第一三共与阿斯利康公布Enhertu III期DESTINY-Lung04结果：一线治疗HER2突变晚期NSCLC中位PFS达14.3个月

Enhertu® Demonstrated a Median Progression-Free Survival of 14.3 Months
as First-Line Therapy in Patients with HER2 Mutant Advanced Non-Small
Cell Lung Cancer in DESTINY-Lung04 Phase 3 Trial

• Represents a six-month improvement in median progression- free survival versus p embrolizumab plus
chemotherapy
• Daiichi Sankyo and AstraZeneca’s Enhertu is the first HER2 directed medicine to delay disease progression
over standard of care in a phase 3 trial in this setting

Tokyo – ( September 14, 2026) – Positive results from the DESTINY- Lung04 phase 3 trial showed Enhertu ®
(trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in
progression- free survival (PFS) versus global standard of care (platinum- pemetrexed doublet chemotherapy plus
pembrolizumab) as a first-line treatment of patients with unresectable, locally advanced or metastatic HER2
mutant non- squamous non- small cell lung cancer (NSCLC). Results were presented today (#PL03.08) in
Presidential Symposium 2 at the IASLC 2026 World Conference on Lung Cancer hosted by the International
Association for the Study of Lung Cancer (#WCLC26).

Enhertu is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi
Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca
(LSE/STO/NYSE: AZN).

In the primary endpoint analysis, Enhertu monotherapy significantly reduced the risk of disease progression or
death by 37 .0% versus pembrolizumab plus chemotherapy (hazard ratio [HR] = 0.63; 95% confidence interval [CI]:
0.50- 0.79; p<0.0001). Median PFS was 14.3 months (95% CI: 12.4- 16.5) with Enhertucompared to 8.3 months
(95% CI: 7.0- 9.9) for pembrolizumab plus chemotherapy as assessed by blinded independent central review
(BICR). A favorable PFS trend was seen for Enhertu across key subgroups, including the prespecified stratification
factors of presence or history of brain metastases, smoking status, HER2 mutation status (exon 19 or exon 20), de
novoor recurrent disease and presence of liver metastases.

Objective response rate (ORR) with Enhertu was 70.0% (95% CI: 63.6- 75.9) versus 44.5% (95% CI: 37.9- 51.2)
with pembrolizumab plus chemotherapy. Median duration of response (DOR) for Enhertuwas 13.4 months (95%
CI: 10.4- 17.2) and9.7 months (95% CI: 7.0- 11.1) with pembrolizumab plus chemotherapy. Median PFS2 (time
from treatment start to second tumor progression or death from any cause) with Enhertu was 22.7 months (95%
CI: 20.3- 26.3) compared to 17.3 months (95% CI: 15.6- 21.8) with pembrolizumab plus chemotherapy.

At the time of analysis, the overall survival (OS) data were 46.9% mature and no formal hypothesis testing was
performed. While there was no observed benefit in OS, varied and imbalancedsubsequent therapy patterns
between arms may limit the interpretation of this result. Imbalances include greater use of HER2 directed therapies
in the pembrolizumab plus chemotherapy arm versus the Enhertu arm (48.0% versus 23.3%), and limited use of
subsequent immunotherapy plus chemotherapy in the Enhertu arm (23.8%).

“ HER2 mutant non- small cell lung cancer is an aggressive disease with limited responses to current first-line
standard of care and many patients experienc e disease progressionwithin a year of starting treatment,” said Julia
Rotow, MD, Assistant Professor of Medicine, Dana- Farber Cancer Institute and Lead Investigator of the DESTINY-
Lung04 Trial. “ With 70percent of patients responding and a median progression- free survival of 14.3 months,
trastuzumab deruxtecan has the potential to become an important new first-line treatment option for these
patients.”

The safety profile of Enhertu observed in DESTINY-Lung04 was generally consistent with its known profile with no
new safety signals identified. Grade 3 or higher treatment related adverse events (TRAE) occurred in 34.1% of
patients treated with Enhertu. The most common grade 3 or higher TR AE occurring in 5% or more of patients
treated with Enhertuwas neutropenia (11.1%). Interstitial lung disease (ILD) or pneumonitis events occurred in
20.8% of patients treated with Enhertu as determined by an independent adjudication committee. The majority of
ILD or pneumonitis events were low grade (grade 1 [n=7; 3.1%] or grade 2 [n= 30; 13.3%]). There were five (2.2%)
grade 3, one (0.4%) grade 4 and four (1.8%) grade 5 ILD events in the Enhertu arm.

“Enhertu was the first HER2directed medicine and antibody drug conjugate approved for patients with HER2
mutant non- small cell lung cancer and has become a second- line standard of care treatment,” said John Tsai, MD,
Global Head of R&D, Daiichi Sankyo. “The progression- free survival benefit of six months and strong response
rates seen in DESTINY -Lung04 reinforce the importance of targeting HER2 directly in these patients and support
the potential of Enhertu in the first -line setting where delaying disease progression for as long as possible is a
critical goal.”

