DESTINY-Breast03 Phase 3 Study Results
DS8201-A-U105 Study Design
Part 1: Dose Escalation
Key Eligibility Criteria
⚫ HER2-expressing locally
advanced unresectable/
metastatic BC or UC
(centrally confirmed)a
• ECOG PS 0 or 1
.
≥1 measurable lesion
per RECIST v1.1
No prior T-DXd or 1-0
To be eligible for part 1,
patients must meet
additional cohort-specific
criteria of part 2b
T-DXd 3.2 mg/kg
Nivolumab 360 mg
Q3WC
n = 4
Nivolumab 360 mg
Q3WC
n = 3
RDEd
T-DXd 5.4 mg/kg
Part 2: Dose Expansion
Cohort 1: HER2-positive
(IHC 3+ or IHC 2+/ISH+) BC
after T-DM1
n = 29€
Cohort 2: HER2-low
(IHC 1+ or IHC 2+/ISH-) BC
after standard treatment
n = 16
Cohort 3: HER2-high (IHC 3+/2+) UC
after chemotherapy
n = 30
Cohort 4: HER2-low (IHC 1+) UC
after chemotherapy
n = 4
Primary endpoint
Part 1: MTD or RDE
⚫ Part 2: ORR! by ICR
Secondary endpoints
⚫ DOR, DCR, PFS, and
TTR by ICR;
investigator-assessed
ORR and OS
⚫ PK/PD
Safety and tolerability
Exploratory endpoint
⚫ Biomarkers of
resistance/response
DCO: July 22, 2021
Daiichi-Sankyo
BC, breast cancer; DCO, data cutoff; DCR, disease control rate; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; HER2, human epidermal growth factor receptor 2; 1-0,
immuno-oncology; ICR, independent central review; IHC, immunohistochemistry; ISH, in situ hybridization; MTD, maximum tolerated dose; ORR, objective response rate; OS, overall survival; PD-L1, programmed death
ligand 1; PFS, progression-free survival; PK/PD, pharmacokinetics/pharmacodynamics; Q3W, every 3 weeks; RECIST v1.1, Response Evaluation Criteria in Solid Tumours, version 1.1; RDE, recommended dose for
expansion; T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan; TTR, time to response; UC, urothelial carcinoma.
aBy IHC (BC and UC) and ISH (BC) before enrollment. Includes all inclusion criteria listed and cohort descriptions in Part 2. Other inclusion criteria were: cohort 1 patients had prior T-DM1 therapy with documented
progression; cohort 2 patients should have exhausted treatments that could confer any clinically meaningful benefit; cohorts 3 and 4 patients had prior platinum-based combination chemotherapy with documented
progression.
Nivolumab 360 mg Q3W is an approved dose in the United States for certain indications in combination with ipilimumab or fluoropyrimidine- and platinum-containing chemotherapy (Opdivo [nivolumab] prescribing
information) and is currently under investigation in monotherapy oncology studies. The RDE for T-DXd was 5.4 mg/kg. Data from 3 patients treated with the RDE of 5.4 kg/mg in part 1 were pooled with data from cohort
1 for part 2. fORR was based on RECIST v1.1. 9Biomarker data (PD-L1 expression by IHC) were assessed from baseline archival or new tumor tissue biopsies.
ESMO BC 2022 #1620 Oral
61View entire presentation