DESTINY-Breast03 Trial

ENHERTU was approved based on DESTINY-Breast03^1,2

A Phase 3, multicenter, open-label, randomized, head-to-head study to compare the efficacy and safety of ENHERTU vs T-DM1 (ado-trastuzumab emtansine)

In DESTINY-Breast03 (N=524), a head-to-head study of ENHERTU (n=261) vs T-DM1 (n=263), patients received ENHERTU 5.4 mg/kg IV Q3W

Primary endpoint

PFS (BICR)^a

Secondary endpoints

OS
Confirmed ORR^b (BICR)^a

Select exclusion criteria

History of ILD/pneumonitis requiring steroids or ILD/pneumonitis at screening
Clinically significant cardiac disease
Untreated and symptomatic brain metastases^c
ECOG performance status >1
Prior treatment with an anti-HER2 ADC in the metastatic setting

^aBased on RECIST v1.1.¹

^bAnalysis was performed based on the patients with measurable disease assessed by BICR at baseline (n=248 patients randomized to receive ENHERTU; n=241 for T-DM1).¹

^cSubjects with treated brain metastases that were no longer symptomatic and who did not require treatment with corticosteroids or anticonvulsants were included in the study if they had recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.³

Patient demographics were balanced between treatment arms

Select baseline patient demographics and disease characteristics^2,3		ENHERTU (n=261)	T-DM1 (n=263)
Median age		54 (range: 27-83)	54 (range: 20-83)
Female		96.6%	99.6%
White		27%	27%
Asian		58%	62%
Black or African American		4%	3%
Other race		10%	8%
ECOG performance status at baseline	0	59%	67%
ECOG performance status at baseline	1	41%	33%
Hormone receptor status		Positive: 50%	Positive: 51%
Previous systemic cancer therapy^d	Trastuzumab + taxane	99.6%	99.6%
Previous systemic cancer therapy^d	Pertuzumab	62.1%	60.1%
Prior lines of therapy in the metastatic setting (includes rapid progressors as 1 line of treatments)^e	0-1	50.6%	47.9%
	2+	49.4%	52%

Select baseline patient demographics and disease characteristics^2,3	ENHERTU (n=261)	T-DM1 (n=263)
Median age	54 (range: 27-83)	54 (range: 20-83)
Female	96.6%	99.6%
White	27%	27%
Asian	58%	62%
Black or African American	4%	3%
Other race	10%	8%
ECOG performance status at baseline
0	59%	67%
1	41%	33%
Hormone receptor status	Positive: 50%	Positive: 51%
Previous systemic cancer therapy^d
Trastuzumab + taxane	99.6%	99.6%
Pertuzumab	62.1%	60.1%
Prior lines of therapy in the metastatic setting (includes rapid progressors as 1 line of treatments)^e
0-1	50.6%	47.9%
2+	49.4%	52%

^dAll patients received at least 1 prior cancer therapy. One patient with prior T-DM1 treatment was enrolled in error in the ENHERTU arm.

^eRapid progressors defined as progression within 6 months of (neo)adjuvant therapy or 12 months if regimen contained pertuzumab. Line of therapy does not include endocrine therapy.

Sites of metastases³	ENHERTU (n=261)	T-DM1 (n=263)
Presence of visceral disease	71%	70%
Lung metastases	43%	49%
Liver metastases	35%	29%
Brain metastases^f	24%	20%

Sites of metastases³	ENHERTU (n=261)
Presence of visceral disease	71%
Lung metastases	43%
Liver metastases	35%
Brain metastases^f	24%

Sites of metastases³	T-DM1 (n=263)
Presence of visceral disease	70%
Lung metastases	49%
Liver metastases	29%
Brain metastases^f	20%

^fIncluded all patients with a reported history of CNS metastases at baseline. Subjects with treated brain metastases that were no longer symptomatic and who did not require treatment with corticosteroids or anticonvulsants were included in the study if they had recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.³