Table 2.

Ongoing clinical trials evaluating trastuzumab deruxtecan in patients with breast cancer

Register number (target accrual, N)	Design; arms and regimen	Study population	Primary outcome	Status/results
DESTINY-Breast02 NCT03523585 N = 600	Phase III; open label, randomizing to one of two arms: T-Dxd vs. TPC	HER2-positive MBC; previously treated with T-DM1	PFS	Accruing
DESTINY-Breast03 NCT03529110 N = 500	Phase III; open label, randomizing to one of two arms: T-Dxd vs. T-DM1	HER2-positive MBC; progressed during (or <6 months after) a trastuzumab/taxane-based regimen in the adjuvant or metastatic setting	PFS	Completed accrual; results pending
NCT04539938 N = 70	Phase II; single arm: tucatinib plus T-Dxd	HER2-positive MBC; previously treated (two or more prior HER2-based regimens in the metastatic setting)	ORR	Accruing
DESTINY-Breast07 NCT04538742 N = 350	Phase I dose escalation (part1) and dose expansion (part 2). Single-arm, four cohorts (T-Dxd with one of these four regimens: durvalumab, pertuzumab, paclitaxel, pertuzumab plus paclitaxel)	HER2-positive MBC; part 1—disease progression on or after the last systemic therapy prior to starting study treatment. At least one prior treatment line in metastatic setting required. Part 2—no prior lines of therapy for advanced/MBC allowed	Occurrence of AEs and serious AEs (part 1 and 2)	Not yet recruiting
DESTINY-Breast05 NCT04622319 N = 1600	Phase III; open label, randomizing to one of two arms: T-Dxd vs. T-DM1	HER2-positive early-stage with residual disease following neoadjuvant chemotherapy containing trastuzumab and taxane	IDFS	Not yet recruiting
DESTINY-Breast04 NCT03734029 N = 540	Phase III; open label, randomizing to one of two arms: T-Dxd vs. TPC	HER2-low (IHC 1+ or 2+/FISH-negative) MBC. One to two prior CT for metastatic breast cancer	PFS	Accruing
DESTINY-Breast 06 NCT04494425 N = 850	Phase III; open label, randomizing to one of two arms: T-Dxd vs. TPC	HR+/HER2-low (IHC 1+ or 2+/FISH-negative) MBC. No prior CT for advanced BC or MBC	PFS	Accruing
NCT04553770 N = 88	Phase II, open label, randomizing to one of two arms: T-Dxd or T-Dxd plus anastrozole	Early-stage HR+/HER2-low (IHC 1+ or 2+/FISH-negative). Candidate for neoadjuvant therapy	pCR rate	Not yet recruiting
DESTINY-Breast 08 NCT04556773 N = 185	Phase I dose escalation (part 1) and dose expansion (part 2). Single-arm, five cohorts (T-Dxd with one of these five regimens: durvalumab plus paclitaxel, capivasertib, anastrozole, fulvestrant, capecitabine)	HER2-low BC	Occurrence of AEs (part 1) and serious AEs (part 2)	Not yet recruiting
BEGONIA NCT03742102 N = 57a	Phase Ib/II, single-arm, multicohort; arm 6-durvalumab plus T-Dxd	HER2-low BC	Incidence of AEs (part 1); ORR (part 2)	Accruing
DEBBRAH NCT04420598 N = 39	Phase II, single arm; T-Dxd monotherapy	HER2-positive BC or HER2-low BC with brain metastasis or leptomeningeal dissemination	Efficacy (depending on the arm PFS, ORR, OS)	Accruing
NCT03523572 N = 99	Phase Ib, single arm T-Dxd plus nivolumab; part 1—dose escalation; part 2—dose expansion	HER2-positive BC, HER2-low BC and urothelial carcinoma	Occurrence of DLT (part 1), ORR (part 2)
NCT04042701 N = 115	Phase I dose escalation (part1) and dose expansion (part 2). Single arm with T-Dxd plus pembrolizumab	HER2-positive BC, HER2-low expressing BC, HER2-expressing NSCLC, and HER2-mutant NSCLC	Occurrence of DLTs (part 1) and ORR (part 2)	Accruing

AE adverse event, BC breast cancer, CT chemotherapy, DLT dose-limiting toxicity, FISH fluorescence in situ hybridization, HER2 human epidermal growth factor receptor 2, HR hormone receptor, IHC immunohistochemistry, IDFS invasive disease-free survival, MBC metastatic breast cancer, NSCLC non-small cell lung cancer, ORR objective response rate, OS overall survival, pCR pathologic complete response, PFS progression-free survival, T-DM1 trastuzumab emtansine, T-Dxd trastuzumab deruxtecan, TPC treatment of physician’s choice

^aNumber of patients that will be included in the arm containing Trastuzumab deruxtecan