DESTINY-Breast 06

BOOG 2020-01

General Information

BOOG number

BOOG 2020-01


DESTINY-Breast 06


Date: 22/12/2022

Inclusion closed


Participating parties / group

Daiichi - AstraZeneca

Other study number


Full title

A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (T-DXd) versus Investigator’s Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Breast Cancer Patients whose Disease has Progressed on Endocrine Therapy in the Metastatic Setting (DESTINY-Breast06)



Any HER2, HR+


Trastuzumab Deruxtecan

Target sample size

850 (wereldwijd)

Actual accrual

NL: 13; Wereldwijd: 834
Date: 22/12/2022

Estimated study completion date





Study manager


Central datamanagement and randomization







A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (T-DXd) Versus Investigator’s Choice Chemotherapy.

Op 22Dec’22 is de IHC >0 <1+ subgroupgesloten voor screening.

Op15Dec’22 is de IHC2+ subgroep gesloten voor screening.

Op 28Oct’22 is de IHC1+ subgroep gesloten voor recruitment.

Participating sites

  • NKI-AvL
  • Erasmus MC
  • Zuyderland MC
  • Amphia ziekenhuis
  • MC Leeuwarden
  • Ziekenhuisgroep Twente


Primary study objectives:

  • To assess the efficacy of trastuzumab deruxtecan compared to chemotherapy on progression free survival (PFS) of the population


Secondary study objectives:

  • Assess the efficacy of trastuzumab deruxtecan compared to chemotherapy on overall survival (OS) of the population
  • Assess the efficacy of trastuzumab deruxtecan compared to chemotherapy on overall survival (OS) in the HER2 ICH>0<1 sub-group
  • Compare the 2 treatment arms in terms of ORR, DoRPFS2, TFST, TSST, HRQoL
  • Assess the safety of trastuzumab deruxtecan
  • Investigate the PK and immunogeneticity of trastuzumab deruxtecan


Exploratory study objectives:

  • To collect blood and tissue samples for defining biological responses to trastuzumab deruxtecan and identifying candidate markers that may correlate with likelihood of clinical benefit
  • To explore the impact of treatment and disease state on health utility using the EQ-5D-5L To assess patient-reported treatment tolerability
  • To assess the patient’ overall impression of the severity of their cancer symptoms and change in condition since starting the study
  • To explore the impact of treatment and disease on health care resource use
  • To explore optimize technologies for detection of HER2 protein expression


Progression Free Survival (PFS) – in HR+, HER2-low populaton

Eligibility Criteria

Key Inclusion Criteria:

• Patients must be ≥18 years of age.

• Pathologically documented breast cancer that:

1. is advanced or metastatic

2. has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- oruntested) or HER2 IHC 0 (ISH- or untested)

3. has HER2-low or HER2 IHC >0 <1+ expression as determined by central HER2 laboratory result established on a tissue sample taken in the metastatic setting

4. was never previously HER2-positive

5. is documented HR+ disease in the metastatic setting.

6. No prior chemotherapy for advanced or metastatic breast cancer.

7. Has adequate tumor samples for assessment of HER2 status

8. Must have either:

a. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or;

b. disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting (progression ofdisease within 24 months on adjuvant ET is considered a line of therapy)

9. Has protocol-defined adequate organ and bone marrow function.


Key Exclusion Criteria:

  • Ineligible for all options in the investigator’s choice chemotherapy arm
  • Uncontrolled intercurrent illness or significant cardiovascular disease
  • Active or prior documented ILD/pneumonitis or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
  • Lung-specific intercurrent clinically significant illnesses
  • Patients with spinal cord compression or clinically central nervous system metastasis

Regulatory Information

CCMO approval

Date: 01/02/2021
Nr: NL73583.056.20

EC approval


EudraCT number