“ DESTINY- Lung04 is the first phase 3trial to demonstratesuperior progression- free survival versus the global first -
line standard of care in patients with HER2 mutant advanced non- small cell lung cancer,” said Susan Galbraith,
MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “These results add to the
growing body of evidence supporting Enhertu as an important treatment for patients with HER2 alterations and
underscore its potential role at the time of metastatic diagnosis, when treatment has the greatest opportunity to
improve outcomes.”

Patients in the DESTINY-Lung04trial received prior radiotherapy, chemotherapy, immunotherapy or targeted
therapy for early-stage disease. Approximately three- quarters (75.8%) of the patients in the Enhertu arm had de
novo disease, meaning the lung cancer was first diagnosed in the metastatic setting, and nearly one- quarter
(22.9%) had brain metastases at baseline. Median duration of follow-up was 21.6 months with patients receiving
Enhertu and 20.4 months with patients receiving pembrolizumab plus chemotherapy. As of the data cut-off date of
June 9, 2026 , 50patients remained on study treatment with 40 patients still receiving Enhertu and 10 patients
receiving pembrolizumab plus chemotherapy.

Summary of DESTINY-Lung04 Primary Results
Efficacy Measure Enhertu (5.4 mg/kg) Pembrolizumab plus
(n=227) Chemotherapy
(n=227)
Median PFSi, (months) (95% CI) 14.3 months (12.4-16.5) 8.3 months (7.0-9.9)
HR = 0.63 (0.50-0.79); p<0.0001
ORRii (%) (95% CI) 70.0% (63.6-75.9) 44.5% (37.9-51.2)
CRi,iii, % (n) 1.8% (4) 1.8% (4)
PRi,iii, % (n) 68.3% (155) 42.7% (97)
SDi,iii, % (n) 26.9% (61) 43.2% (98)
Median DORi, (months) (95% CI) 13.4 months (10.4-17.2) 9.7 months (7.0-11.1)
Median PFS2iv, (months) (95% CI) 22.7 months (20.3-26.3) 17.3 months (15.6-21.8)
HR = 0.80 (0.62-1.02)
Median OSv, (months) (95% CI) 29.3 months (26.2-33.4) 33.1 months (27.7-40.7)
HR = 1.15 (0.88-1.52)
CI, confidence interval; CR, complete response; DOR, duration of response; ORR, objective response rate; OS, overall survival; PFS,
progression- free survival; PR, partial response; SD, stable disease
i Assessed by BICR
ii ORR is (CR + PR)
iii Includes unconfirmed responses
iv Assessed by investigator
v At DCO, overall data maturity for OS was 46.9%. No formal hypothesis testing was performed at this interim analysis; formal hypothesis
testing will be performed at the second interim analysis and final analysis

About DESTINY-Lung04
DESTINY- Lung04 is a global, randomized, open- label, phase 3 trial evaluating the efficacy and safety of Enhertu
(5.4 mg/kg) compared to standard of care (platinum- pemetrexed doublet chemotherapy in combination with
pembrolizumab) in patients with unresectable, locally advanced or metastatic, non-squamous NSCLC harboring
a HER2 exon 19 or 20 mutation.

Patients were randomized 1:1 to receive either Enhertu or standard of care. Randomization was stratified by
smoking history and presence or history of brain metastasis. The primary endpoint of DESTINY -Lung04 is PFS as
assessed by BICR. Secondary endpoints include OS, investigator-assessed PFS, ORR and DOR as assessed by
BICR and investigator, investigator-assessed PFS2, pharmacokinetics and safety.

DESTINY- Lung04 enrolled 454 patients across multiple sites in Asia, Europe and North America. For more
information about the trial, visit ClinicalTrials.gov .

About HER2 Mutant NSCLC
Lung cancer is the most commonly diagnosed cancer globally and remains the leading cause of cancer-related
death. 1 In 2024 , approximately 2.6 million new lung cancer cases were reported worldwide , with an estimated 1.8
million deaths.1 NSCLC is the most common type of lung cancer, accounting for approximately 85% of cases.2
Prognosis is particularly poor for patients with metastatic NSCLC as only approximately 10% will live beyond five
years after diagnosis. 3, 4, 5

HER2 is a tyrosine kinase receptor protein involved in cell growth and differentiation and expressed on the surface
of multiple tumor types. HER2 mutations have been identified in NSCLC as distinct molecular targets and have
been reported in approximately 2% to 4% of patients with non- squamous NSCLC. 6, 7, 8, 9 These HER2 mutations are
predominantly seen in younger women and people with no smoking history and have been independently
associated with cancer cell growth and poor prognosis, with an increased incidence of brain
metastases.6, 10, 11, 12, 13, 14

The current global standard of care in the first-line metastatic setting of patients with HER2 mutant NSCLC has
been a combination of immunotherapy and doublet platinum-based chemotherapy. 15, 16, 17 Response rates with this
treatment regimen have been limited and many patients experience disease progression, underscoring the need
for additional treatment options. 18

About Enhertu
Enhertu (trastuzumab deruxtecan; fam- trastuzumab deruxtecan- nxki in the U.S. only) is a HER2 directed ADC.
Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, Enhertu is the lead ADC in the oncology
portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. Enhertu
consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan
derivative, DXd) via tetrapeptide- based cleavable linkers.

