Clinical Results Summary
A clinical study to learn about the effects of DS-8201a in womenwith HER2-positive breast cancer previously treated with T-DM1
that has spread and/ or cannot be surgically removed
Protocol number: DS8201-A-U201

Thank You!

Daiichi Sankyo, Inc., the sponsor of this study, would like to thank the participants who
took part in this study for trastuzumab deruxtecan, also known DS-8201a or T-DXd. Eachparticipant helped to advance medical research for women 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.

What was the main purpose of this study?
Metastatic breast cancer

Researchers were looking for a better way to treat people with unresectable and/or metastatic breast cancer.
Breast cancer starts in the cells of the breasts, and is more common in women than men. These cells divide
more rapidly than the normal cells, forming a lump or mass. “Metastatic” means that cancer has spread toother parts of the body, and “unresectable” means that cancer cannot be completely removed throughsurgery. Symptoms of metastatic breast cancer include swelling in the breast, redness of the skin near thebreast area, weakness in any part of the body, difficulty in breathing, and chest pain.
At this time treatment options for breast cancer are surgery, radiation therapy, endocrine (hormone) therapy
and chemotherapy. Radiation therapy is a type of cancer treatment that uses radiation to kill cancer cells.
Hormone therapy is a cancer treatment that stops the growth of cancer that uses hormones to grow.
Chemotherapy uses medicine 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 breast cancer are needed.
Some people with breast cancer have an increased level of a protein called HER2, which makes their cells growand divide too fast. This is called HER2-positive breast cancer.
DS-8201a, also known as trastuzumab deruxtecan or (as used from this point) T-DXd, specifically binds to
HER2-expressing cells to inhibit the cell growth and cause the death of target tumor cells.
In this study, researchers wanted to learn about the effects of T-DXd in women with HER2-positive breast
cancer who were previously treated with T-DM1 (also known as trastuzumab emtansine).

Treatment given in this study

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Main goal of this study

The main question the researchers wanted to answer in this study was:Other goals of this study

Researchers also wanted to answer the following questions:•

How long did participants live with their cancer before it got worse or led to death?

•

How long did participants live after first day of treatment?

•

What side effects did the participants develop during the study?

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
not have serious side effects. The study started in
September 2017 and is expected to end in 2023.
The results were collected up to March 2019 and a study
report was created. This summary is based on that report.

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Who was in this study?
This study included 253 participants from 8 countries.

Participants could take part in this study if they:•

were at least 18 years of age•

had confirmed HER2-positive breast cancer thatwas unresectable or metastatic•

had breast cancer that was previously treatedwith T-DM1•

were either fully active OR unable to do hard physical activity but able to walk and do light houseworkor office work•

had adequate liver, kidney, bone marrow and blood clotting function, as measured by blood tests

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What happened during this study?
This was a Phase 2 study, which means that study treatment was given to a smaller number of participants
with the disease to gather information about its effects. It was open label, meaning that the researchers knew
which treatment was given to which participants, and the participants knew which treatment they received.
Participants continued to receive treatment as long as they did not show worsening of cancer, have serious
side effects, or ask to be removed from the study.

Part 1
Part 1 of the study was divided into 2 stages: a pharmacokinetic (‘PK’) stage and a dose finding stage.
PK stage: During the PK stage, researchers studied 3 different doses and based on the levels of T-DXd inparticipants’ blood, they chose 2 dose levels that could be tested in the next stage.
Participants were randomly divided into 3 groups. In all 3 groups, T-DXd was given as an injection.
Doses of 5.4 mg/kg (low), 6.4 mg/kg (medium) and 7.4 mg/kg (high) were assessed. The researchers identified
the low and medium doses as the recommended doses of T-DXd that could be given to participants in the nextstage of Part 1.
Dose finding stage:
During this stage, researchers gave the low and medium doses of T-DXd and looked at its effects and safety inthe participants to find out the recommended dose for further testing during Part 2. Based on the results, thelow dose was chosen as the recommended dose in the study.

