Clinical Results Summary
A clinical study to learn about the effects and safety of two doses of
quizartinib in people with a type of blood cancer called relapsed or
refractory acute myeloid leukemia
Protocol number: 2689-CL-2004

Thank You!

Daiichi Sankyo, Inc., the sponsor of this study, would like to thank the participants who
took part in this study for quizartinib. Each participant helped to advance medical
research and knowledge for people affected with a type of blood cancer called relapsed or
refractory acute myeloid leukemia. Their contribution to medicine and healthcare isgreatly 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?
Acute myeloid leukemia (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 FLT3-ITD positive refractory or relapsed AML that either:• did not respond to their second AML treatment (known as refractory AML), or• did respond and were free of disease but then their AML came back after their second AML treatment
or stem cell transplant (known as relapsed AML).
AML is a cancer of the blood and the bone marrow. The bone marrow is found in the center of most bones,
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, so there are fewer healthy blood cells.
These cancerous cells can also enter the blood stream and circulate in the blood, and go to different parts ofthe body.
The main treatment for AML is chemotherapy. Chemotherapy uses medicines to kill cancer cells or stop themfrom growing and dividing. You can have chemotherapy through a drip into a vein, as a tablet you swallow orby an injection under the skin. People with AML might also have a procedure called a stem cell transplant,
which attempts to remove the cancerous blood forming cells from the bone marrow and replace them withhealthy cells taken, in most of the cases, from another healthy person (donor). The new cells can now multiply
and produce healthy cells.
People with AML can have certain gene alterations (or mutations). People with FLT3-ITD positive AML have analteration (or mutation) in the FLT3 gene. Participants in this study had FLT3-ITD positive AML. FLT3-ITD
positive AML participants had severe symptoms, they did not respond well to standard treatment, and their
AML was likely to come back even after treatment. Quizartinib is designed to work against AML cells with thisgenetic mutation. Researchers wanted to see how effective and safe quizartinib is at treating people withrefractory or relapsed FLT3-ITD positive AML.

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Treatment given in this study

Main purposes of this study
The main questions the researchers wanted to answer in this study were:Composite complete remission was defined as the sum of:•Complete remission, which is also called “CR”: CR meant less than 5% of cells in the participant’s bonemarrow were cancer cells, with complete recovery of neutrophils and platelets*. There were no signsof AML in the bone marrow or any parts of the body, and the participant’s blood cells had recovered
without the need of any transfusion; plus•

Complete remission with incomplete platelet recovery, which is also called “CRp”: CRp meant lessthan 5% of cells in the participant’s bone marrow were cancer cells, with incomplete recovery ofplatelets; plus•

Complete remission with incomplete hematological recovery, which is also called “CRi”: CRi meantless than 5% of cells in the participant’s bone marrow were cancer cells, with incomplete recovery ofneutrophils, with or without complete recovery of platelets. The participant may or may not haveneeded blood or platelet transfusion.

*Neutrophils are a type of white blood cells that fight bacteria. Platelets are a type of blood cells that help in preventing/stopping
bleeding.

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Other purposes of this study

Researchers also wanted to answer the following questions:•

How long did AML participants live after initiating treatment with quizartinib until they died due to any
cause? This is also called ‘Overall Survival’.

•

For participants who achieved composite complete remission or partial remission* to quizartinib
treatment, how long did the effect last? This is also called ‘Duration of Remission’.

• What side effects did the participants develop during the study?
There were some additional questions that researchers wanted to answer but these are not discussed in thissummary.
*Partial remission was defined as disappearance of at least 50% of the participant’s blood cancer cells after treatment.

How long was this study?
The study was designed in such a way that theparticipants could continue in it as long as they
benefited from the treatment and their AML did not
get worse, and they did not have any serious side
effects. A serious side effect could have caused aparticipant to discontinue their treatment withquizartinib.
The study was completed as planned. The study started in May 2012 and ended in March 2015 and a study
report was created. This summary is based on that report.

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Who was in this study?
This study included 76 participants from the following 4 countries:

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Participants could take part in this study if they:•

were diagnosed with AML or myelodysplastic
syndrome (another type of blood cancer) that
progressed to AML,•

tested positive for the FLT3-ITD mutation,•

were aged 18 years or older,•

did not respond to their second AML treatment,
or did respond and were free of disease but then
their AML came back after receiving their second
AML treatment or stem cell transplant,•

were fully active, OR unable to do hard physical activity but able to walk and do light housework or
office work, OR unable to work but able to walk and manage self-care and be out of bed for more than
50% of waking hours,•

did not have any major heart problems such as an irregular heart rhythm or family history of the sameor chest pain,•

did not have any other diseases or abnormal laboratory tests that could prevent them from attending
study visits and assessments.

What happened during this study?
This was a Phase 2 study. In Phase 2 studies, the study treatment is given to a small number of participants withthe disease condition to gather information about the effects of the study treatment.
This study was “open label”. This means that both the researchers and the participants knew what treatment
was given to which participants.
Participants were screened to find out if they could take part in the study.
Researchers used a computer system to assign participants into two groups by a process called randomization.
The system was designed to ensure that participants were equally divided into two groups:•

Group 1: participants received a starting dose of 30 milligrams/day (mg/day) of quizartinib•

Group 2: participants received a starting dose of 60 mg/day of quizartinib.