Enhertu (5.4 mg/kg) followed by THP is approved in Brazil, China, India, Singapore, Taiwan and the U.S. as a
neoadjuvant treatment for adult patients with HER2 positive (IHC 3+ or ISH+) stage 2 or stage 3 breast cancer
based on the results from the DESTINY- Breast11 trial. Continued approval in China for this indication may be
contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (5.4 mg/kg) is approved in Brazil, Canada, India and the U.S. for the adjuvant treatment of adult patients
with HER2 positive breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or
without pertuzumab) and taxane- based treatment based on the DESTINY- Breast05 trial.

Enhertu (5.4 mg/kg) in combination with pertuzumab is approved in more than 40 countries/regions worldwide as a
first-line treatment for adult patients with unresectable or metastatic HER2 positive (IHC 3+ or ISH+) breast cancer,
as determined by a locally or regionally approved test, based on the results from the DESTINY- Breast09 trial.

Enhertu (5.4 mg/kg) is approved in more than 100 countries/regions worldwide for the treatment of adult patients
with unresectable or metastatic HER2 positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-
HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have
developed disease recurrence during or within six months of completing therapy based on the results from the
DESTINY- Breast03 trial.

Enhertu (5.4 mg/kg) is approved in more than 75 countries/regions worldwide for the treatment of adult patients
with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ ISH-) or HER2
ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that
have progressed on one or more endocrine therapies in the metastatic setting based on the results from the
DESTINY- Breast06 trial.

Enhertu (5.4 mg/kg) is approved in more than 100 countries/regions worldwide for the treatment of adult patients
with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior
systemic therapy in the metastatic setting or developed disease recurrence during or within six months of
completing adjuvant chemotherapy based on the results from the DESTINY- Breast04 trial.

Enhertu (5.4 mg/kg) is approved in more than 80 countries/regions worldwide for the treatment of adult patients
with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a
locally or regionally approved test, and who have received a prior systemic therapy based on the results from the
DESTINY- Lung02 and/or DESTINY- Lung05 trials. Continued approval in China and the U.S. for this indication may
be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4 mg/kg) is approved in more than 90 countries/regions worldwide for the treatment of adult patients
with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction
(GEJ) adenocarcinoma who have received a prior trastuzumab- based regimen based on the results from the
DESTINY- Gastric01, DESTINY- Gastric02 and/or DESTINY- Gastric04 trials.

Enhertu (5.4 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients
with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment
and have no satisfactory alternative treatment options based on efficacy results from the DESTINY- PanTumor02,
DESTINY- Lung01, DESTINY- CRC02 and/or HERALD trials. Continued approval in the U.S. for this indication may
be contingent upon verification and description of clinical benefit in a confirmatory trial.

About the Enhertu Clinical Development Program
A comprehensive global clinical development program is underway evaluating the efficacy and safety of Enhertu
as a monotherapy or in combination or sequentially with other cancer medicines across multiple HER2 targetable
cancers.

About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize Enhertu
in March 2019 and Datroway® in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for
each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway.

Enhertu U.S. Indications and Important Safety Information
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for:
• HER2-Positive Early Breast Cancer
− As neoadjuvant treatment of adult patients with HER2- positive (IHC 3+ or ISH+) Stage II or III breast
cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab
(THP)
− As monotherapy in adult patients with HER2- positive (IHC 3+ or ISH+) breast cancer who have residual
invasive disease after neoadjuvant HER2- targeted treatment

• HER2-Positive Metastatic Breast Cancer
− In combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic
HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test
− As monotherapy for the treatment of adult patients with unresectable or metastatic HER2- positive (IHC 3+
or ISH+) breast cancer who have received a prior anti-HER2-based regimen either in the metastatic
setting, or, in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within
six months of completing therapy

• HER2-Low and HER2- Ultralow Metastatic Breast Cancer
− As monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor
(HR)-positive, HER2- low (IHC 1+ or IHC 2+/ISH- ) or HER2-ultralow (IHC 0 with membrane staining) breast
cancer, as determined by an FDA-authorized test, that has progressed on one or more endocrine
therapies in the metastatic setting
− As monotherapy for the treatment of adult patients with unresectable or metastatic HER2- low (IHC 1+ or
IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test, who have received a prior
chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of
completing adjuvant chemotherapy

• HER2-Mutant Unresectable or Metastatic Non- Small Cell Lung Cancer (NSCLC)
− As monotherapy for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors
have activating HER2 (ERBB2) mutations, as detected by an FDA-authorized test, and who have received
a prior systemic therapy

This indication is approved under accelerated approval based on objective response rate and duration of
response. Continued approval for this indication may be contingent upon verification and description of
clinical benefit in a confirmatory trial.

