Clinical Results Summary
A clinical study to learn about the safety and effects ofDS-8201a in participants with advanced solid tumors
Thank You!

Daiichi Sankyo Co. Ltd., 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 advanced solidtumors. Their contribution to medicine and healthcare is greatly appreciated.
Protocol number: DS8201-A-J101

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 solid tumors
A tumor is an abnormal growth of cells in the body that starts in an organ, muscle, or bone of the body. An“advanced” solid tumor usually means one that has spread to other parts of the body. A certain kind ofprotein called a ‘kinase’ helps tumor cells divide and grow. It is believed that by stopping this protein fromworking, the growth of the tumor cells can be stopped.
Some people with solid tumors have an expression of a protein called HER2, which makes their cells grow anddivide too fast. 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.
Participants enrolled in this study had some of the following types of tumors:•Breast cancer•Stomach cancer•

Gastroesophageal junction (GEJ) cancer: cancer in the area where the esophagus (a tube that carries
food from the mouth) joins the stomach•Non-small cell lung cancer (NSCLC): a cancer in which tumor cells are formed in the tissues of the lungs•

Colorectal cancer: cancer of the colon or rectum at the end of digestive system•

Other solid tumors

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. This is given for the treatment of breast cancer.
• 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- expressing solid tumors which are 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
This study had 2 parts. Part 1 involved the administration of increasing doses of T-DXd to establish
recommended and maximum doses for further study. Part 2 used the recommended doses established inPart 1 in patients with different forms of cancer.

Main goals of this study
The main questions the researchers wanted to answer in this study were:DS8201-A-J101 Clinical Results Summary | 3

Other goals of this study
Researchers also wanted to answer the following question:•Parts 1 and 2: What were the exposure levels of T-DXd*, its breakdown product MAAA-1181a, andtotal anti-HER2 antibody, in the blood of participants?

*T-DXd consists of 2 components connected by a linker. One component is a cytotoxic drug payload called DXd,
or MAAA-1181a. The other is the HER2 targeted antibody called trastuzumab. The 2 components are designed
to stay connected by the linker until T-DXd binds to a cancer cell with the HER2 marker on it. Once T-DXd binds
to an HER2-expressing cancer cell, it gets activated. The 2 components then separate and the cytotoxic drug
payload component (MAAA-1181a) kills the HER2-expressing cancer cell.

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.The study started in September 2015
and is expected to end in September 2022.
The results were collected up to February 2019 and a study
report was created. Once the study is completed, a fullsummary of the results will also be made available.

Who was in this study?
This study included 289 participants from the United States and Japan. In Part 1 the dose was increased insteps from 0.8mg/kg to 8.0 mg/kg in order to establish the recommended dose for further study. Two doses,5.4 mg/kg and 6.4 mg/kg, were selected for continued testing.

In Parts 1 and 2

In Part 1
27 participants
were enrolled

Out of 289 participants,
277 were enrolled

96% were women

4% were men

78% were women

22% were men(26 out of 27)(1 out of 27)(215 out of 277)

(62 out of 277)

Participants had an average age of 62 years

Participants had an average age of 55 years

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Participants could take part in this study if they:•were at least 20 years old in Japan and at least 18 years old in the United States,•

were either fully active or unable to do a hard physical activity but able to walk and do light work,•had one of the following advanced tumors that came back after standard treatment or could not betreated by standard treatment or for which no standard treatment was available:o Part 1: breast cancer. stomach cancer or GEJ cancero Part 2a: breast cancer with an increased level of HER2 that had been previously treated withT-DM1 (also known as trastuzumab emtansine)o Part 2b: stomach or GEJ cancer with an increased level of HER2 that had been previously treatedwith trastuzumabo Part 2c: breast cancer with a low level of HER2o Part 2d: other solid cancers that spread to other parts of the body with HER2 expressiono Part 2e: breast cancer with HER2 expression for which no standard treatment is available

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
number of participants. This helps researchers understand what happens to the study treatment in the body,and if there are any side effects.
This was an “open label” study, which means that both the researchers and the participants knew what doseof T-DXd the participants were given.
Two types of drug products were used in this study. Participants in Part 1 and Parts 2a, 2b, 2c, and 2d received
drug product formulation 1 (50mg/2.5 mL injection). Participants in Part 2e received drug productformulation 2 (100 mg/5 mL injection); Part 2e was conducted at Japanese sites only.

Part 1
Part 1 of the study was called ‘dose escalation’. Dose escalation studies are done to find the maximum dose ofa drug that can be safely given to participants and the dose that is recommended for further study.
In Part 1, 27 participants with advanced solid tumors were assigned to 6 groups. Researchers started by giving
0.8 milligrams (mg)/kg of T-DXd to the first group of participants. If this dose was considered to be safe by theresearchers, the next group of participants received a higher dose of T-DXd. This process was repeated withincreasingly higher doses, as shown in the study design figure below until the highest dose that could safely begiven was identified.

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For all groups, T-DXd was given by injection every 3 weeks. Participants continued to receive treatment as longas they did not show worsening of their tumor or have serious side effects, or they asked to be removed fromthe study.
The maximum tolerated dose of T-DXd was not achieved in Part 1. The researchers identified 5.4 mg/kg and6.4 mg/kg of T-DXd to be given to participants in Part 2.

