Clinical Results Summary
A clinical study to learn more about the effects and safety ofpexidartinib in people with tumor growth in or around the joint due totenosynovial giant cell tumor (TGCT)
Also called: ENLIVEN
Protocol number: PLX108-10

Thank You!

Daiichi Sankyo, Inc., the sponsor of this study, would like to thank the participants who
took part in this study for PLX3397, also known as pexidartinib. Each participant helped toadvance medical research for people affected with tumor growth in or around the joint, acondition known as tenosynovial giant cell tumor, or TGCT. 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 anytreatment you are taking or if you have any questions about these study results.
Clinical Results Summary | 1What was the main purpose of this study?
Tenosynovial giant cell tumor

Tenosynovial giant cell tumor (TGCT) is a condition in which people have tumors that grow in and around theirjoints. Localized TGCT is more common and usually affects small joints, such as the hands and ankles. Diffuse
TGCT is less common and affects large joints, such as the hips and knees. This condition causes pain, stiffness,swelling, and a decrease in the range of movement of the joints.
At this time, the main treatment option for TGCT is surgery. However for some people, tumors can come backeven after surgery. For others, doctors may not recommend surgery if the tumor has grown or has invaded thejoint too much. For all of these patients, new methods of treating TGCT are needed.
Researchers think these tumors form when some cells in the joint start making too much of a protein that
attracts other cells to the joint. As more and more cells reach the joint, they join together to form tumors.
Pexidartinib is a treatment that may stop this protein from attracting cells. In this study, researchers wanted
to see if pexidartinib could be used to shrink the tumors or stop new tumors from growing in and around thejoints for people who have TGCT.

Treatments given in this study
Pexidartinib: A treatment being studied for its ability to shrink the tumor in or aroundthe joint and to stop new tumors from forming. When the study started, pexidartinib
was not approved for use. This means that it could only be used in a research study
such as this one.
Placebo: A placebo looks like the study treatment and is given in the same way, but it
does not have any medicine in it. Using placebo helps researchers better understandthe effect of a study treatment.

Main purpose of this study

The main question the researchers wanted to answer in this study was:Clinical Results Summary | 2

The researchers also wanted to learn more about the safety of pexidartinib. Additionally, they tracked
participants’ joint movement, stiffness, ability to perform daily activities, intensity of pain, and use of pain
medication.

How long was this study?
An individual participant could have stayed in Part 1 of thestudy for about 6 months. Depending on their treatment groupin Part 1, the same participants could have stayed for Part 2
and continued treatment with pexidartinib.
Part 1 and Part 2 results were evaluated up to 31 January 2018
and a study report was created. This summary is based on thatreport. Once Part 2 of the study is completed, a full summaryof results will also be made available to all participants.

Who was in this study?
This study included 120 participants from the following countries:

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Participants could take part in this study if they:•were over 18 years of age,•

had TGCT and doctors considered that surgery
could have caused more harm than good,•

had normal blood, liver, and kidney function,•suffered from pain and stiffness that interferedwith their daily activities, and•did not have any other type of active cancer thatneeded treatment, aside from a few exceptions.

What happened during this study?
This was a large, global, Phase 3 study that compared the effects and safety of pexidartinib with placebo in
participants with TGCT who had tumor growth in or around their joints. Participants in Part 1 had the option tocontinue on to Part 2.

Part 1

Participants completed a screening period to find out if they could be a part of the study. The researchers thenused a computer program to randomly assign participants into 2 groups, Group 1 and Group 2, a process
called randomization. This means that each person had an equal chance of being in any group. Participants inGroup 1 received pexidartinib as capsules 2 times a day, for 24 weeks. Participants in Group 2 received
placebo as capsules 2 times a day, for 24 weeks. This part was double-blinded, meaning neither theparticipants nor the study doctors knew who took which treatment.
The researchers used a special scan, called magnetic resonance imaging or MRI, to measure the participants’
tumor size during the study at different times.
They also closely monitored the health of the participants throughout the study.

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Part 2
Part 2 was an open-label study, which means thatboth the researchers and the participants knew
what treatment was given. All participants in Part 2
received 800 mg pexidartinib as capsules 2 times aday. The study was designed so that all participants
who completed Part 1 (Group 1 and Group 2) could
advance to Part 2.