• HER2-Positive Locally Advanced or Metastatic Gastric Cancer
− As monotherapy for the treatment of adult patients with locally advanced or metastatic HER2- positive (IHC
3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have
received a prior trastuzumab- based regimen

• HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors
− As monotherapy for the treatment of adult patients with unresectable or metastatic HER2- positive (IHC 3+)
solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment
options

ImportantSafety Information

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY
• Interstitial lung disease (ILD) and pneumonitis, including severe, life -threatening, and fatal cases, have
been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including
cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue
ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to
immediately report symptoms.
• Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks
and the need for effective contraception.

Contraindications
None.

Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life- threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated
with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with
moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or
worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence
of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist.
For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in
≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level.
Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or
equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly
initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day
prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

HER2-Positive, HER2-Low, and HER2- Ultralow Breast Cancer, HER2- Mutant NSCLC, and Solid Tumors
(Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was
5.5months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients
treated with ENHERTU.

ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), ILD occurred in 12% of
patients. Median time to first onset was 8.0 months (range: 0.6 to 33.8). Fatal outcomes due to ILD and/or
pneumonitis occurred in 0.5% of patients treated with ENHERTU in combination with pertuzumab.

ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, ILD occurred in 4.4% of
patients. Median time to first onset was 2.7 months (range: 1.1 to 6.0). Fatal outcomes due to ILD and/or
pneumonitis occurred in 1 patient (0.3%) treated with ENHERTU followed by THP.

Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete
blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3
neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2
or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to
Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C

or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose
by 1 level.

HER2-Positive, HER2-Low, and HER2- Ultralow Breast Cancer, HER2- Mutant NSCLC, and Solid Tumors
(Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients.
Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil
count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1% of patients.

ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), decreased neutrophil count
occurred in 79% of patients. Median time to first onset was 22 days (range: 5 to 994). Twenty-nine percent had
Grade 3 or 4 decreased neutrophil count. Febrile neutropenia was reported in 2.6% of patients.

ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, a decrease in neutrophil
count was reported in 58% of patients. Seventeen percent had Grade 3 or 4 decreased neutrophil count. Median
time to first onset of decreased neutrophil count was 42 days (range: 11 to 165). Febrile neutropenia was reported
in 0.9% of patients.

HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2- positive gastric or GEJ adenocarcinoma treated with
ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had
Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days
(range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular
dysfunction (LVD) has been observed with anti-HER2 therapies, including ENHERTU. Assess left ventricular
ejection fraction (LVEF) prior to initiation of ENHERTU and at regular intervals during treatment as clinically
indicated. Manage LVD through treatment interruption. When LVEF is >45% and absolute decrease from baseline
is 10-20%, continue treatment with ENHERTU. When LVEF is 40- 45% and absolute decrease from baseline is
<10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40- 45%
and absolute decrease from baseline is 10- 20%, interrupt ENHERTU and repeat LVEF assessment within 3
weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF
recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40%
or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If
LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU.
Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with
ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50%
prior to initiation of treatment.

ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), LVEF decrease was
reported in 11% of patients, of which 2.1% were Grade 3 or 4.

ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, LVD was reported in 1.3% of
patients, of which 0.3% were Grade 3.

HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2- positive gastric or GEJ adenocarcinoma treated with
ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography,
8% were found to have asymptomatic Grade 2 decrease in LVEF.

Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to
a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise
females of reproductive potential to use effective contraception during treatment and for 7 months after the last
dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective
contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.

Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less,
then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to
Grade 1 or less, then reduce dose by 1 level.

Radiotherapy-Related Pneumonitis and Skin Injury in the Post- Neoadjuvant Early Breast Cancer Setting
Among patients receiving sequential or concurrent adjuvant radiotherapy in DESTINY-Breast05, radiation
pneumonitis occurred in 31% of patients receiving ENHERTU 5.4 mg/kg (N=757) and 31% of patients receiving
ado- trastuzumab emtansine (T-DM1) 3.6 mg/kg (N=750), as reported by the investigator. All cases of patients
receiving ENHERTU and adjuvant radiotherapy (ART) were either Grade 1 (27%) or Grade 2 (4.9%). A higher
incidence of radiation pneumonitis was reported for patients who received sequential vs concurrent ART: 34% with
sequential ART and 29% with concurrent ART. For patients treated with ENHERTU, median time to onset of first
event of radiation pneumonitis was 4.1 months (range: 1.3 to 11.6). Among 39% of patients with recovery of first
event of radiation pneumonitis, median duration was 3.5 months (range: <0.1 to 33.8). Among patients receiving
ART and ENHERTU, radiation skin injury occurred in 20% of all patients, of which 1.6% were Grade 3 and none
were Grade 4. For Grade 1 (asymptomatic) radiotherapy -related pneumonitis, continue treatment with ENHERTU.
For Grade 2 (symptomatic), interrupt ENHERTU until recovered to baseline or Grade ≤1. For Grade ≥3
(symptomatic, severe, or life- threatening), permanently discontinue ENHERTU. Manage Grade ≥2 per local
institutional guidelines.