Part 2Part 2 of the study was called ‘dose expansion’. Dose expansion studies are done to find the safety and effectsof the drug in a larger group of participants at the dose that was selected during dose escalation. In Part 2, 5.4
mg/kg or 6.4 mg/kg of T-DXd was given to participants with different types of solid tumors on the first day ofsuccessive 21-day cycles. For all groups, T-DXd was given was given directly into the vein.

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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.

Part 1: Which was the recommended and maximum dose of T-DXd?

In this trial, doses of 5.4 mg/kg and 6.4 mg/kg were recommended for further study. The maximum dose ofT-DXd patients could tolerate was not reached.

Parts 1 and 2: How many participants had cancer that completely disappeared orbecame at least 30% smaller after treatment?
This was based on measures from imaging (scans). Results were available for 277 participants who wereenrolled to either 5.4 mg/kg or 6.4 mg/kg of T-DXd. This included data from 12 participants from the dose
escalation phase and 265 participants from dose expansion phase who received 5.4 mg/kg or 6.4 mg/kg ofT-DXd.

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Parts 1 and 2: How many participants had side effects during this study?

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.
The answers to this question are presented in the section ‘What medical problems did the study participants
have’.

What was the other result of this study?
Parts 1 and 2: What were the exposure levels of T-DXd, its breakdown product
MAAA-1181a, and total anti-HER2 antibody, in the blood of participants?

To answer this question, researchers measured the levels of T-DXd, MAAA-1181a, and anti-HER2 antibody inthe participants’ blood for different doses after the first dose of treatment.
The average results of these measurements are presented below. Concentration of T-DXd, MAAA-1181a, andanti-HER2 antibody in the participants’ blood are measured in μg (micrograms) * d/mL for T-DXd andng (nanograms) * d/mL for MAAA-1181a.
Researchers found that the total exposure levels of T-DXd, MAAA-1181a, and total anti-HER2 antibody in theparticipants’ blood increased with increasing doses.

Part 1 – Total exposure levels
0.8 mg/kg

1.6 mg/kg

3.2 mg/kg

5.4 mg/kg

6.4 mg/kg

8.0 mg/kg

T-DXd

52116

325

544

901

996

Anti-HER2 Antibody

84

200

302

609

878

1120

MAAA-1181a

59244131

40

Dose Escalation

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The total exposure levels of T-DXd, MAAA-1181a, and total anti-HER2 antibody in Parts 1 and 2 are presented
by cancer type for the doses 5.4 mg/kg and 6.4 mg/kg as shown below. Researchers found that the total
exposure levels of T-DXd in blood were higher at 6.4 mg/kg when compared to 5.4 mg/kg. The total exposurelevels of total anti-HER2 antibody were similar to T-DXd. MAAA-1181a exposure levels were lower than that ofT-DXd or total anti-HER2 antibody. However, the exposure levels of T-DXd and total anti-HER2 antibody inblood were lower in HER2-expressing GC high cancer.

Parts 1 and 2 – Total exposure levels by 5.4 mg/kg doseBC high
5.4 mg/kg

GC high
5.4 mg/kg

BC low
5.4 mg/kgT-DXd

564

524

582

Anti-HER2 Antibody

771

683

659

MAAA-1181a3643

42

All participants

Parts 1 and 2 – Total exposure levels by 6.4 mg/kg doseBC high
6.4 mg/kg

GC high
6.4 mg/kg

BC low
6.4 mg/kg

Other
6.4 mg/kg

T-DXd

788

520

685

631

Anti-HER2 Antibody

1020

609

761

688

MAAA-1181a

42434449

All participants

BC high: HER2-overexpressing breast cancer; GC high: HER2-overexpressing stomach or GEJ cancer;
BC low: HER2-low expressing breast cancer.

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. These results
were available for 289 participants who received any doses of T-DXd. The websites listed at the end of thissummary 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.

DS8201-A-J101 Clinical Results Summary | 9How many participants had serious side effects?

Overall, serious side effects observed by the dose group in Parts 1 and 2 are presented below.

6 participants (2%) taking T-DXd died of causes associated with side effects during this study. The
cause of death included lung damage or inflammation in the lung tissues, insufficient oxygen in thelungs, abnormally low number of neutrophils accompanied with fever, liver damage, and abnormal
blood clotting in the blood vessels.

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How many participants had side effects?

The most common side effects, which happened in at least 20% (20 out of 100) of participants in any dosegroup in Parts 1 and 2 are presented below.

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

How was this study useful for patients and researchers?
This was a first in humanstudy. It helped researchers learn about the safety and effects of T-DXd inparticipants with advanced solid tumors.
Findings from this study may be used in other studies to learn whether patients with advanced solid tumors
are helped by this treatment. Other studies for 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.

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 NCT02564900 in the search field.
https://www.clinicaltrials.jp: Use the identifier JapicCTI-152978 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.

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Full study title: Phase 1, Two-part, Multicenter,
Non-randomized, Open-label, Multiple-dose,First-in-human Study of DS-8201a, in Subjects
with Advanced Solid Malignant Tumors

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 June 2022

This summary was prepared by Syneos Health®.

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