Clinical Results Summary
A clinical study to learn about the safety and effects ofpexidartinib when given with pembrolizumab in people withadvanced skin cancer and other solid tumors
Protocol number: PLX108-14

Thank You!

Daiichi Sankyo, Inc., the sponsor of this study, would like to thank the participants who
took part in this study for pexidartinib, also known PLX3397, when given withpembrolizumab. Each participant helped to advance medical research for people whohave advanced skin cancer or other solid tumors. Their contribution to medicine andhealthcare 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?
Advanced melanoma and other solid tumors
Melanoma is a type of skin cancer in which tumors form when there is damage to melanin-producing cells.
Melanin is a natural skin pigment that gives a dark color to skin, hair, and eyes. Melanomas can develop
anywhere on the body. A solid tumor is a type of cancer or other abnormal growth that starts in an organ of
the body.
Cancers are considered “advanced” if the cancer
spreads to other parts of the body. Some people
may have advanced melanoma or solid tumors thateither do not respond to any of the treatments listed
in the blue box on the right or come back after being
treated. Therefore, new methods for treating
advanced cancers are needed.
Pexidartinib, also known as PLX3397, is being tested
for its ability to reduce the growth of cancer cells. Pembrolizumab is an anti-cancer treatment which
stimulates body’s immune system to fight cancer cells. The immune system includes organs and processes ofthe body that provide resistance to infection and toxins. In this study, researchers wanted to understand thesafety and effect of pexidartinib when given with pembrolizumab in participants with advanced melanoma
and solid tumors.
This study had 2 parts. In Part 1, participants with any type of advanced solid tumor could enter. Part 2 wasplanned to include participants with advanced melanoma and selected advanced solid tumors (see page 7and 8 for more details).

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Treatments given in this study

Main goal of this study
The main question the researchers wanted to answer in this study was:Other goal of this study
Researchers also wanted to answer the following question:•How many participants had tumors that completely disappeared or became at least 30% smaller aftertreatment with pexidartinib in addition to pembrolizumab?

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How long was this study?
The study was designed in such a way that theparticipants could continue study treatment for up to2 years as long as their cancer did not get worse andthey did not have serious side effects.
The study started in July 2015 and was stopped early, inOctober 2018, because after Part 1 was completed,researchers could not find enough evidence that study
treatment benefited the participants. By this time, 45 participants had already been enrolled in Part°2 of thestudy. The results were collected up to December 2017 for the study report. This summary is based on thatreport.

Who was in this study?
This study included 78 participants from 13 sites in the United States.
Participants could take part in this study if they:•were 18 years of age or older•

had cancer that had re-occurred, spread to other parts of the body, did not respond to treatment, orfor which no treatment was available•

were either fully active or unable to do a hard physical activity but able to walk and do light work

Part 1: had any type of advanced solid tumors
Part 2: had any one of the following tumor types:•

non-small cell lung cancer: a type of lung cancer•

squamous cell cancer of the head and neck: cancer that occurs in the outermost surface of the skinor certain tissues within the head and neck region including throat, mouth, sinuses and nose•

melanoma: skin cancer•

ovarian cancer: cancer of the ovaries (female organs that produce eggs)•

renal cell carcinoma: kidney cancer•

grade 4 glioblastoma: cancer of brain or spine which has spread to other parts of the body•gastro-intestinal stromal tumor: stomach cancer
PLX108-14 Clinical Results Summary | 4•triple-negative breast cancer: breast cancer•

pancreatic ductal adenocarcinoma: cancer of pancreatic duct (parts lying behind the lower part ofthe stomach)•gastric cancer: stomach cancer•high grade soft tissue sarcoma: cancer that begins in tissues, like muscles, tendon, fat, lymph andblood vessels, and nerves and is quickly spreading•

cholangiocarcinoma: cancer of the bile duct (tube that carries bile, the digestive fluid made by theliver between liver and gallbladder and the small intestine).

Part 2 was planned to include participants with any of the above tumor types. Following completion of Part 1,
the sponsor decided to limit enrollment in Part 2 of the study to the following 5 types of cancer: melanoma,
non-small cell lung cancer, ovarian cancer, squamous cell cancer of head and neck, and gastro-intestinal
stromal tumor.

