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DESTINY-Breast01: Study Design

Study Design

Study of T-DXd in Patients With Unresectable/Metastatic BC1-3

DESTINY-Breast01 is an ongoing, Phase II, open-label, multicenter, 2-part study evaluating the efficacy and safety of T-DXd, in patients with HER2 positive unresectable and/or metastatic BC previously treated with T‑DM1. HER2 positive is defined as IHC 3+ or IHC 2+/ ISH+ as assessed by central testing based on archival samples. Part 1 consisted of a PK and dose finding stage to determine the RP2D and Part 2 enrolled additional patients at the RP2D1

Study Design.1-3

Study Design.1-3

Endpoints1-3

Primary: 

  • Confirmed ORR, independent central imaging facility review assesseda

Secondary: 

  • Efficacy: DOR, PFS, OS, DCR, CBR, Change in SLD of measurable tumors, and ORR (investigator assessed)a
  • Safety: SAEs, TEAEsb, AESIs, Elevated troponin levels, Physical examination findingsc, Vital sign measurements and standard clinical laboratory parameters, ECG parameters and ECHO/MUGA findings, Ophthalmologic findings, ADA
  • PK (evaluated during Cycles 1 and 3): Cmax, Tmax, AUClast, AUC0-21d, AUCinf, T1/2, CL, Vss, Serum concentrationsd

Exploratory:

  • Efficacy: duration of stable disease, time to response, exposure-response relationships
  • PK: potential biomarker response (eg: HER2 extracellular domain)

aBased on RECIST V1.1; bIncluding those leading to discontinuation; cIncluding ECOG PS; dNot limited to Cycle 1.

Median Duration of Follow-Up1-3

  • August 1, 2019 DCO: 11.1 months (range, 0.7-19.9 months)1
  • June 8, 2020 DCO: 20.5 months (range, 0.7-31.4 months)2
  • March 26, 2021 DCO: 26.5 months (range, 0.7-39.1 months)3

Key Eligibility Criteria

Key Eligibility Criteria1

Key Eligibility Criteria in DESTINY-Breast01.1
Key Inclusion CriteriaKey Exclusion Criteria
  • Age ≥18 years (subject to local regulatory requirements)
  • Uncontrolled or significant cardiovascular disease
  • Pathologically documented BC that is unresectable or metastatic, was previously treated with T-DM1, and has HER2 positive expression confirmed per protocol
  • QTc prolongation to >450 ms in men and >470 ms in women
  • ≥1 measurable lesion per RECIST V1.1
  • LVEF <50%
  • Protocol-defined adequate bone marrow, renal, and hepatic function
  • Medical history of (non-infectious) ILD/pneumonitis that required steroids or active or suspected ILD/pneumonitis
 
  • BM that are untreated, symptomatic, or require therapy to control symptoms as well as any history of radiation, surgery, or other therapy (including steroids or anticonvulsants) to control symptoms from BM within 60 days of randomization

Note: Criteria listed are common to both Parts 1 and 2 of the study. 


Abbreviations

ADA = anti-drug antibody

;

AESI = adverse events of special interest

;

BC = breast cancer

;

BM = brain metastases

;

CBR = clinical benefit rate

;

DCO = data cut-off

;

DCR = disease control rate

;

DOR = duration of response

;

ECG = electrocardiogram

;

ECHO = echocardiogram

;

ECOG = Eastern Cooperative Oncology Group

;

HER2 = human epidermal growth factor receptor 2

;

IHC = immunohistochemistry

;

ILD = interstitial lung disease

;

ISH = in situ hybridization

;

LVEF = left ventricular ejection fraction

;

MUGA = multigated acquisition scan

;

PK = pharmacokinetics

;

PFS = progression-free survival

;

PS = performance status

;

ORR = objective response rate

;

OS = overall survival

;

R = randomization

;

RECIST = Response Evaluation Criteria in Solid Tumors

;

RP2D = recommended phase 2 dose

;

SAE = serious adverse event

;

SLD = sum of longest diameters

;

T-DM1 = trastuzumab emtansine

;

T-DXd = trastuzumab deruxtecan

;

TEAE = treatment emergent adverse event

References

1. Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med 2020;382:610-621.
2. Modi S, Saura C, Yamashita T, et al. Updated results from DESTINY-Breast01, a phase 2 trial of trastuzumab deruxtecan (T-DXd) in HER2-positive metastatic breast cancer [poster and abstract]. Poster presented at: San Antonio Breast Cancer Symposium; December 8-11, 2020. Cancer Res. 2021;81(suppl 4). Abstract PD3-06.
3. Saura C, Modi S, Krop I, et al. Trastuzumab Deruxtecan (T-DXd) in patients with HER2-positive metastatic breast cancer: updated survival results from a phase 2 trial (DESTINY-Breast01) [poster and abstract]. Poster presented at: European Society for Medical Oncology (ESMO) 2021 Annual Meeting; September 16-21, 2021. Ann Oncol. 2021;32(suppl 5). Abstract 279P.

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