Clinical Results Summary
A clinical study of DS-8201a to learn about its effects on heart activity and how it isabsorbed, distributed and removed from the body in participants with HER2-positivecancer that had spread and/or could not be surgically removed
Protocol number: DS8201-A-J102
Thank You!

Daiichi Sankyo, Inc., the sponsor of this study, would like to thank the participants who
took part in this study for DS-8201a also known Trastuzumab Deruxtecan (T-DXd). Eachparticipant helped to advance medical research for people affected with HER2-positive
breast cancer. Their contribution to medicine and healthcare is greatly appreciated.

Important note: This summary only shows the results of a single study. Other studies may have different
findings. Researchers and health authorities look at the results of many studies to understand which
treatments work and how they work. It takes a lot of people in many studies around the world to advance
medical science and healthcare.
Do not use the results of this study to make health decisions. Please talk to a doctor before changing any
treatment you are taking or if you have any questions about these study results.

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What was the main purpose of this study?
Advanced cancer
A tumor is an abnormal growth of cells in the body that starts in an organ, muscle, or bone. An advanced
cancer usually means one that has spread to other parts of the body. A certain kind of protein called a kinase
helps tumor cells divide and grow. It is believed that by stopping this protein from working, the growth of thetumor cells can be stopped.
Some people with cancer have an increased level of a protein called HER2, which makes their cells grow anddivide too fast. This is called HER2-positive cancer. DS-8201a, also known as trastuzumab deruxtecan or T-DXd,
specifically binds to HER2-expressing cells to inhibit cell growth and cause the death of target tumor cells.
At this time treatment options for HER2-positive cancers are:• surgery• radiation therapy - a treatment that uses radiation to kill cancer cells• endocrine (hormone) therapy - a treatment that stops the growth of cancer cells that use hormones togrow• chemotherapy – a treatment that uses drugs to kill cancer cells or stop them from growing and dividing
Current treatment options do not work in all patients, therefore new methods for treating these cancers areneeded.

In this study, researchers wanted to learn about the effects of DS-8201a on the activity of the heart asmeasured by electrocardiogram (ECG) tests, and how it is processed by the body after multiple doses inparticipants with HER2-positive advanced cancer.

Treatment given in this study

T-DXd / DS-8201aDrug being studied forthe treatment of HER2-positive
advanced and/or refractory cancer
DS8201-A-J102 Clinical Results Summary | 2Main goals of this study
The main question the researchers wanted to answer in this study was:What was the effect of DS-8201a on heart rhythm and activity?

This was measured using an electrocardiogram (ECG) test.

What were the levels of DS-8201a, its breakdown product MAAA-1181a,
and total anti-HER2 antibody in the blood of participants?

*DS-8201a consists of 2 components. One component is deruxtecan. The other is the HER2
targeted antibody called trastuzumab. The 2 components are designed to stay together until DS8201a binds to a cell with the HER2 marker on it. Once DS-8201a binds to a HER2 positive cell, itgets activated. The 2 components then separate and a released topoisomerase I inhibitor (MAAA1181a) kills the HER2 positive cell.

Other goals of this study
Researchers also wanted to answer the following question:

How many participants had side effects during the study?

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How long was this study?
The study was designed so that participants could continue
in it as long as their tumor did not get worse and they did nothave serious side effects, or were asked to be removed fromthe study. An individual participant could have been in thisstudy for 3 Years and 2 months. The study started in
December 2017 and ended in February 2021.

Who was in this study?
This study included 51 female participants from Japan. Participants could take part in this study if they:•••••

had breast cancer with the presence of HER2
protein that came back after standard
treatment, or could not be treated bystandard treatment, or for which no standard
treatment was available
had at least 50% of total blood pumped out
with each heart beat from the left side of theheart
were either fully active or able to walk and dolight work, but unable to do a hard physicalactivity
Had adequate organ function (for exampleliver, kidneys)
were expected to live for at least 3 months

What happened during this study?
This was a Phase 1 study. Phase 1 studies are done to find out how new study treatment works in a small numberof participants. This helps researchers understand what happens to the study treatment in the body, and if there
are any side effects.
This study was “open label”. This means that both the researchers and the participants knew what treatment
was given to which participants.
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51 participants received 6.4 milligram/kilogram (mg/kg) of DS-8201a through a drip over 90 minutes on the firstday of each cycle, for a minimum of 3 cycles until their tumor did not get worse and they did not have serious
side effects, or were asked to be removed from the study. Each cycle lasted 3 weeks.

What were the key results of this study?
Key results from this study are shown for the total group of participants as average results. This summary does
not show the results from each individual participant. An individual participant’s results could be different
from the total group of participants. A full list of the questions the researchers wanted to answer and adetailed presentation of the results can be found on the website listed at the end of this summary.

