Study Design

DESTINY-Breast07: Study Design

Study of T-DXd in Combination With Other Anticancer Agents for Patients With HER2 Positive, Advanced, or Metastatic BC
Key Eligibility Criteria

Study of T-DXd in Combination With Other Anticancer Agents for Patients With HER2 Positive, Advanced, or Metastatic BC

Study of T-DXd in Combination With Other Anticancer Agents for Patients With HER2 Positive, Advanced, or Metastatic BC^1-4

DESTINY-Breast07 is a 2-part, Phase Ib/II, multicenter, open-label, modular, dose‑finding (Part 1) and dose-expansion (Part 2) study to evaluate the safety, tolerability, and preliminary anti-tumor activity of T-DXd combined with other anticancer agents in patients HER2 positive (IHC 3+ or IHC 2+/ISH+) advanced/unresectable or metastatic BC.^1-4

Study Design and Endpoints^1-4

<p>Study Design and Endpoints<span class="tooltip"><span class="tooltip-text"><sup>1-4</sup></span><span class="tooltip-content" style="display: none;"><span>1. André F, Hamilton E, Loi S, et al. Trastuzumab deruxtecan (T-DXd) combinations in patients with HER2-positive advanced or metastatic breast cancer: a phase 1b/2, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast07). Presented at American Society of Clinical Oncology (ASCO) Virtual Meeting; June 4-8, 2021; Chicago, Illinois. Poster TPS1096.</span><span>2. AstraZeneca. A phase 1b/2 study of T-DXd combinations in HER2-positive metastatic breast cancer (DB-07) . ClinicalTrials.gov website. <a target="_blank" href="https://www.clinicaltrials.gov/ct2/show/NCT04538742">https://www.clinicaltrials.gov/ct2/show/NCT04538742</a></span><span>3. Hamilton EP, Jhaveri KL, Loi S, et al. Dose-expansion study of trastuzumab deruxtecan as monotherapy or combined with pertuzumab in patients with metastatic human epidermal growth factor receptor-2 positive (HER2+) breast cancer in DESTINY-Breast07 (DB-07) [poster]. Poster presented at: San Antonio Breast Cancer Symposium (SABCS) 2022 Annual Meeting; December 6-10,2022; San Antonio, Texas. Poster PD18-11.</span><span>4. Anders CP, Loi S, Hamilton E, et al. Safety, tolerability, and antitumor activity of T-DXd in patients with HER2-positive mBC and active brain metastases in DESTINY-Breast07. Poster 185P. Presented at European Society for Medical Oncology-Breast Cancer (ESMO-BC) Annual Meeting; May 15-17, 2024; Berlin, Germany.</span></span></span></p>

^aPD-L1 positive is defined as IHC ≥1%

^bArm not initiated in Part 1 and Part 2

^cThe part 2 dose-expansion phase will use the RP2D determined in part 1

^dArm not initiated in part 2. ^eBased on investigator assessment per RECIST version 1.1

^fBased on investigator assessment per RECIST version 1.1 or death by any cause

^gStable and active brain metastases only

Key Eligibility Criteria

Key Eligibility Criteria^1-3,5

Key Eligibility Criteria in DESTINY-Breast07.

Inclusion Criteria	Exclusion Criteria
Adults aged ≥18 years	Uncontrolled or significant cardiovascular disease
Pathologically documented BC that is advanced/unresectable or metastatic, HER2 positive (locally confirmed as IHC 3+ or IHC 2+/ISH+), and documented as HR positive or HR negative in the metastatic setting	Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
Adequate tumor sample from the metastatic setting for biomarker assessment	Lung-specific intercurrent clinically significant illnesses
ECOG PS of 0 or 1	Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
Part 1: disease progression on or after the last systemic therapy prior to starting study treatment Part 1: received ≥1 prior treatment line in metastatic setting	Spinal cord compression or a history of leptomeningeal carcinomatosis
Part 2 (Modules 0-5): received no prior lines of therapy for advanced/metastatic BC Part 2 (Modules 6-7): received <1 prior line of therapy for advanced/metastatic BC	Prior treatment with an immune checkpoint inhibitor, an ADC containing a topoisomerase I inhibitor, or tucatinib
CNS Inclusion	CNS Exclusion
Modules 0-5: No BM or previously treated stable BM	Modules 0-5: Untreated BM
Modules 6-7: Untreated BM not needing local therapy or previously treated BM that have progressed since prior local therapy	Modules 6-7: Ongoing use of systemic corticosteroids for control of symptoms of BM or brain lesion thought to require immediate local therapy