Part 2
During Part 2, participants were included into 2 groups according to their response to T-DM1 before enrollingin this study. Group 2a (130 participants) comprised patients who had discontinued treatment with T-DM1
due to progression of their disease; Group 2b (4 participants) consisted of patients who had discontinued
T-DM1 for other reasons. Both groups received the same low dose (5.4 mg/kg).

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The following diagram shows the study stages and the different doses received by participants:

Part 1PK stage

Part 2
Dose ﬁnding stageLow dose
DS-8201a
5.4 mg/kg

Medium dose

Low dose
DS-8201a
5.4 mg/kg

DS-8201a
6.4 mg/kg

Medium dose
253 women withbreast cancer

High dose

DS-8201a
6.4 mg/kg

a. Discon�nued priortreatment due todisease progression→ DS-8201a 5.4 mg/kg

b. Discon�nued priortreatment forother reasons→ DS-8201a 5.4 mg/kg

DS-8201
7.4 mg/kg

For part 2 all participants received the low dose. They were split according to why they had discontinued treatment
with T-DM1 prior to enrolment on this study. Group (a) had discontinued due to progression of their disease, andgroup (b) had discontinued for other reasons

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 websites listed at the end of this summary.

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How many participants had tumors that completely disappeared or became
at least 30% smaller after treatment?

What were the other results of this study?
How long did participants live with their cancer before it got worse or led to death?

The median length of time participants lived with their cancer before it got worse or led to death could not be
evaluated at the time of this analysis. The cancer remained at least stable and did not worsen for the majorityof participants in these groups.
Participants who received the higher dose (7.4mg/kg) in the first part of the study, lived for a median of about

9½ months before their cancer got worse or led to death, whichever occurred first.

This means that for half of the participants who were given high dose of T-DXd, it took less than 9½ months fortheir cancer to start getting worse and for the other half of participants, it took longer.

How long did participants live after first day of treatment?

Due to the relatively small number of participants who died during the study, the length of time participants
lived since their first day of treatment could not be evaluated.

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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 treatments in the 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.
Side effects that are related to the study treatment (T-DXd) are reported here. For more information on
medical problems, please visit the websites listed at the end of this summary.

How many participants had serious side effects?

During the study, 25 out of 253 participants (10%) had serious side effects.

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The serious side effects that occurred in at least 5% (5 out of 100) of participants in any group were:
Serious side effects

Low dose(out of 184 participants)

Medium doseHigh dose(out of 48 participants) (out of 21 participants)

0

0

5%
(1 out of 21)

Swelling in the lungs

1%(1 out of 184)

0

5%
(1 out of 21)

Lung damage

1%(1 out of 184)

4%
(2 out of 48)

5%(1 out of 21)

Skin infection

0

0

5%
(1 out of 21)

Fever in patients with low
neutrophilsa

0

0

5%
(1 out of 21)

Low sodium level in blood

0

0

5%
(1 out of 21)

A certain form of damage tolung tissue0

2%(1 out of 48)

5%(1 out of 21)

General pain

0

0

5%
(1 out of 21)

Water between the lungs
and chest wall

0

0

5%
(1 out of 21)

Increase in liver test value of
aspartate aminotransferasein the bloodb

0

0

5%
(1 out of 21)

Increase in liver test value of
alanine aminotransferase in
the bloodb

0

0

5%
(1 out of 21)

Lung infection

a Neutrophils are a type of white blood cells that fight bacteria.
b An increase in blood levels of aspartate aminotransferase and alanine aminotransferase indicatesdamage to the liver.

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There were 5 deaths that were reported as possibly related to T-DXd:•

1 participant in the high dose group died due to swelling in the lungs.

•

4 participants in the low dose group died due to infection of the lymphatic vessels, swelling in thelungs, loss of ability to breathe adequately or supply enough oxygen to the blood and organs, andsudden loss of ability to breathe adequately or supply enough oxygen to the blood and organs.

How many participants had side effects?

All side effects, both serious and non-serious, are presented in this section.