Adverse Reactions
HER2-Positive, HER2-Low, and HER2- Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors
(Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233
patients in Study DS8201-A- J101 (NCT02564900), DESTINY- Breast01, DESTINY-Breast02, DESTINY-Breast03,
DESTINY- Breast04, DESTINY- Breast06, DESTINY-Lung01, DESTINY- Lung02, DESTINY-CRC02, and DESTINY-
PanTumor02. Among these patients, 67% were exposed for >6 months and 39% were exposed for >1 year. In this
pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were
decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count
(65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate
aminotransferase (46%), increased alanine aminotransferase (43%), increased blood alkaline phosphatase (39%),
vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%),
diarrhea (30%), and musculoskeletal pain (24%).

ENHERTU in Combination with Pertuzumab
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg in combination with pertuzumab
intravenously every 3 weeks in 431 patients in DESTINY-Breast07 (n=50), and DESTINY-Breast09 (n=381).
Among these patients, 86% were exposed for >6 months and 73% were exposed for >1 year. In this pooled safety
population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white
blood cell count (86%), decreased hemoglobin (80%), decreased neutrophil count (79%), nausea (74%), increased
alanine aminotransferase (65%), diarrhea (64%), increased aspartate aminotransferase (63%), decreased
lymphocyte count (61%), decreased platelet count (55%), increased blood alkaline phosphatase (54%), decreased
blood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (32%),

constipation (31%), decreased appetite (31%), decreased weight (28%), musculoskeletal pain (23%), increased
blood bilirubin (23%) and abdominal pain (22%).

HER2-Positive Early Breast Cancer
DESTINY- Breast11
The safety of ENHERTU followed by THP was evaluated in 320 patients with HER2- positive (IHC 3+ or ISH+)
early breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11.
ENHERTU was administered by intravenous infusion once every three weeks for 4 cycles followed by THP for 4
cycles. The median duration of treatment was 5.6 months (range: 0.7 to 9.1) for patients who received ENHERTU
followed by THP.

Serious adverse reactions occurred in 11% of patients receiving ENHERTU followed by THP, including COVID-19
(0.9%) and ILD/pneumonitis (0.6%). Fatal adverse reactions occurred in 0.6% of patients, including
ILD/pneumonitis and death not otherwise specified (1 patient each).

In patients treated with ENHERTU followed by THP, the permanent discontinuation of ENHERTU due to adverse
reactions occurred in 1.3%, of which ILD/pneumonitis accounted for 0.6%. Dose interruptions of ENHERTU due to
adverse reactions occurred in 11% of patients. The most frequent adverse reactions (>2%) associated with dose
interruption were decreased neutrophil count and COVID-19. Dose reductions of ENHERTU occurred in 2.5% of
patients treated with ENHERTU.

The most common (≥20%) adverse reactions in patients treated with ENHERTU followed by THP, including
laboratory abnormalities, were decreased hemoglobin (83%), increased alanine aminotransferase (79%),
increased aspartate aminotransferase (74%), decreased white blood cell count (67%), nausea (65%), peripheral
neuropathy (59%), diarrhea (59%), decreased neutrophil count (58%), alopecia (48%), fatigue (41%), decreased
lymphocyte count (40%), rash (31%), musculoskeletal pain (30%), decreased blood potassium (29%), constipation
(29%), vomiting (29%), stomatitis (23%), and decreased appetite (20%).

DESTINY- Breast05
The safety of ENHERTU was evaluated in 806 patients with HER2- positive breast cancer with residual invasive
disease following neoadjuvant HER2- targeted therapy who then received at least one dose of ENHERTU 5.4
mg/kg. ENHERTU was administered by intravenous infusion once every three weeks for 14 cycles. The median
duration of treatment was 10 months (range: 0.7 to 16) for patients who received ENHERTU.

Serious adverse reactions occurred in 17% of patients receiving ENHERTU. Serious adverse reactions in ≥1% of
patients who received ENHERTU were ILD/pneumonitis, radiation pneumonitis, pneumonia, and platelet count
decreased. Fatal adverse reactions occurred in 0.4% of patients including ILD/pneumonitis (2 patients) and
respiratory tract infection (1 patient).

