Clinical Results Summary
A clinical study to learn about the safety and effects of quizartinib inpeople with a type of blood cancer called relapsed or refractory acute
myeloid leukemia
Protocol number: CP0001

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 researchfor people affected with a type of blood cancer called relapsed or refractory 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.

CP0001 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:•

did not respond to their first cycle of treatment (known as refractory AML); or•

did respond and were free of disease but then their AML came back after receiving at least the firstcycle of treatment (known as relapsed AML); orwere not suitable to receive initial (first) chemotherapy treatment due to their age, health status orother reasons, according to the researcher’s judgment.
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.
•At this time, the main treatment option for AML is chemotherapy. Chemotherapy uses medicines to kill cancer
cells or stop them from growing and dividing. You can have chemotherapy through a drip into a vein, as atablet you swallow or by an injection under the skin. People with AML might also have a procedure called astem cell transplant, which attempts to remove the cancerous blood forming cells from the bone marrow andreplace them with healthy cells taken, in most of the cases, from another healthy person (donor). The newcells can now multiply and produce healthy cells.
In this study, researchers wanted to learn more about the safety and effects of quizartinib in AML patients.

Treatment given in this study

CP0001 Clinical Results Summary | 2

Main purpose of this study

The main questions the researchers wanted to answer in this study were:

Other purpose of this study

Researchers also wanted to answer the following questions:•What was the best response the AML participants had to treatment with quizartinib?

Best response could be either Composite complete remission (CRc) or Partial remission (PR).
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 inpreventing/stopping bleeding.
Partial remission was defined as disappearance of at least 50% of their blood cancer cells after treatment.
CP0001 Clinical Results Summary | 3

How long did participants live with their cancer before it got worse or the patient died due to any cause ofdeath? This is also called ‘Progression Free Survival’.
There were some additional questions that researchers wanted to answer but these are not discussed in thissummary.

•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 didn’t have any serious sideeffects. A serious side effect could have caused aparticipant to discontinue their treatment withquizartinib. The first participant was enrolled in thestudy in March 2007.
The results were collected up to February 2012 and a study report was created. This summary is based on thatreport.

Who was in this study?
This study included a total of 76 participants from 2 countries: 57 from the United States and 19 from Georgia.
Participants could take part in this study if they:•were diagnosed with AML,

•were at least 18 years old,

•did not respond to their first treatment, or did
respond and were free of disease but then their AML
came back after receiving their first treatment, or•were never treated as they were not able to betreated with induction chemotherapy because of
their age, health status or other reasons,•

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, OR able to manage limited self-care and be out of bed for less than 50 % of waking hours,•

did not have another type of blood cancer, specifically acute promyelocytic leukemia,
CP0001 Clinical Results Summary | 4

•

did not have severe side effects from prior chemotherapy or surgery,•did not have surgery or radiation therapy within 4 weeks before participating in the study,•

did not have any major heart problems such as heart failure within 3 months before participating in thestudy,•

did not have hepatitis B or C, or Human Immunodeficiency Virus (HIV), and•did not have bone marrow transplant within 2 months before the study.

What happened during this study?
This was a Phase 1 study. Phase 1 studies are done to find out how a new study treatment works in a small
number of participants. This helps researchers understand what happens to the study treatment in the body,and if there are any side effects.
This was an “open label” study. This means that the study doctors, the participants and the researchers knew
what treatment was given. All participants took quizartinib as an oral solution. They continued to receive
quizartinib as long as they benefited from the treatment without any serious side effects.
Researchers started by giving participants 12milligrams (mg) of quizartinib. Once the researchers considered
this dose of quizartinib safe, the next group of participants received a higher dose of quizartinib. This process
was repeated with increasingly higher doses, until researchers identified the highest dose of quizartinib that
could safely be given to participants.
When the study started, participants took quizartinib daily for 14 continuous days, followed by 14 days of rest
(1 cycle of 28 days). This dosing regimen was called intermittent dosing (ID). The ID doses levels studied
ranged from 12 mg to 450 mg per dosing day.
While the study was ongoing, the dosing regimen was changed. New participants entering the study at thatpoint took quizartinib daily for 28 days (1 cycle) with no breaks between cycles. This dosing regimen was called
continuous dosing (CD). The CD doses levels studied were 200 and 300 mg/day. The researchers identified
200 mg/day CD as the highest dose of quizartinib that could safely be given to participants.
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.