What happened during this study?
This was a Phase 1 and 2a study. Phase 1 studies are done to find the highest dose of a drug that can be safely
given to participants who are receiving other therapy. Phase 2a studies are done to better understand if adrug can treat the condition it has been developed for.
This was an open-label study, which means that both the researchers and the participants knew which
treatment was given to which participant.
Participants first completed a screening period to find out if they could take part in the study.

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Part 1
Part 1 of this study was done to find the highest dose of pexidartinib that could safely be given to participantsin addition to 200 milligrams (mg) pembrolizumab. All participants received pexidartinib capsules by mouth
every day and pembrolizumab 200 mg infusion into the vein every 3 weeks.
The researchers started by giving 600 mg of pexidartinib, to the first group of participants. If this dose wasconsidered to be safe by the researchers, the next group of participants received a higher dose of pexidartinib.
If this dose was considered not to be safe by the researchers, the next group of participants received a lower
dose of pexidartinib. This process was repeated with increasingly higher doses until the highest dose that
could safely be given was identified.
For all groups, pexidartinib was given by mouth as two divided doses, one in the morning and one in theevening each day.
The researchers identified 600 mg pexidartinib as the highest dose in Part 1 that could safely be given toparticipants. The different treatment groups are shown in the figure below.

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Part 2In Part 2, researchers gave the highest recommended dose of pexidartinib (600 mg) in addition to 200 mg
pembrolizumab to participants with advanced melanoma and selected advanced solid tumors to find out if
this combination was beneficial for them. In Part 2, 45 participants were divided into following 5 groups basedon the cancer type they had:•melanoma: 13 participants•

non-small cell lung cancer: 8 participants•

ovarian cancer: 15 participants•squamous cell cancer of head and neck: 3 participants•

gastro-intestinal stromal tumor: 6 participants

All participants received pexidartinib 600 mg, capsules by mouth every day and pembrolizumab 200 mg
infusion into the vein every 3 weeks.
The participants in this study continued to receive the treatment for up to 2 years as long as they did not show
worsening of cancer, have serious side effects, or ask to be removed from the study.

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 side effects during this study?
Side effects are medical problems (such as a feeling tired) that happened during the study which the study
doctor thought could be related to the treatments in the study.
In this study, side effects were monitored for 78 participants in Part 1 and 2.

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More detailed information about the side effects reported by participants is given below in the “MedicalProblems” section of this summary.

What were the other results of this study?
How many participants had tumors that completely disappeared or became 30%
smaller after treatment with pexidartinib in addition to pembrolizumab?

In Part 1, out of the 2 participants who had at least 30% reduction in tumor size:• 1 participant received 600 mg per day of pexidartinib and had cancer that had spread to liver and• 1 participant received 800 mg per day of pexidartinib and had cancer that had not spread to liver
In Part 2, 3 participants who had at least 30% reduction in tumor size and received 600 mg per day dose ofpexidartinib:• 2 participants had melanoma and• 1 participant had ovarian cancer

PLX108-14 Clinical Results Summary | 8What medical problems did the study participants have?
This section provides a summary of side effects related to pexidartinib. The website listed at the end of thissummary 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?

There were no deaths reported in this study that were considered to be related topexidartinib.
PLX108-14 Clinical Results Summary | 9How many participants had most common side effects?
The most common side effects related to pexidartinib, both serious and non-serious, that occurred in at least
33% (33 out of 100) of participants in any group are reported below.

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PLX108-14 Clinical Results Summary | 11How many participants had to stop treatment because of side effects?

In part 1, the participant stopped taking pexidartinib due to side effects of liver function test outside normal
range.
In part 2, the side effects that led to participants’ stopping pexidartinib were increase in liver test values ofalanine aminotransferase, aspartate aminotransferase, and transaminases, and feeling tired.

How was this study useful for patients and researchers?
This study helped researchers learn about the safety and effects of pexidartinib when given in addition topembrolizumab in patients with skin cancer and other solid tumors. The study was stopped early because
researchers could not find enough evidence that the study treatment benefited the participants.
Findings from this study may be used in other studies to learn whether patients with advanced melanoma andother solid tumors are helped by this treatment. Other studies for pexidartinib 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.

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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 NCT02452424 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:

Sponsor: Daiichi Sankyo, Inc.

Phase 1/2a Study of Double-immune Suppression
Blockade by Combining a CSF1R Inhibitor(PLX3397) with an Anti-PD-1 Antibody(Pembrolizumab) to Treat Advanced Melanoma
and Other Solid Tumors

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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