Permanent discontinuation of ENHERTU due to an adverse reaction occurred in 18% of patients. The adverse
reaction which resulted in permanent discontinuation of ENHERTU >2% included ILD/pneumonitis. Dose
interruptions of ENHERTU due to an adverse reaction occurred in 50% of patients. Adverse reactions which
required dosage interruptions in >2% included radiation pneumonitis, neutrophil count decreased, COVID-19,
white blood cell count decreased, ILD/pneumonitis, platelet count decreased, upper respiratory tract infection,
fatigue, cough, and pyrexia. Dose reductions of ENHERTU due to an adverse reaction occurred in 26% of
patients. Adverse reactions which required dose reductions in >2% of patients included nausea, fatigue, platelet
count decreased, and neutrophil count decreased.

The most common (≥20%) adverse reactions, including laboratory abnormalities, in patients receiving ENHERTU
were decreased white blood cell count (80%), decreased lymphocyte count (72%), decreased neutrophil count
(72%), nausea (71%), decreased hemoglobin (61%), increased aspartate aminotransferase (60%), fatigue (54%),
increased alanine aminotransferase (53%), decreased platelet count (46%), increased blood alkaline phosphatase
(39%), constipation (32%), vomiting (31%), decreased blood potassium (27%), diarrhea (23%), musculoskeletal
pain (23%), and decreased appetite (20%).

HER2-Positive Metastatic Breast Cancer
DESTINY- Breast09
The safety of ENHERTU 5.4 mg/kg in combination with pertuzumab was evaluated in DESTINY-Breast09, a
randomized, three- arm, multicenter study including 763 patients with HER2- positive (IHC 3+ or ISH+) unresectable
or metastatic breast cancer. Three hundred eighty-one patients received ENHERTU in combination with
pertuzumab and 382 patients received THP (taxane [docetaxel or paclitaxel], trastuzumab, and pertuzumab).
Among patients who received ENHERTU in combination with pertuzumab, the median duration of treatment was
22 months (range: 0.3 months to 44.5 months).

Serious adverse reactions occurred in 27% of patients receiving ENHERTU in combination with pertuzumab.
Serious adverse reactions in >1% of patients were diarrhea, pneumonia, febrile neutropenia, hypokalemia,
vomiting, ILD, pulmonary embolism, and sepsis. Fatalities due to adverse reactions occurred in 3.4% of patients
including pneumonia (n=3), ILD (n=2), sepsis (n=2), pulmonary embolism, septic shock, acute kidney injury,
dyspnea, febrile neutropenia, and intestinal ischemia (1 patient each).

ENHERTU was discontinued for adverse reactions in 21% of patients. The most frequent adverse reaction (>2%)
associated with permanent discontinuation was ILD/pneumonitis (6%). Dose interruptions due to adverse reactions
occurred in 69% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were
COVID-19, neutropenia, upper respiratory tract infection, fatigue, anemia, hypokalemia, ILD/pneumonitis,
thrombocytopenia, pneumonia, diarrhea, transaminase increased, leukopenia, cough, pyrexia, decreased appetite,
and blood bilirubin increased. Dose reductions occurred in 46% of patients treated with ENHERTU in combination
with pertuzumab. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue,
neutropenia, nausea, diarrhea, ILD/pneumonitis, thrombocytopenia, vomiting, transaminases increased,
decreased weight, febrile neutropenia, and hypokalemia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell
count (87%), decreased hemoglobin (80%), decreased neutrophil count (78%), nausea (75%), increased alanine
aminotransferase (66%), diarrhea (64%), increased aspartate aminotransferase (62%), decreased lymphocyte
count (62%), decreased platelet count (56%), increased blood alkaline phosphatase (55%), decreased blood
potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (33%),
constipation (33%), decreased appetite (32%), decreased weight (30%), COVID-19 (28%), musculoskeletal pain
(24%), increased blood bilirubin (23%), and abdominal pain (23%).

DESTINY- Breast03
The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2- positive breast
cancer who received at least 1 dose of ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-
Breast03. The median duration of treatment was 14 months (range: 0.7 to 30) for patients who received
ENHERTU.

Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of
patients who received ENHERTU were vomiting, ILD, pneumonia, pyrexia, and urinary tract infection. Fatalities
due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (1 patient each).

ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose
interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent
adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia,
thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients
treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea,
neutropenia, and fatigue.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased
white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%),
decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%),
decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%),
alopecia (37%), decreased blood potassium (35%), constipation (34%), musculoskeletal pain (31%), diarrhea
(29%), decreased appetite (29%), headache (22%), respiratory infection (22%), abdominal pain (21%), increased
blood bilirubin (20%), and stomatitis (20%).

HER2-Low and HER2- Ultralow Metastatic Breast Cancer
DESTINY- Breast06
The safety of ENHERTU was evaluated in 434 patients with unresectable or metastatic HER2- low (IHC 1+ or IHC
2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who received ENHERTU 5.4 mg/kg
intravenously once every 3 weeks in DESTINY- Breast06. The median duration of treatment was 11 months
(range: 0.4to 39.6) for patients who received ENHERTU.

