Clinical Results Summary
A clinical study to understand the effects of Pexidartinib on liver
enzymes CYP3A4 and CYP2C9 in people with cancer
Protocol number: PL3397-A-U126

Thank You!

Daiichi Sankyo, Inc., the sponsor of this study, would like to thank the participants who
took part in this study for pexidartinib also known as PLX3397. Each participant helped toadvance medical research for people affected with 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.

PL3397-A-U126 Clinical Results Summary | 0What was the main purpose of this study?
Pexidartinib, the study drug being tested, stops the growth of tumor cells by preventing the protein ‘kinase’
from working.
Earlier studies have shown that pexidartinib could stop the action of certain liver enzymes. Liver enzymes
CYP3A4 and CYP2C9 are responsible for breaking down several drugs into active and inactive products in thebody. In this study, researchers wanted to learn how pexidartinib affects the blood levels of drugs broken
down by these enzymes. They chose to study the levels of drugs midazolam and tolbutamide. CYP3A4 breaks
down midazolam and CYP2C9 breaks down tolbutamide.
Researchers also wanted to understand the effects and safety of pexidartinib for treating various tumours.

Treatments given in this study
The treatments given in this study werePexidartinib(Study drug)
Drug being studied for the treatment oftumors. 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.

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

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How long was this study?
The study was designed in such a way that theparticipants could continue taking pexidartinib
during the study for as long as the treatment
benefited the participants without any serious
side effects.
The study started in March 2018 and ended in
March 2021. Results were collected up toMarch 2021 and a study report was created.
This summary is based on that report.

Who was in this study?
This study included 30 participants from the United States, the Netherlands, New Zealand, and Taiwan.
Participants could take part in this study if they:•were 18 years and above,•had tumor growth in or around the joint due totenosynovial giant cell tumor (TGCT), skin cancer,
stomach cancer, or other solid tumors for which
there was no standard treatment, and•had normal blood, liver, and kidney function thatwere within the range specified for the study.

In this study
30 participants took part
50% were women(15 out of 30)

50% were men(15 out of 30)

Participants had an average age of 51 years

What happened during this study?
This was a Phase 1 study. Phase 1 studies are done to find out how a new study drug works in a small numberof participants. This helps researchers understand what happens to the study drug in the body, and if there
are any side effects. This study was also “open label”. This means that both the researchers and theparticipants knew which treatment was given to participants.

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Participants first completed a screening period to find out if they could take part in the study.
This study was done in 2 parts:

Part 1
Part 1 of the study was done to understand how pexidartinib affects midazolam and tolbutamide
in the body. A total of 30 participants were treated in Part 1 of this study.
On Day 1, participants received a single dose of 2 milligrams (mg) of midazolam and 500 mg tolbutamide.
Starting from Day 3, participants received 400 mg of pexidartinib capsules twice a day until Day 15. On themorning of Day 3, participants also received a single dose of midazolam (2 mg) and tolbutamide (500 mg).
On Day 13, participants received the same doses of pexidartinib, midazolam, and tolbutamide as Day 3.
Researchers collected blood samples from participants at regular intervals on Day 1, Day 3, and Day 13 andmeasured the blood levels of all the drugs.

What happened in this study
Part 1
Day 1

Day 3

Day 13

Midazolam andtolbutamide

Pexidartinib,midazolam andtolbutamide

Pexidartinib,midazolam andtolbutamide

30 participants

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Part 2Participants who completed treatment during Part 1, entered Part 2 of the study. In Part 2, 25 participants
continued to receive pexidartinib 800 mg daily, for as long as they benefited from the treatment without any
serious side effects.
The researchers used magnetic resonance imaging (MRI), and computed tomography (CT) scan to check theparticipants’ tumor size. They closely monitored the health of the participants.

What happened in this study
Part 2Participants received Pexidartinib
daily in a treatment cycle of 28 days

25 participants

The safety of the participants wasmonitored in Part 2.

Treatment continued
as long as
participants did notshow worsening ofcancer, have serious
side effects, or asked
to be removed fromthe study.

All participants in Part 2 discontinued the study.

What was the key result 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.

PL3397-A-U126 Clinical Results Summary | 4What was the effect of pexidartinib on the blood levels of midazolam andtolbutamide in participants?
Compared to when midazolam was given alone on Day 1, the blood levels of midazolam decreased by 21%
after a single dose of pexidartinib on Day 3. By Day 13, the blood levels of midazolam decreased by 52% after
multiple doses of pexidartinib. This means that pexidartinib increased the rate at which CYP3A4 worked andbroke down midazolam.
Compared to when tolbutamide was given alone on Day 1, the blood levels of tolbutamide increased by 15%
after a single dose of pexidartinib on Day 3. By Day 13, the blood levels of tolbutamide increased by 36% after
multiple doses of pexidartininb. This means that pexidartinib reduced the rate at which CYP2C9 worked andbroke down tolbutamide.

How was this measured?
Researchers collected blood samples and measured the total levels of midazolam and tolbutamide inparticipants’ blood on Day 1, Day 3, and Day 13 in units, nanograms hours per milliliter (ng•h/mL). This shows
how much midazolam and tolbutamide in nanograms (one thousand-millionth of a gram) was found in eachmilliliter of blood over time.

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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
doctors thought could be related to the treatments in the study. This section provides a summary of side
effects related to pexidartinib. The websites listed at the end of this summary have 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 related to pexidartinib?
Serious side effects reported by participants in both Part 1 and Part 2 are presented below:

No deaths were reported due to side effects.

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How many participants had side effects related to pexidartinib?
The most common side effects, reported by more than 10% of participants in either Part 1 or Part 2 arepresented below:

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How many participants had to stop treatment because of side effects?
None of the participants in Part 1 stopped taking pexidartinib due to side effects.
In Part 2, 8% (2 of 25) participants stopped taking pexidartinib because of side effects of increase in liver test
value of bilirubin and allergic reaction to the drug.

How was this study useful for patients and researchers?
This study helped researchers learn how pexidartinib affects the blood levels of drugs that are broken down by
the liver enzymes CYP3A4 and CYP2C9 Findings from this study may be used in other studies withpexidartinib. Other studies of pexidartinib are ongoing.
Please remember, 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.

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 NCT03291288 in the search field.
www.clinicaltrialsregister.eu/ctr-search/search: Use the EudraCT identifier 2020-000192-20 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: An Open-Label, Single Sequence,
Crossover Drug-Drug Interaction Study Assessing
the Effect of Pexidartinib on thePharmacokinetics of CYP3A4 and CYP2C9
Substrates in Patients

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: 08 June 2023

This summary was prepared by Syneos Health®.
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