Study Design

DESTINY-Breast06: Study Design

Study Design
Key Eligibility Criteria

Study Design

Study of T-DXd vs Physician’s Choice Chemotherapy in Patients With HR+, HER2-Low or HER2-ultralow Metastatic Breast Cancer With Prior Endocrine Therapy¹

DESTINY-Breast06 (NCT04494425) is a phase 3, open-label, multicenter, randomized study being conducted to evaluate the efficacy, safety, and tolerability of T-DXd compared with TPC (paclitaxel, nab-paclitaxel, or capecitabine) in chemotherapy-naive patients with HR+ HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer whose disease has progressed on ≥1 prior line of ET in the metastatic setting.^1,2
A total of 866 patients were randomly assigned 1:1 to receive either T-DXd (n = 436) or TPC (n = 430).¹

DESTINY-Breast06 Study Design¹

<p>DESTINY-Breast06 Study Design<span class="tooltip"><span class="tooltip-text"><sup>1</sup></span><span class="tooltip-content" style="display: none;"><span>1. Curigliano G, Hu X, Dent R, et al. Trastuzumab deruxtecan vs physician’s choice of chemotherapy in patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–low or HER2-ultralow metastatic breast cancer with prior endocrine therapy: primary results from DESTINY-Breast06. Presented at 2024 ASCO Annual Meeting; May 31-June 4, 2024; Chicago, Illinois. Presentation LBA1000.</span></span></span></p>

^aStudy enrollment was based on central HER2 testing. HER2 status was determined based on the most recent evaluable HER2 IHC sample prior to randomization; HER2-ultralow defined as faint, partial staining of the membrane in ≤10% of tumor cells (also known as IHC >0<1+).

^bHER2-ultralow status as determined by IRT data (note: efficacy analyses in the HER2-ultralow subgroup were based on n = 152 as determined per central laboratory testing data).

^cTo be presented separately.

Key Eligibility Criteria

Key Eligibility Criteria²

Key Eligibility Criteria in DESTINY-Breast06

Key Inclusion Criteria	Key Exclusion Criteria
≥18 years of age	Ineligible for all investigator’s choice chemotherapy arms
Pathologically documented breast cancer that Is advanced or metastatic Has a history of HER2-low (IHC 1+ or IHC 2+/ISH−) or negative expression (IHC 0) Is advanced or metastatic Has HER2-low or HER2-ultralow (IHC 0 with membrane staining) expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting Was never previously HER2+ Is documented HR+ in the metastatic setting	Lung-specific intercurrent clinically significant illnesses
No prior chemotherapy for advanced or metastatic breast cancer	Uncontrolled or significant CVD or infection
Has adequate tumor samples for assessment of HER2 status	Prior documented ILD/pneumonitis that required steroids or active or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
Has disease progression within 6 months of starting first-line metastatic treatment with an ET combined with a CDK4/6i or disease progression on ≥2 previous lines of ET with or without a targeted therapy in the metastatic setting*	Spinal cord compression or active CNS metastases
Protocol-defined adequate organ and bone marrow function	Prior participation in a previous T-DXd study regardless of treatment received
	Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow-up period of a prior interventional study

*Disease recurrence while on the first 24 months of starting adjuvant ET will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting.

Abbreviations

BICR = blinded independent central review

;

CDK4/6i = cyclin-dependent kinase 4/6 inhibitor

;

CNS = central nervous system

;

CVD = cardiovascular disease

;

DOR = duration of response

;

ET = endocrine therapy

;

HER2 = human epidermal growth factor receptor 2

;

HR = hormone receptor

;

IHC = immunohistochemistry

;

ILD = interstitial lung disease

;

INV = investigator assessed

;

IRT = interactive response technology

;

ISH = in situ hybridization

;

ITT = intent-to-treat

;

mBC = metastatic breast cancer

;

ORR = objective response rate

;

OS = overall survival

;

PFS = progression-free survival

;

Q3W = every 3 weeks

;

R = randomization

;

RECIST = Response Evaluation Criteria in Solid Tumors

;

T-DXd = trastuzumab deruxtecan

;

TPC = treatment of physician's choice

References

1. Curigliano G, Hu X, Dent R, et al. Trastuzumab deruxtecan vs physician’s choice of chemotherapy in patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–low or HER2-ultralow metastatic breast cancer with prior endocrine therapy: primary results from DESTINY-Breast06. Presented at 2024 ASCO Annual Meeting; May 31-June 4, 2024; Chicago, Illinois. Presentation LBA1000.

2. AstraZeneca. Study of trastuzumab deruxtecan (T-DXd) vs investigator's choice chemotherapy in HER2-low, hormone receptor positive, metastatic breast cancer (DB-06). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT04494425

Please note that this content may contain some data and/or patient populations which are considered off-label in your country. Providing this information does not constitute any recommendation for use. AstraZeneca is providing this material as an information service and professional courtesy.

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Document ID: c791d159-0a5c-4180-b38f-cd5e26050804
Last updated: 28-June-2024

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