CP0001 Clinical Results Summary | 5

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.

Side effects are medical problems (this may range from something mild such as a feeling tired or something
more severe like a severe infection or other medical problem) that happened during the study, which thestudy doctor (investigator) thought could be related to the treatments in the study. Detailed information
about side effects reported by participants is presented in the section ‘What side effects did the participants
developed during the study?’
During the study, 39 (51%) out of 76 participants had side effects.

CP0001 Clinical Results Summary | 6

To answer this question, researchers took blood samples from participants in each group on Day 1 and Day 8of treatment with quizartinib. They measured the highest level of quizartinib in the participants’ blood on
Day 1 and Day 8 of treatment. However, the results of this measurement were unreliable.

What were the other results of this study?
What was the best response the AML participants had to treatment withquizartinib?
Best response could be either Composite complete remission or Partial remission.
To answer this question, researchers checked how many AML participants had composite complete remission
or partial remission. The definitions of these terms can be found on Pages 2 and 3 of this document.
Overall, 30% (23 out of 76) of participants showed composite complete remission or partial remission
after treatment with quizartinib during the study.

13% (10 out of 76) of participants had composite complete remission to treatment with quizartinib.
•••

3% (2 out of 76) of participants had complete remission.
4% (3 out of 76) of participants had complete remission with incomplete platelet recovery.
7% (5 out of 76) of participants had complete remission with incomplete hematologicalrecovery.

17% (13 out of 76) of participants had partial remission after treatment with quizartinib.
How long did participants live with their cancer before it got worse or led todeath?
For half of the participants, it took at least 9 weeks (2 months) for their cancer to start getting worse or to leadto death.
CP0001 Clinical Results Summary | 7How long did the participants receive treatment during the trial?
The median duration for which the participants received different doses of quizartinib during the trial ispresented below. Median means the midpoint value for a group. For example, in the group of participants
who were treated with 12 mg quizartinib, the duration of the treatment for half of them was less than 14 days
and for the other half it was more.

What side effects did the participants developed 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 lastingproblems, 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.

CP0001 Clinical Results Summary | 8

How many participants had serious side effects?
During the study 6 (8 %) out of 76 participants had serious side effects. Serious side effects reported byparticipants were:

No death was reported due to side effects.

CP0001 Clinical Results Summary | 9How many participants had side effects?

The most common side effects, both serious and non-serious, that occurred in at least 10% (10 out of 100) ofparticipants were:How many participants had to stop treatment because of side effects?

The most common side effects that caused participants to stop quizartinib treatment were changes inelectrical activity in the heart (Electrocardiogram QT prolonged) and bleeding in the stomach.

How was this study useful for patients and researchers?
This study helped researchers to learn about the safety and effects of quizartinib in people with AML tested
negative or positive for FLT3-ITD alteration (or mutation). Based on the results of this study, researchers
identified 200 mg/day CD as the maximum dose of quizartinib that could safely be given to patients in furtherstudies.

CP0001 Clinical Results Summary | 10

Findings from this study may be used in other studies to learn whether patients with AML are helped by thistreatment. Other studies for 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 website:www.clinicaltrials.gov: Use the NCT identifier NCT00462761 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 1 Open-Label, Sequential Dose Escalation
Study Investigating the Safety, Tolerability,
Pharmacokinetics, and Pharmacodynamics ofAC220 when Administered Daily to Patients withRelapsed or Refractory 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 February 2021

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

CP0001 Clinical Results Summary | 11