Abbreviations

ADA = anti-drug antibody

;

ADC = antibody drug conjugate

;

AE = adverse event

;

BC = breast cancer

;

BM = brain metastases

;

CANTAB = Cambridge Neuropsychological Test Automated Battery

;

CNS = central nervous system

;

DOR = duration of response

;

ECOG PS = Eastern Cooperative Oncology Group Performance Status

;

HER2 = human epidermal growth factor receptor 2

;

HR = hormone receptor

;

IHC = immunohistochemistry

;

ILD = interstitial lung disease

;

ISH = in-situ hybridization

;

IV = intravenous

;

MDASI-BT = MD Anderson Symptom Inventory Brain Tumor

;

NANO = Neurologic Assessment in Neuro-Oncology

;

ORR = objective response rate

;

OS = overall survival

;

PD-L1 = programmed cell death-ligand 1

;

PFS = progression-free survival

;

PFS2 = progression-free survival after next-line treatment

;

PK = pharmacokinetics

;

RECIST = Response Evaluation Criteria in Solid Tumours

;

RP2D = recommended phase 2 dose

;

T-DXd = trastuzumab deruxtecan

References

1. André F, Hamilton E, Loi S, et al. Trastuzumab deruxtecan (T-DXd) combinations in patients with HER2-positive advanced or metastatic breast cancer: a phase 1b/2, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast07). Presented at American Society of Clinical Oncology (ASCO) Virtual Meeting; June 4-8, 2021; Chicago, Illinois. Poster TPS1096.

2. AstraZeneca. A phase 1b/2 study of T-DXd combinations in HER2-positive metastatic breast cancer (DB-07) . ClinicalTrials.gov website. https://www.clinicaltrials.gov/ct2/show/NCT04538742

3. Hamilton EP, Jhaveri KL, Loi S, et al. Dose-expansion study of trastuzumab deruxtecan as monotherapy or combined with pertuzumab in patients with metastatic human epidermal growth factor receptor-2 positive (HER2+) breast cancer in DESTINY-Breast07 (DB-07) [poster]. Poster presented at: San Antonio Breast Cancer Symposium (SABCS) 2022 Annual Meeting; December 6-10,2022; San Antonio, Texas. Poster PD18-11.

4. Anders CP, Loi S, Hamilton E, et al. Safety, tolerability, and antitumor activity of T-DXd in patients with HER2-positive mBC and active brain metastases in DESTINY-Breast07. Poster 185P. Presented at European Society for Medical Oncology-Breast Cancer (ESMO-BC) Annual Meeting; May 15-17, 2024; Berlin, Germany.

5. André F, Hamilton EP, Loi S, et al. Dose-finding and -expansion studies of trastuzumab deruxtecan in combination with other anticancer agents in patients with advanced/metastatic HER2+ (DESTINY-Breast07) and HER2-low (DESTINY-Breast08) breast cancer [poster, supplement, and abstract]. Poster presented at: American Society of Clinical Oncology (ASCO) 2022 Congress; June 3-5, 2022; Chicago, IL. J Clin Oncol. 2022;40(suppl 16). Abs 3025.

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: 325e86bc-2a1f-401a-b8d6-fa304896a85b
Last updated: 14-February-2023

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