Clinical Results Summary
A clinical study to understand the response of participants withrecurring brain cancer to PLX3397 treatment
Protocol number: PLX108-04

Thank You!

Daiichi Sankyo, Inc., the sponsor of this study, would like to thank the participants who
took part in this study for PLX3397. Each participant helped to advance medical researchfor people who have a type of brain cancer called glioblastoma. Their contribution tomedicine 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.

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What was the main purpose of this study?
Glioblastoma Multiforme (GBM)

Researchers were looking for a better way to treat people with a type of cancer called glioblastoma, orglioblastoma multiforme (GBM). GBM is a cancer of the brain or the spinal cord. The spinal cord is a long
structure made up of nerve tissue, which extends from the brain to the lower back and helps control different
functions of the body. GBM occurs due to damage to the cells that keep the brain healthy. Symptoms
experienced by people who have GBM include headache, vomiting, and feeling sick to their stomach. Thesesymptoms can get worse and lead to unconsciousness.
The main treatment for GBM is surgery followed by chemotherapy. Chemotherapy uses medicine to kill cancer
cells or stop them from growing and dividing. GBM does not always respond well to treatment and is likely tocome back. The participants in this study had GBM that came back after treatment. In this study, researchers
wanted to understand how participants with GBM that came back after treatment respond to PLX3397.

Treatment given in this study

Main purpose of this study

The main questions the researchers wanted to answer in this study were:•How many participants had cancer that did not get worse or lead to death for at least 6 months after
the start of study drug?

•How many participants were alive at the end of the study?

•What were the levels of PLX3397 in the blood of participants?

•How much time did it take to reach the highest level of PLX3397 in the blood?

Researchers also closely monitored the health of the participants throughout the study.
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How long was this study?
The study was designed in such a way that the participants could
continue in it as long as their cancer did not get worse and they did
not have serious side effects.
This study started in December 2011 but was stopped early, inNovember 2013. The study was stopped early because the treatment
did not show much response in participants with GBM. Researchers
believed that the main purpose of the study would not be achieved
even after enrolling more participants in the study, so they stopped
enrolling participants. Results were collected up to November 2013
and a study report was created. This summary is based on thatreport.

Who was in this study?
This study included 38 participants from the United States.
Participants could take part in this study if they:•

were 18 years or older and expected to live for at least
8 weeks•

had recurring GBM that had previously been treated•

could provide samples of their tumors as slides
from any previous GBM surgery•

had recovered satisfactorily from side effects of priortreatments•

had adequate blood, liver, and kidney function

What happened during this study?
This Phase 2 study was an open label study. This means both the participants and researchers knew which
treatment was given to which participants. In Phase 2 studies, the study drug is given to a small number ofparticipants with the disease condition to gather information about the effects of the study drug in patientsand to find the best dose.
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Participants first completed a screening period to find out if they could be a part of the study. The researchersthen assigned the participants to 2 groups: Group 1 and Group 2.
Participants who needed surgery to remove the tumor were assigned to Group 1. In this group, participants
took PLX3397 by mouth twice a day for 7 days before surgery. After surgery, participants continued to take
PLX3397 twice a day in 4-week cycles. When sufficient levels of PLX3397 were found in the tumor tissue
samples of at least 5 out of 10 participants in Group 1, researchers started treatment for Group 2.
Participants who did not need surgery to remove the tumor were assigned to Group 2. In this group,participants took PLX3397 by mouth twice a day in 4-week cycles.
Treatment in both groups could be continued for as long as participants did not show worsening of cancer, didnot have serious side effects, or asked to be removed from the study. The researchers used a scan called
magnetic resonance imaging, or MRI, to measure the participants’ tumor size every 8 weeks. They also tookblood samples throughout the study to measure the levels of PLX3397 in the blood.

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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 website listed at the end of this summary.

How many participants had cancer that did not get worse or lead to death forat least 6 months after the start of study drug?

How many participants were alive at the end of the study?

PLX108-04 Clinical Results Summary | 5What were the levels of PLX3397 in the blood of participants?
To answer this question, researchers measured the following:• Total level of PLX3397 in the participants’ blood 4 hours after PLX3397 was taken.
• Total level of PLX3397 in the participants’ blood 6 hours after PLX3397 was taken.
• Highest level of PLX3397 in the participants’ blood after treatment.
The average results of these measurements are presented below. Total level of PLX3397 in the participants’blood is measured in ng*hr/mL. Total level of PLX3397 in the participants’ blood after 4 hours means how
much of PLX3397 in nanogram (one thousand-millionth of a gram) was found in each milliliter of blood after
4 hours of taking PLX3397 capsule.

How much time did it take to reach the highest level of PLX3397 in the blood?
It took about 2 hours for PLX3397 to reach the highest level in the blood in both Group 1 and Group 2.

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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
doctor thought could be related to the treatments in the study. This section provides a summary of sideeffects related to the study drug PLX3397. The website listed at the end of this summary has more information
about all 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. No deaths were reported due to side effects. No participant discontinued from this study dueto a side effect.

How many participants had serious side effects?

In this study, side effects were monitored for 38 participants who took PLX3397. 5 participants experienced
serious side effects related to the study drug.

In Group 1, 1 participant had a lung infection. In Group 2, 4 participants experienced the serious side effects
listed below.
•Decreased white blood cell count•

Increase in liver test values of aspartate aminotransferase and alanine aminotransferase in the blood andincrease in INR. INR is ‘international normalized ratio’, which measures how much time it takes for theblood to clot. A high INR value means that a participant's blood is taking a longer time to clot than normal.

•Decreased red blood cell count and sodium levels in the blood, as well as dehydration.

•Abnormally low number of neutrophils accompanied with fever. Neutrophils are a type of white blood cells
that help fight infections.

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How many participants had the most common side effects?
The most common side effects, both serious and non-serious, that occurred in at least 10% of participants arereported below.

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How was this study useful for patients and researchers?
This study helped researchers learn if PLX3397 was safe and if it was effective in helping participants with atype of brain cancer called GBM that had returned after treatment. The study was stopped early because
treatment with PLX3397 did not provide much benefit to the participants with GBM. Therefore, theresearchers decided not to enroll more participants in the study.
Findings from this study may be used in other studies with PLX3397. Other studies of PLX3397 are stillongoing.
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 website:www.clinicaltrials.gov: Use the NCT identifier NCT01349036 in the search field.
Please remember that the results on this website 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 Study Of Orally
Administered PLX3397 In Patients With
Recurrent Glioblastoma

Sponsor: Daiichi Sankyo, Inc.
Sponsor contact information:
211 Mount Airy Road, Basking Ridge, NJ 07920
E-mail: CTRInfo@dsi.com
Phone number: 1-908-992-6640
Date of this summary: 04 Sep 2020

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

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