry & Behavioral Sciences, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, NY 10065, USA

Department of Medicine, Memorial Sloan Kettering Cancer Center, NY 10065, USA

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Nadine M Tung

Beth Israel Deaconess Medical Center, Boston, MA 02215, USA

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William J Irvin

Department of Medical Oncology, Bon Secours Cancer Institute, Midlothian, VA, USA

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Myounghee Lee

Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA

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Matthew P Goetz

Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA

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William Fraser Symmans

Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

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Virginia F Borges

Division of Medical Oncology, Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA

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Ian Krop

Department of Medical Oncology, Dana-Farber/Partners Cancer Care, Boston, MA, USA

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Lisa A Carey

Department of Medical Oncology, UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

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Ann H Partridge

Department of Medical Oncology, Dana-Farber/Partners Cancer Care, Boston, MA, USA

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Published Online:12 Oct 2021https://doi.org/10.2217/fon-2021-0753

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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.

Lay abstract

In this research study (A011801; CompassHER2 RD), patients with early stage HER2-positive breast cancer who already received treatment with chemotherapy and anti-HER2 targeted therapies followed by surgery are mainly enrolled. If cancer is still present in the breast and/or lymph nodes at the time of surgery, there is a higher risk of a recurrence in the future, and enrollment on A011801 is an option. Usually, if there is tumor remaining after chemotherapy and anti-HER2 targeted therapies, the main treatment is the use of an FDA-approved intravenous drug called T-DM1. Additional treatment may also include radiotherapy and/or medications to block the activity of estrogen. The usual treatment approach reduces the likelihood of breast cancer recurring in the future. This study has been performed to answer the following question: Is the combination of T-DM1 and a newer drug tucatinib better than usual treatment with T-DM1 alone at preventing cancer from returning? Study participants will receive treatment with T-DM1 and placebo (a pill that looks like the study drug but contains no medication) or T-DM1 and tucatinib, for up to 14 cycles, unless their breast cancer returns or the side effects become too severe. Research bloods are taken on study along with standard blood work, and we also request a stored tumor sample from the original biopsy and from the breast cancer surgery for research purposes. Optional Quality of Life Questionnaires are also included in the trial. After the study, participants finish T-DM1 and placebo, or T-DM1 and tucatinib, and their doctor will continue to follow their condition with clinic visits every 6 months for 10 years and watch for side effects and for signs of breast cancer recurring.

Clinical Trial Registration:NCT04457596 (ClinicalTrials.gov).

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 17, No. 34

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History

Received 17 June 2021

Accepted 17 September 2021

Published online 12 October 2021

Published in print December 2021

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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.

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