Clinical Results Summary
A clinical study to learn about the safety of quizartinib in
combination with standard chemotherapy in people with a typeof blood cancer called acute myeloid leukemia
Protocol number: 2689-CL-0005

Thank You!

Daiichi Sankyo, Inc., the sponsor of this study, would like to thank the participants who
took part in this study for quizartinib, also known as AC220. Each participant helped toadvance medical research for people affected with a type of blood cancer, called newly
identified 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.

2689-CL-0005 Clinical Results Summary | 1

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 were newly diagnosed with AML and did not receive any
previous treatment for 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 normalblood 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 bloodstream 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 to stopthem from growing and dividing. You can have chemotherapy through a drip into a vein, as a tablet you
swallow, or by an injection under the skin. People with AML might also have a procedure called a stem celltransplant. This procedure removes the cancerous blood-forming cells from the bone marrow and replaces
them with healthy cells taken, in most of the cases, from another healthy person (donor). The new cells canmultiply and produce healthy cells.
People with AML may or may not have certain gene alterations (or mutations). People with FLT3-ITD positive
AML have an alteration (or mutation) in the FLT3 gene. FLT3-ITD positive AML is often severe, does not
respond well to treatment, and is likely to come back even after treatment. Quizartinib is designed to workagainst AML cells with this genetic mutation.
In this Phase 1 study, researchers wanted to see how safe quizartinib was at treating people newly diagnosed
with FLT3-ITD positive or negative AML when given along with the standard chemotherapy. Phase 1 studies
are done to find out the safety of a new study treatment, how it works, and what happens to the study
treatment in the body of a a small number of participants.

2689-CL-0005 Clinical Results Summary | 2

Treatments given in this study

Main purposes of this study

The main questions the researchers wanted to answer in this study were:How long was this study?
This study was designed in such a way that the participants
could continue to take quizartinib as long as they did notmeet certain criteria for discontinuing treatment.
The first participant entered the study in November 2011.
The sponsor ended this study early for administrative andresource issues which were not related to any safety oreffects of quizartinib.
The study ended in July 2013 and a study report was created. This summary is based on that report.
2689-CL-0005 Clinical Results Summary | 3

Who was in this study?
This study included 19 participants from the United States.
Participants could take part in this study if they:•

were 18 to 60 years old,•

were newly diagnosed with AML,•

did not receive any previous treatment forAML,•

had normal kidney, liver, and blood clotting
parameters, and•were fully active, OR unable to do hard
physical activity but able to walk and do lighthousework or office work, OR unable to work
but able to walk and manage selfcare and be out of bed for more than 50% of waking hours.

What happened during this study?
This study was “open label”. This means that both the researchers and the participants knew which treatment
was given to which participants. Participants took quizartinib oral solution along with standard chemotherapy
as an injection. The study treatment was given to participants in 2 phases: the induction phase followed by theconsolidation phase.

Induction phase

The aim of the induction phase is to clear the participants’ blood of AML. In the induction phase, quizartinib
was given with standard chemotherapy (daunorubicin and cytarabine) for up to 2 cycles. Participants took
quizartinib tablets once every day for 7 or 14 days during 1 cycle of treatment (which lasted 42 days). The
participants who showed either complete remission (CR) or complete remission with incomplete
hematological recovery (CRi) at the end of the induction phase could proceed to the consolidation phase.
CR and CRi were defined as:•Complete remission which is also called “CR”: CR meant less than 5% (5 out of 100) cells inparticipants’ bone marrow were cancer cells, with complete recovery of neutrophils and platelets*.
There were no signs of AML in the bone marrow or any parts of the body, and the participants’ blood
cells had recovered without the need of blood or platelet transfusion.
2689-CL-0005 Clinical Results Summary | 4•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, OR incomplete recovery of platelets. The participants may or may not have needed bloodor platelet transfusion.

*Neutrophils are a type of white blood cell that fights bacteria. Platelets are a type of blood cell that helps inpreventing/stopping bleeding.

Consolidation phase

The aim of the consolidation phase is to maintain the response the participant achieved at the end of theinduction phase. In the consolidation phase, participants took quizartinib tablets once every morning for 7 or
14 days during 1 cycle of treatment (which lasted 21 days). Quizartinib was given with standard chemotherapy(high-dose cytarabine) for up to 3 cycles or until participants could go on to receive a stem cell transplant.
Participants continued to the consolidation phase only if their blood cancer disappeared.
This study was divided into 2 parts.

