Clinical Results Summary
A clinical study to learn about the safety and effects of DS-8201a inparticipants with HER2-positive cancer that has spread and/or isdifficult to treat
Protocol number: DS8201-A-A103

Thank You!

Daiichi Sankyo, 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 people affected with HER-2 positivecancer. 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?
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 cancers have an increased level of a protein called HER2, which makes their cells grow anddivide too fast. This is called a HER2-positive cancer. DS-8201a, also known as trastuzumab deruxtecan orT-DXd, specifically binds to HER2-expressing cells to inhibit the cell growth and cause the death of target
tumor cells.
Participants could take part in this study if they had HER2-positive cancer of one of the following types:•Gastric (stomach) cancer•

Gastroesophageal junction (GEJ) cancer: cancer in the area where the food pipe and stomach join
together•Breast cancer

At this time treatment options for the above mentioned cancers are:• surgery• radiation therapy - a treatment that uses radiation to kill cancer cells• endocrine (hormone) therapy - a treatment that stops the growth of cancers 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 safety and effects of T-DXd in participants withHER2-positive advanced cancer which is refractory. Refractory means that the cancer does not respond to or
cannot be treated with available treatment options.

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Treatment given in this study

T-DXd
Drug being studied for the treatment
of HER2-positive advanced and/or
refractory cancer

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 question:•What were the levels of T-DXd*, its breakdown product MAAA-1181a, and total anti-HER2 antibody, inthe blood of participants?

*T-DXd 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 T-DXd binds to a cell with the HER2
marker on it. Once T-DXd binds to a HER2 positive cell, it gets activated. The 2 components then separate anda released topoisomerase I inhibitor (MAAA-1181a) kills the HER2 positive cell.

DS8201-A-A103 Clinical Results Summary | 2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 andthey did not have serious side effects, or were asked to be
removed from the study. The study started in April 2018
and is expected to end in April 2022.
The results were collected up to September 2018 and astudy report was created. Once the study is completed, afull summary of results will also be made available.

Who was in this study?
This study included 12 female participants (of Chinese
descent) with breast cancer.
Participants could take part in this study if they:•

were either fully active or able to walk and do lightwork but unable to do a hard physical activity,•

were expected to live for at least 3 months,•

had breast cancer that came back after standard
treatment or could not be treated by standard treatment or for which no standard treatment wasavailable,•

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

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 smallnumber of 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 dose ofT-DXd the participants were given.
Participants received 6.4 milligram/kilogram (mg/kg) of T-DXd through a drip over 90 minutes on the first dayof each cycle for a minimum of 3 cycles. Each cycle lasted 3 weeks.
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Researchers took blood samples from participants at defined time points. Researchers monitored theparticipants’ health throughout the study.

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.

How many participants had side effects during the study?
During this study, all the participants (12 out of 12, 100%) had at least 1 side effect.
Detailed information about side effects reported by participants is presented in the section ‘What medical
problems did the participants have?

What were the levels of T-DXd, its breakdown product MAAA-1181a, and total
anti-HER2 antibody, in the blood of participants?
To answer this question, the researchers measured the total levels of T-DXd, MAAA-1181a and anti-HER2
antibody in the participant’s blood samples during Cycle 1 and Cycle 3.
The average results of these measurements are presented below. Total levels of T-DXd, MAAA-1181a, andanti-HER2 antibody in the participants’ blood is measured in d × ng hr/mL*.

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Researchers found that the levels of T-DXd, MAAA-1181a, and anti-HER2 antibody in the participants’ bloodincreased from Cycle 1 to Cycle 3.

*This means the total levels of T-DXd, MAAA-1181a, and total anti-HER2 antibody in nanograms (one thousand-millionthof a gram) found in each milliliter of blood within the dosing period.

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 T-Dxd. 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 thisstudy.
Side effects are considered serious if they cause death, are life-threatening, cause lasting problems, or require
hospitalization.

How many participants had serious side effects?
In this study, 1 out of 12 participants (8%) had a serious side effect of abnormally low levels of neutrophils (atype of white blood cell that fights bacteria) accompanied with fever.

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How many participants had side effects?
All side effects, both serious and non-serious, are presented in this section. All the participants (12 out of 12,100%) had at least 1 side effect.
The most common side effects that occurred in at least 25% of participants (3 out of 12) were:
T-DXd (6.4 mg/kg)(out of 12 participants)
58%
Decrease in platelet count a(7 participants)
Increase in liver test value of aspartate
42%
baminotransferase (AST) in the blood(5 participants)
42%
Decrease in white blood cells count c(5 participants)
58%
Nausea(7 participants)
25%
Decrease in red blood cells count(3 participants)
33%
Decrease in appetite(4 participants)
25%
Feeling tired(3 participants)
a platelets are a type of blood cell that helps in preventing / stopping bleedingb an increase in AST may indicate a liver problems
c white blood cells help protect your body from infection
d red blood cells help carry oxygen around the body
Side Effects

How many participants had to stop treatment because of side effects?
No participant had to stop T-Dxd treatment because of side effects.

How was this study useful for patients and researchers?
This study also helped researchers learn about the safety and other effects of T-DXd when given toparticipants with HER2-positive advanced/refractory 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 toa 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 website:www.clinicaltrials.gov: Use the NCT identifier NCT03368196 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: Phase 1, Multicenter, Open-Label
Study of DS-8201a to Assess Safety andPharmacokinetics in Subjects with HER2-Positive
Advanced and/or Refractory Gastric,
Gastroesophageal Junction Adenocarcinoma, orBreast 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: 28-Feb-2022

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

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