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of
patients who received ENHERTU were ILD/pneumonitis, COVID-19, febrile neutropenia, and hypokalemia.
Fatalities due to adverse reactions occurred in 2.8% of patients including ILD (0.7%); sepsis (0.5%); and COVID-
19 pneumonia, bacterial meningoencephalitis, neutropenic sepsis, peritonitis, cerebrovascular accident, general
physical health deterioration (0.2% each).

ENHERTU was permanently discontinued in 14% of patients. The most frequent adverse reaction (>2%)
associated with permanent discontinuation was ILD/pneumonitis. Dose interruptions due to adverse reactions
occurred in 48% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with
dose interruption were COVID-19, decreased neutrophil count, anemia, pyrexia, pneumonia, decreased white
blood cell count, and ILD. Dose reductions occurred in 25% of patients treated with ENHERTU. The most frequent
adverse reactions (>2%) associated with dose reduction were nausea, fatigue, decreased platelet count, and
decreased neutrophil count.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell
count (86%), decreased neutrophil count (75%), nausea (70%), decreased hemoglobin (69%), decreased
lymphocyte count (66%), fatigue (53%), decreased platelet count (48%), alopecia (48%), increased alanine
aminotransferase (44%), increased blood alkaline phosphatase (43%), increased aspartate aminotransferase
(41%), decreased blood potassium (35%), diarrhea (34%), vomiting (34%), constipation (32%), decreased appetite
(26%), COVID-19 (26%), and musculoskeletal pain (24%).

DESTINY- Breast04
The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2- low (IHC 1+ or IHC
2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-
Breast04. The median duration of treatment was 8 m onths (range: 0.2to 33) for patients who received ENHERTU.

Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of
patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis,
anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions
occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis,
disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural
effusion, and respiratory failure (1 patient each).

ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose
interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent
adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-
19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of
patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were
fatigue, nausea, thrombocytopenia, and neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased
white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased
lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%),
increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%),
increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea
(27%), and decreased blood potassium (25%).

HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)
DESTINY- Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for
the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity
observed with the higher dose in patients with NSCLC, including ILD/pneumonitis.

The safety of ENHERTU was evaluated in 101 patients with HER2- mutant unresectable or metastatic NSCLC who
received ENHERTU 5.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable
toxicity in DESTINY-Lung02. The median duration of treatment was 8 months (range: 0.7 to 28) for patients who
received ENHERTU.

Serious adverse reactions occurred in 40% of patients receiving ENHERTU. Serious adverse reactions in >1% of
patients who received ENHERTU were ILD/pneumonitis, pleural effusion, thrombocytopenia, dyspnea, nausea,
pneumonia, vomiting, myocarditis, pulmonary embolism, and increased troponin I. Fatalities due to adverse
reactions occurred in 3% of patients including ILD/pneumonitis, cerebrovascular accident, and pneumococcal
sepsis (1 patient each).

ENHERTU was permanently discontinued in 17% of patients. Adverse reactions which resulted in permanent
discontinuation of ENHERTU were ILD/pneumonitis, pneumonia, blood bilirubin increased, hypokalemia,
metastases to meninges, and myocarditis. Dose interruptions of ENHERTU due to adverse reactions occurred in
50% of patients. Adverse reactions which required dose interruption (>2%) included neutropenia, COVID-19,
ILD/pneumonitis, fatigue, anemia, and pneumonia. Dose reductions due to an adverse reaction occurred in 20% of
patients. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, fatigue,
and decreased appetite.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin
(68%), nausea (67%), decreased white blood cell count (66%), decreased neutrophil count (59%), decreased
lymphocyte count (56%), increased aspartate aminotransferase (51%), decreased albumin (50%), decreased
platelet count (49%), fatigue (48%), increased alanine aminotransferase (41%), decreased appetite (41%),
constipation (38%), increased alkaline phosphatase (37%), vomiting (32%), decreased blood potassium (29%),
diarrhea (24%), alopecia (22%), and musculoskeletal pain (21%).

HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2- positive gastric
or GEJ adenocarcinoma in DESTINY- Gastric01. Patients intravenously received at least 1 dose of either
ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7)
80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients
who received ENHERTU.

Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions
in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia,
cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of
patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in 1 patient
each (0.8%).

ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions
due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions
(>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue,
thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and decreased blood
potassium. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse
reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile
neutropenia.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin
(75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count
(70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate
aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine
aminotransferase (47%), diarrhea (32%), decreased blood potassium (30%), vomiting (26%), constipation (24%),
increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%).

HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors
The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2- positive (IHC
3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01,

DESTINY- PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3
months (range 0.7 to 30.2).