Part 1

During Part 1, researchers started by giving participants 60 milligrams (mg) of quizartinib for 7 days (Group 1).
Once the researchers considered this dose of quizartinib safe, the next group of participants received 60 mg ofquizartinib for 14 days (Group 2). At this dose level and schedule (60 mg for 14 days), researchers noted somedose-limiting toxicities (DLTs), so the next group of participants received a lower dose of 40 mg for 14 days
(Group 3). This dose was identified as the highest dose of quizartinib that could be safely given to participants,
therefore it was selected for further research in Part 2 of the study.

Part 2

Part 2 of this study was planned to find out more about the safety and effects of the dose of quizartinib
selected during Part 1. However, the study was terminated before Part 2 could begin. Based on Part 1,
researchers decided that 40 mg dose for 14 days was the maximum dose to be taken in further plannedstudies.

2689-CL-0005 Clinical Results Summary | 5Researchers collected bone marrow and blood samples from the participants throughout the study to checkthe effect of quizartinib on AML. Researchers also monitored the health of the participants throughout thestudy.

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.

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. Detailed information about side effects
2689-CL-0005 Clinical Results Summary | 6reported by participants is presented in the section ‘What side effects did the participants develop during thestudy?’During the study, 79% (15 out of 19) participants had side effects.

The number of dose-limiting toxicities helped researchers decide whether the given dose of quizartinib incombination with standard chemotherapy was safe, and decide the dose of quizartinib that could be given to
the next group of participants.

2689-CL-0005 Clinical Results Summary | 7

What side effects did the study participants develop during thestudy?
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 are not reported here. For more information on
medical problems, please visit the websites listed at the end of this summary.

2689-CL-0005 Clinical Results Summary | 8

How long did the participants receive treatment during the study?
Participants in Group 2 were in the study longer than the participants in Group 1 or Group 3. The next figure
shows the median duration for which the participants in any of the groups received quizartinib. Median means
the midpoint value for a group. For example, for the participants in Group 1, the duration of the treatment forhalf of them was less than 7 days, and for the other half, it was more.

2689-CL-0005 Clinical Results Summary | 9How many participants had serious side effects?

In this study, side effects were monitored for 19 participants. A total of 16% (3 out of 19) participants hadserious side effects related to quizartinib.
•Group 1 (Quizartinib 60 mg for 7 days): 33% (2 out of 6) participants had serious side effects.
1 participant had a side effect of abnormally low number of neutrophils accompanied with fever. The
other participant had a side effect of liver infection.

•Group 2 (Quizartinib 60 mg for 14 days): None of the 7 participants in this group had serious sideeffects.

•

Group 3 (Quizartinib 40 mg for 14 days): 17% (1 out of 6) participants had serious side effects ofinflammation in the membrane/coat surrounding the heart and feeling sick to the stomach.

There were no deaths due to quizartinib.

How many participants had side effects?

Side effects reported, both serious and non-serious, are presented in this section.
79% (15 out of 19) of participants reported side effects related to quizartinib.

2689-CL-0005 Clinical Results Summary | 10

The most common side effects, which happened in at least 20% of the participants in any group, are presentedbelow.

How many participants had to stop treatment because of side effects?
Due to side effects, 11% (2 out of 19) of participants stopped treatment early. These were redness, swelling,and pain on the hands and feet which is associated with tingling sensation in Group 2 (Quizartinib 60 mg for14 days); and inflammation in the membrane/coat surrounding the heart and feeling sick to the stomach inGroup 3 (Quizartinib 40 mg for 14 days). The side effect of inflammation in the membrane/coat surrounding
the heart was a Dose-Limiting Toxicity.
2689-CL-0005 Clinical Results Summary | 11How was this study useful for patients and researchers?
This study helped researchers learn about a safe dose of quizartinib in patients with newly diagnosed AML
who had not received any previous treatment for AML.
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 NCT01390337 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: A Phase 1 Study of AC220 inCombination with Induction and Consolidation
Chemotherapy in Patients with Newly Diagnosed
Acute Myeloid Leukemia (AML)

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: 16 August 2021

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

2689-CL-0005 Clinical Results Summary | 12