What was the effect of DS-8201a on heart rhythm and activity?
The heart is a muscle that contracts and relaxes to pump blood around the body. Researchers found that drug
DS-8201a at 6.4 mg/kg dosing was not associated with a meaningful change in heart muscle.

What were the levels of DS-8201a, its breakdown product MAAA-1181a, andtotal anti-HER2 antibody in the blood of participants?
To answer this question, the researchers measured the total levels of DS-8201a, MAAA-1181a and anti-HER2
antibody in the participants’ blood samples during Cycle 1 and Cycle 3.
Researchers found that the levels of DS-8201a, MAAA-1181a, and anti-HER2 antibody in the participants’blood increased from Cycle 1 to Cycle 3.

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The average results of these measurements are presented below. Total levels of DS-8201a and anti-HER2
antibody in the participants’ blood within the dosing period are measured in μg*d/mL, which means
micrograms (millionths of a gram) found in each milliliter of blood over 1 day. MAAA-1181a is measured inng*d/mL, which means nanograms (one thousand millionths of a gram) found in each milliliter of blood over 1day.

Cycle 1

Cycle 3677

905

39427521030

DS-8201a:
Total level during dosing interval (μg*d/mL)

MAAA-1181a
Total level during dosing interval (ng*d/mL)

Anti-HER2 antibody
Total level during dosing interval (μg*d/mL)

What were the other results of this study?
How many participants had side effects during the study?
During this study, all the participants (51 out of 51, 100%) had at least 1 side effect. Detailed information
about side effects reported by participants is presented in the section below: ‘What medical problems did thestudy participants have ?’What medical problems did the study participants have?
Side effects are medical problems (such as a feeling tired) that happened during the study which the study
doctor thought could be related to the study treatment. This section provides a summary of such side effects.
The website listed at the end of this summary has more information about the medical problems that
happened in this study.
Side effects are considered serious if they cause death, are life-threatening, cause lasting problems, or require
hospitalization. Some participants stop study treatment because of side effects.

How many participants had serious side effects?
In this study, 1 out of 51 participants (2%) had a serious side effect of nausea.
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No participants taking DS-8201a died during this study.

How many people had the most common side effects?
In this study, side effects were monitored for 51 participants given DS-8201a. All participants who were givenDS-8201a reported at least 1 side effect.
The most common side effects, which happened in at least 25% of participants in any group are presentedbelow.
Side Effects

DS-8201a (6.4 mg/kg)
Out of 51 Participants

Decrease in red blood cells count a

57% (29 participants)

Decrease in appetite

31% (16 participants)

Nausea82% (42 participants)

Vomiting

39% (20 participants)

Inflammation of mouth and lips

31% (16 participants)

Diarrhea

28% (14 participants)

Constipation

26% (13 participants)

Bald patches on scalp

41% (21 participants)

Decrease in neutrophil count b

71% (36 participants)

White blood cell count decreased c

61% (31 participants)

Platelet count decreased d

39% (20 participants)

Lymphocyte count decreased e

26% (13 participants)

a red blood cells carry oxygen around the bodyb

neutrophils are white blood cells that help protect from infection
white blood cells help protect your body from infection
dplatelets are a type of blood cell that helps in preventing / stopping bleedingelymphocytes are white blood cells, that protect from infectioncDS8201-A-J102 Clinical Results Summary | 7

How many participants had to stop treatment because of side effects?
28% (14 out of 51) of participants given DS-8201a had stopped treatment early because of side effects. The
most common side effects that led to participants stopping study treatment were heart problems, multiple
lung infection, and pneumonia.

How was this study useful for patients and researchers?
This study helped researchers learn about the effects of DS-8201a on the heart rhythm and activity inparticipants with HER2-positive advanced cancer.
This summary only shows the results of a single study. Other studies may have different findings. Please talk toa doctor before changing any treatment you are taking or if you have any questions about these study results.

Where can I learn more about this study?
You can find more information about this study on the following website:www.clinicaltrials.gov: Use the NCT identifier NCT03366428 in the search field.
Please remember that the results on this website may be presented in a different way. If you were a study
participant and have questions about the results of this study, please speak with the doctor or staff at your study
site.
Full study title:
Phase 1, Multicenter, Open-label, Multiple-DoseStudy of DS-8201a to Assess the Effect on theQT Interval and Pharmacokinetics in Subjects withHER2-expressing Metastatic and/or Unresectable
Breast Cancer

Sponsor: Daiichi Sankyo, Inc.
Sponsor contact information:
211 Mount Airy Road, Basking Ridge, NJ 07920
Email: CTRInfo@dsi.com
Phone number: 1-908-992-6640
Date of this summary: 18 August 2022

This summary was prepared by Syneos Health®.

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