Serious adverse reactions occurred in 34% of patients receiving ENHERTU. Serious adverse reactions in >1% of
patients who received ENHERTU were sepsis, pneumonia, vomiting, urinary tract infection, abdominal pain,
nausea, pneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney injury, anemia, cellulitis, and
dyspnea. Fatalities due to adverse reactions occurred in 6.3% of patients including ILD/pneumonitis (2.3%),
cardiac arrest (0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in 1 patient each
(0.3%): acute kidney injury, cerebrovascular accident, general physical health deterioration, pneumonia, and
hemorrhagic shock.

ENHERTU was permanently discontinued in 15% of patients, of which ILD/pneumonitis accounted for 10%. Dose
interruptions due to adverse reactions occurred in 48% of patients. The most frequent adverse reactions (>2%)
associated with dose interruption were decreased neutrophil count, anemia, COVID-19, fatigue, decreased white
blood cell count, and ILD/pneumonitis. Dose reductions occurred in 27% of patients treated with ENHERTU. The
most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, decreased neutrophil
count, ILD/pneumonitis, and diarrhea.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell
count (75%), nausea (69%), decreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%),
decreased lymphocyte count (58%), decreased platelet count (51%), increased aspartate aminotransferase (45%),
increased alanine aminotransferase (44%), increased blood alkaline phosphatase (36%), vomiting (35%),
decreased appetite (34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%), constipation (28%),
decreased sodium (22%), stomatitis (20%), and upper respiratory tract infection (20%).

Use in Specific Populations
• Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the
potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a
patient becomes pregnant within 7 months after the last dose of ENHERTU.
• Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed
child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed
child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
• Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of
reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal
harm when administered to a pregnant woman. Advise females of reproductive potential to use effective
contraception during treatment with ENHERTU and for 7 months after the last dose. Males : Advise male
patients with female partners of reproductive potential to use effective contraception during treatment with
ENHERTU and for 4 months after the last dose. Infertility : ENHERTU may impair male reproductive function
and fertility.
• Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
• Geriatric Use: ENHERTU as Monotherapy : Of the 2233 patients treated with ENHERTU 5.4 mg/kg, 28% were
≥65 years and 6% were ≥75 years. No overall differences in efficacy within clinical studies were observed
between patients ≥65 years compared to younger patients. There was a higher incidence of Grade 3- 4
adverse reactions observed in patients aged ≥65 years (56%) as compared to younger patients (49%). Of the
125 patients with HER2- positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with
ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall
differences in efficacy or safety were observed between patients ≥65 years of age compared to younger
patients. ENHERTU in Combination with Pertuzumab: In patients with HER2- positive unresectable or
metastatic breast cancer treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), 17%
were ≥65 years and 3% were ≥75 years. No overall differences in efficacy or safety were observed between
patients ≥65 years compared to younger patients. ENHERTU followed by THP: Of the 320 patients with
HER2-positive early breast cancer treated with ENHERTU 5.4 mg/kg followed by THP, 12% were ≥65 years
and 1.6% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years
compared to younger patients. There was a higher incidence of Grade 3- 4 adverse reactions observed in
patients ≥65 years (38%) as compared to younger patients (30%).
• Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with
moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The

recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr
<30 mL/min).
• Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure,
monitor for increased adverse reactions related to the topoisomerase inhibitor, DXd. The recommended
dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3
times ULN and any AST).

To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1 -877- 437- 7763 or FDA at 1-
800- FDA- 1088 or fda.gov/medwatch.

Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication
Guide.

About the ADC Portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of nine ADCs in clinical development crafted from ADC technology
discovered in- house by Daiichi Sankyo.

The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development where each
ADC is comprised of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an
exatecan derivative, DXd) via tetrapeptide- based cleavable linkers. The DXd ADCs include Enhertu and Datroway,
which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-
DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3- DXd), which are being jointly developed
and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939 and DS3790 are being developed
by Daiichi Sankyo.

Additional ADCs being developed by Daiichi Sankyo include DS3610, which consists of an antibody attached to a
novel payload that acts as an agonist of STING, and DS1025, which consists of a CD25 directed antibody
attached to an immuno- oncology optimized cytotoxic payload.

Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610, DS3790 and DS1025
are investigational medicines that have not been approved for any indication in any country. Safety and efficacy
have not been established.

About Daiichi Sankyo
Daiichi Sankyo (TSE: 4568) is a global healthcare company committed to becoming a trusted healthcare innovator,
transforming the lives of people through its strength in science and technology. The company discovers and
develops new standards of care to address diverse medical needs to fulfill its purpose of contributing to the
enrichment of quality of life around the world. With a strategic focus on oncology, Daiichi Sankyo is advancing an
industry-leading antibody drug conjugate portfolio along with identifying new breakthrough generating technologies
to deliver practice- changing medicines to patients, healthcare professionals and society. For more information,
please visit www.daiichisankyo.com.

MEDIA CONTACTS: INVESTOR RELATIONS CONTACT:
Global: [email protected]
Jennifer Brennan
[email protected]
+1 908 900 3183 (mobile)

Japan:
[email protected]

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