Clinical Results Summary
A clinical study to learn about the safety and effects of PLX3397 inpeople with a type of returning or treatment-resistant blood cancer
called acute myeloid leukemia
Protocol number: PLX108-05

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 affected with a type of blood cancer called acute myeloid leukemia. 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.

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What was the main purpose of this study?
Returning or treatment-resistant FLT3-ITD positive AML
Researchers were looking for a better way to treat people with a type of blood cancer called acute myeloid
leukemia, or AML. The participants in this study had AML that either:•responded to treatment, but their cancer returned within 6 months (known as relapsed AML), or•

did not respond to first treatment (known as refractory AML).

AML is a type of cancer of the blood and the bone marrow. The bone marrow is found in the center of mostbones, where new healthy blood cells are made. AML starts in the bone marrow and prevents it from making
normal blood cells. The abnormal (cancer) cells build up in the bone marrow and can also enter the bloodstream and move to different parts of the body.
The most common treatment for AML is chemotherapy. Chemotherapy uses medicine to kill cancer cells or
stop them from growing and dividing. People with AML might also have a procedure called a stem celltransplant, which removes the cancerous cells from the bone marrow and replaces them with healthy cells
from another healthy person (donor). The new cells can then multiply and produce more healthy cells.
People who have AML may have certain gene alterations (or mutations). People with FLT3-ITD positive AML
have an alteration in the FLT3 gene. FLT3-ITD positive AML is often severe, does not respond well to standard
treatment, and is likely to come back even after treatment. PLX3397, the study treatment, is a drug designed
to work against AML cancer cells by stopping the activity of this gene mutation.

Treatment given in this study

PLX108-05 Clinical Results Summary | 2Main goal of this study
The main question researchers wanted to answer in this study was:Other goals of this study
Researchers also wanted to answer the following questions:•How many participants had at least 50% reduction in AML after treatment?

•What were the participants condition and life duration after initial response to PLX3397 treatment?

Researchers also closely monitored the health of the participants throughout the study.

How long was this study?
The study was designed so that participants could
continue in it as long as their cancer did not get worse
and they did not have serious side effects. The study
started in November 2011 and ended in January 2018.
The results were collected up to January 2015 and astudy report was created. This summary is based onthat report. The study ended as planned inJanuary 2018.

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Who was in this study?
This study included 90 participants from the United States.
Men and women could take part in this study if they:•were 18 years of age or older,•either did not respond to their first treatment for AML, their cancer returned within 6 months ofreceiving treatment, or they had been newly diagnosed with FLT3-ITD positive AML and standard
treatment could not be used,•tested positive for the FLT3-ITD mutation at the time of entering into the study,•

agreed to a bone marrow analysis to enter into Part 2,•

had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2, meaning they
were either fully active, unable to do hard physical activity but able to walk and do light work, orunable to work but able to walk and manage selfcare, and•had adequate liver and kidney function.

What happened during this study?
This was a Phase 1/2 study that was divided into 2 parts. Part 1 was a Phase 1 study, which are sometimes
done to find the highest dose of a drug that can be safely given to participants. Part 2 was a Phase 2 study
done to better understand if a drug can treat the condition it has been developed for.
This study was also “open label”. This means that both the researchers and the participants knew which
treatment was given to which participants. Participants first completed a screening period to find out if they
could take part in the study. 90 participants who passed screening were assigned to 2 groups: 34 participantsin Part 1 and 56 participants in Part 2.

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In Part 1, researchers started by giving 800 milligrams (mg) of PLX3397 to the participants in Group 1. If thisdose was considered to be safe by the researchers, the next group of participants received a higher dose ofPLX3397. This process was repeated with increasingly higher doses, as shown in the study design figure below,
until the highest dose that could safely be given was identified. For all groups, PLX3397 was given by mouth
twice daily for a total of the dose being studied for that group. The researchers identified 3000 mg as thehighest dose of PLX3397 in Part 1 that could safely be given to participants.
In Part 2, this dose of 3000 mg PLX3397 was given to all participants to learn about their response totreatment. The participants in both parts continued to receive treatment as long as they did not show
worsening of cancer, have serious side effects, or asked to be removed from the study.

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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 participants’ 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 showed either a complete response to treatment withPLX3397 or discontinued treatment to have a stem cell transplant?
To answer this question, researchers recorded the total number of participants who either:•

showed a complete response to treatment, meaning they hado complete disappearance of AML with complete recovery of neutrophil count, oro complete disappearance of AML, with or without complete recovery of neutrophil count orplatelet count•had a stem cell transplant procedure and therefore discontinued study treatment

Neutrophils are a type of white blood cells that help fight infections. Platelets are a type of blood cells thathelp prevent/stop bleeding.

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What were the other results of this study?
How many participants had at least 50% reduction in AML after treatment?
In addition to the participants who showed complete response, an additional 12% (4 out of 34) ofparticipants in Part 1 and 9% (5 out of 56) of participants in Part 2 had at least 50% reduction in AML aftertreatment.

What were the participants’ condition and life duration after initial response toPLX3397 treatment?
Researchers further monitored participants who either had a complete response to treatment or at least
50% reduction in AML and measured how long it took for AML to return or get worse. Researchers also
recorded the length of time participants lived since they started treatment with PLX3397.
The results presented below show the amount of time it took about half of the participants to reach each of
the timepoints. This means that for half of the participants, it took less time and for the other half ofparticipants, it took more time.

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 side

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effects related to the study treatment PLX3397. The website listed at the end of this summary 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.

How many participants had serious side effects?
In this study, serious side effects were monitored for 34 participants in Part 1 and 56 participants in Part 2 who
took PLX3397.

In both Part 1 and Part 2, the most frequently reported serious side effect was of abnormally low number ofneutrophils accompanied with fever. Neutrophils are a type of white blood cells that help fight infections.
Other common serious side effects reported by participants are presented below.

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What were the most common side effects?
The most common side effects, both serious and non-serious, reported by at least 15% (15 out of 100) ofparticipants in any group are reported below.

PLX108-05 Clinical Results Summary | 9How many participants had to stop treatment because of side effects?
In Part 1, 2 participants stopped treatment due to abnormally low number of neutrophils accompanied withfever. Neutrophils are a type of white blood cells that help fight infections.
In Part 2, 2 participants stopped treatment, one due to abnormally low number of neutrophils accompaniedwith fever and the other due to a rash with raised red bumps on the skin.

How was this study useful for patients and researchers?
This study helped researchers learn about how participants with returning or treatment-resistant AML positive
for FLT3-ITD mutation respond to PLX3397 treatment. Findings from this study may be used to seek approval
to use study treatment in patients with AML who have an FLT3-ITD mutation. Other studies for PLX3397 areongoing.
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.

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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 NCT01349049 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 your study
site.
Full study title: A Phase 1/2 Safety and Efficacy
Study of Orally Administered PLX3397 in Adults
With Relapsed or Refractory Flt3-ITD-positive
Acute Myeloid Leukemia

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: 02 October 2020

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

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