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Participants took quizartinib oral solution once every morning for 28 days. This cycle of treatment could be
repeated for as long as they benefited from the treatment without any serious side effects.
The 30 mg/day dose could be increased to 60 mg/day and the 60 mg/day dose could be increased to
90 mg/day in participants with no response or whose cancer came back.
Researchers collected bone marrow and blood samples from the participants throughout the study to checkthe effect of quizartinib on AML. They also monitored the health of the participants throughout the study.
During the long term follow-up, the participants well-being and further AML treatment were checked via aphone call every 3 months.

What were the key results of this study?
Key results from this study are shown for each group of participants collectively. This summary does not show
the results from each individual participant. An individual participant’s results could be different from the total
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group of participants. A full list of the questions the researchers wanted to answer and a detailed presentationof the results can be found on the websites listed at the end of this summary.

To answer this question, researchers measured the heart’s electrical activity of each participant during thestudy using a simple test called electrocardiogram (ECG). This test measures disruptions in the heart’s
electrical activity. Researchers calculated how many participants had disruptions in their heart’s electricalactivity. Researchers then categorized the participants into different levels based on their recorded value inmilliseconds (msec).
Researchers reported abnormal changes in the electrical activity of heart of 2 subjects in the 60 mg/day groupas serious side effects. Please refer to the section ‘How many participants had serious side effects?’ onPage 11.

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Percentage of participants who showed abnormal changes in the electrical activity of heart(Electrocardiogram QT prolonged) after treatment with quizartinib

Level of change in theelectrical activity of heart

Quizartinib(30 mg/day)Quizartinib(60 mg/day)Level 1
Mild
between 450 and 480 msec

42%
(16 out of 38 participants )47%(17 out of 36 participants)

Level 2Moderate
between 480 and 500 msec

5%
(2 out of 38 participants )14%(5 out of 36 participants)

Level 3Severemore than 500 msec

5%
(2 out of 38 participants )3%(1 out of 36 participants)

What were the other results of this study?
How long did AML participants live after initiating treatment with quizartinib
until they died due to any cause?

Researchers measured the time from starting the treatment until the participants died due to cancer or any
other cause. At the end of this study, researchers found that:•about half of the participants who started quizartinib at the 30 mg/day dose lived for at least 21 weeks,
and•about half of the participants who started quizartinib at the 60 mg/day dose lived for at least 27 weeks.

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For participants who achieved composite complete remission or partial
remission to quizartinib treatment, how long did the effect last?
Researchers measured the time from the participants’ first response to study treatment which included either
composite complete remission or partial remission until their cancer came back. The definitions of these terms
can be found on Pages 3 and 4 of this document.
Researchers found that:•about half of the participants who achieved composite complete remission at the initial 30 mg/day
dose, the effect lasted for at least 4 weeks, and•about half of the participants who achieved composite complete remission at the initial 60 mg/day
dose, the effect lasted for at least 9 weeks;•

about half of the participants who achieved either composite complete remission or partial remission
at the initial 30 mg/day dose, the effect lasted for at least 7 weeks, and•about half of the participants who achieved either composite complete remission or partial remission
at the initial 60 mg/day dose, the effect lasted for at least 9 weeks.

How long did the participants receive treatment during the trial?
The participants who took the quizartinib 60 mg/day starting dose were in the study longer than theparticipants who took the quizartinb 30 mg/day starting dose. The next figure shows the median duration forwhich the participants received treatment. Median means the midpoint value for a group. For example, in thegroup of the participants who were treated with the quizartinib 30 mg/day starting dose, the duration of thetreatment for half of them was less than 66 days, and for the other half it was more.

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What side effects did the participants develop during the study?
Side effects are medical problems (this may range from something mild such as feeling tired or something
more severe like a severe infection or other medical problem) that happened during the study, which thestudy doctor thought could be related to the treatments in the study.
Side effects are considered serious if they cause death, are life-threatening, cause disability, cause lasting
problems, cause birth defects, or require hospitalization. Some participants stopped study treatment becauseof side effects.
Side effects other than those related to study treatment (quizartinib) are not reported here. For more
information on medical problems, please visit the websites listed at the end of this summary.

How many participants had serious side effects reported as related toquizartinib?

The percentage and number of participants in each group who reported at least one serious side effect related
to quizartinib were:2689-CL-2004 Clinical Results Summary | 11

The serious side effects that occurred during the study were:2689-CL-2004 Clinical Results Summary | 12

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How many participants had side effects reported as related to quizartinib?
Side effects reported, both serious and non-serious, that were related to quizartinib are presented in thissection.

The most common side effects that occurred in at least 10% (10 out of 100) of participants in any group were:2689-CL-2004 Clinical Results Summary | 14

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

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How was this study useful for patients and researchers?
This study helped researchers to learn about the effects and safety of quizartinib in people with relapsed or
refractory AML. Based on the results of this study, researchers decided that 60 mg was the maximum dose to
be taken forward into further studies.
Findings from this study may be used in other studies to learn whether patients with AML are helped by thistreatment. Other studies on quizartinib 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 NCT01565668 in the search field.
https://www.clinicaltrialsregister.eu/ctr-search/search: Use the EudraCT identifier 2011-005408-13 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:

Sponsor: Daiichi Sankyo, Inc.

A Phase 2, Randomized, Open Label Study of the
Safety and Efficacy of Two Doses of Quizartinib(AC220; ASP 2689) in Subjects with FLT3-ITD
Positive Relapsed or Refractory Acute Myeloid
Leukemia (AML).

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: 25 March 2021

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