Changes to the study plan

In the early stages of the study, an independent committee was asked to monitor the overall health of allparticipants. During the study, there were 2 participants who showed signs of serious liver problems. One ofthese participants required hospitalization and 2 liver dialysis procedures. Study treatment was discontinued
Clinical Results Summary | 5

for both participants. On 29 September 2016, the independent monitoring committee carefully reviewed thehealth data. After review, to ensure the safety of all participants in the study, the sponsor made the followingchanges to the study design:•Researchers did more liver tests more often to monitor participants’ liver function and overall health.

•Only participants who were in the pexidartinib group of Part 1 could advance to Part 2.

•Participants in the placebo group could no longer advance to Part 2 after they completed Part 1.

•No new participants were allowed to start the study.

Overview of study after committee review

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.
Clinical Results Summary | 6How many participants had tumors that completely disappeared or had tumorsthat became 30% smaller after about 6 months of treatment?

What were the other results of this study?
Participants taking pexidartinib showed greater improvement in range of motion of the joints, tumor-related
stiffness of affected joints, and ability to perform daily activities. Participants in pexidartinib group who
responded to pexidartinib maintained the response to treatment.
More participants who took pexidartinib reported a decrease in pain and use of pain medication. However,this decrease may have been due to chance and not caused by the study treatment.

What medical problems did the study participants have?
Side effects are medical problems (such as 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 stopped study treatment because of side effects.

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How many participants had serious side effects during Part 1?

In this study, side effects were monitored for 61 participants who took pexidartinib and 59 participants who
took placebo.

How many participants had serious side effects while taking pexidartinib during
the study?

The first row labeled ‘Total Pexidartinib Participants’ shows total percentage of serious side effects reported
by participants who received pexidartinib during Part 1 and 2. The second row labeled ‘Cross-over Pexidartinib
Participants’ shows serious side effects in participants who crossed over to receive pexidartinib in Part 2 after
receiving placebo in Part 1. The third row labeled ‘All Participants’, shows the serious side effects reported by
all the participants who received pexidartinib either in Part 1 or Part 2.

Clinical Results Summary | 8

There was one participant’s death reported.
The cause of death was not related to study treatment.

What were the most common side effects during Part 1?
Side effects reported in Part 1, both serious and non-serious, are presented in this section.

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The most common side effects that occurred in at least 10% (10 out of 100) of participants in any group arepresented below:

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What were the most common side effects while taking pexidartinib during thestudy?
Side effects reported by participants taking pexidartinib, both serious and non-serious, are presented in thissection.

The most common side effects that occurred in at least 10% (10 out of 100) of participants in any group arereported below:Clinical Results Summary | 11

Clinical Results Summary | 12

How many participants had to stop treatment because of side effects during
Part 1?

The most common side effects that caused participants to stop the study treatment
in Part 1 were related to liver problems. Liver problems were in line with side
effects usually reported in other studies of this kind.

How many participants had to stop treatment because of side effects while
taking pexidartinib during the study?

How was this study useful for patients and researchers?
This study helped researchers learn about how well pexidartinib is able to remove or reduce the size of tumors
in people with TGCT who have tumor growth in or around their joints.
Findings from this study may be used to seek approval to use study treatment in patients with tumor growthin or around their joints. Other studies of pexidartinib are ongoing.
Please remember, 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
Clinical Results Summary | 13medical science and healthcare. Do not use the results of this study to make health decisions. Please talk to adoctor 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 NCT02371369 in the search field.
www.clinicaltrialsregister.eu: Use the EudraCT identifier 2014-000148-14 in the search field.
https://www.nccn.org/professionals/physician_gls/default.aspx: The National Comprehensive
Cancer Network® (NCCN) clinical practice guidelines in oncology: soft tissue sarcoma—v4.2019.
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 Double-blind, Randomized,Placebo-controlled Phase 3 Study of Orally
Administered PLX3397 in Subjects with
Pigmented Villonodular Synovitis or Giant Cell
Tumor of the Tendon Sheath (ENLIVEN)

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: 15 Jun 2020

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

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