The most common side effects that occurred in at least 15% (15 out of 100) of participants in any group were:
Low dose(184 participants)

Medium dose
(48 participants)

High dose(21 participants)

Decreased neutrophil* count below
normal level11%(20 out of 184)

13%
(6 out of 48)

19%(4 out of 21)

Feeling tired

44%(81 out of 184)48%
(23 out of 48)

52%(11 out of 21)

Decreased red blood cell count21%(39 out of 184)38%
(18 out of 48)

48%(10 out of 21)

Nausea76%(140 out of 184)81%
(39 out of 48)

62%(13 out of 21)

Decrease in white blood cell count17%(32 out of 184)31%
(15 out of 48)

62%(13 out of 21)

Side effects

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Low dose(184 participants)

Medium dose
(48 participants)

High dose(21 participants)

Decrease in appetite

28%(52 out of 184)42%
(20 out of 48)

24%(5 out of 21)

Vomiting

42%(78 out of 184)33%
(16 out of 48)

29%(6 out of 21)

Diarrhea

22%(40 out of 184)23%
(11 out of 48)

10%(2 out of 21)

Constipation18%(33 out of 184)29%
(14 out of 48)

38%(8 out of 21)

Headache10%(19 out of 184)

17%
(8 out of 48)

5%(1 out of 21)

Inflammation of the mouth and lips

12%(22 out of 184)27%
(13 out of 48)

19%(4 out of 21)

Hair loss

46%(85 out of 184)54%
(26 out of 48)

38%(8 out of 21)

General discomfort

3%(5 out of 184)

6%
(3 out of 48)

24%(5 out of 21)

Decreased neutrophil* count20%(36 out of 184)35%
(17 out of 48)

57%(12 out of 21)

Decreased platelet** count13%(23 out of 184)23%
(11 out of 184)33%
(7 out of 21)

Increase in liver test value of aspartate
aminotransferase in the blood

10%(19 out of 184)

8%
(4 out of 48)

29%(6 out of 21)

Increase in the liver test value ofbilirubin in the blood

4%(8 out of 184)

4%
(2 out of 48)

19%(4 out of 21)

Increase in liver test value of alkaline
phosphatase in the blood2%(4 out of 184)

4%
(2 out of 48)

24%(5 out of 21)

Increase in liver test value of alanine
aminotransferase in the blood8%(14 out of 184)

8%
(4 out of 48)

29%(6 out of 21)

A certain form of damage to lung tissue

3%(5 out of 184)

6%
(3 out of 48)

24%(5 out of 21)

Side effects*Neutrophils are a type of white blood cell that fight bacteria.
**Platelets are a type of blood cell that prevent or stop bleeding.

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How many participants had to stop treatment because of side effects?

11% of participants (28 out of 253) stopped treatment early because of side effects.

The most common side effects that led to participants stopping study treatment were lung infection, inabilityof the adrenal glands to produce enough hormones, swelling in the lungs, and a certain form of damage tolung tissue.

How was this study useful for participants and researchers?
This study helped researchers learn if T-DXd can reduce the growth of tumor cells in participants who either
did not respond to, or whose cancer came back after, treatment with T-DM1. This study also helped
researchers learn about the safety and other effects of T-DXd when given to participants with HER2 positive
metastatic and/or unresectable breast cancer. Other studies of T-DXd are ongoing.
This summary only shows the results of a single study. Other studies may have different findings. 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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Where can I learn more about this study?
You can find more information about this study on the following websites:www.clinicaltrials.gov: Use the NCT identifier NCT03248492 in the search field.
www.clinicaltrialsregister.eu/ctr-search/search: Use the EudraCT identifier 2016-004986-18 in
the search field.
https://www.clinicaltrials.jp: Use the identifier JapicCTI-173693 in the search field.
Please remember that the results on these websites 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 yourstudy site.
Full study title: A Phase 2 Multicenter, Openlabel Study of DS-8201a, an Anti-HER2-Antibody
Drug Conjugate (ADC) for HER2-positive,
Unresectable and/or Metastatic Breast Cancer
Subjects Previously Treated with T-DM1

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: 03 December 2021

This summary was prepared by Kinapse Ltd, a Syneos Health company.

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