Clinical trial NCT05191797
Conditions: Extensive Stage Lung Small Cell Carcinoma Limited Stage Lung Small Cell Carcinoma
Keywords: Lung
Sponsor: University of Washington
Start date: 2022-04-11; Completion date: 2024-04-05
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase I/II trial studies the side effects of bomedemstat and maintenance immunotherapy with atezolizumab and to see how well they work in treating patients with newly diagnosed extensive stage small cell lung cancer. Bomedemstat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving bomedemstat and atezolizumab may work better in treating patients with extensive stage small cell lung cancer.

Detailed description:
OUTLINE:

Patients receive bomedemstat orally (PO) once daily (QD) on days 1-21 and atezolizumab intravenously (IV) on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter.

Arms: arm 1: Patients receive bomedemstat PO QD on days 1-21 and atezolizumab IV on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Bomedemstat intervention 2: Atezolizumab
Intervention descriptions: intervention 1: Given PO intervention 2: Given IV

Protocol documents:
ICF_000.pdf: 
 
 
Official Title: 
A PHASE I/II STUDY OF BOMEDEMSTAT COMBINED WITH 
MAINTENANCE IMMUNOTHERAPY FOR PATIENTS WITH 
NEWLY DIAGNOSED EXTENSIVE STAGE SMALL CELL LUNG 
CANCER (ES-SCLC) 
NCT Number: 
NCT05191797 
Document Type:  
Informed Consent Form 
Date of the 
Document: 
01/06/2023 
 
 


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Fred Hutchinson Cancer Center 
University of Washington Medical Center 
Consent to take part in a research study: 
 
A PHASE I/II STUDY OF BOMEDEMSTAT COMBINED WITH MAINTENANCE 
IMMUNOTHERAPY FOR PATIENTS WITH NEWLY DIAGNOSED EXTENSIVE STAGE 
SMALL CELL LUNG CANCER (ES-SCLC) 
 
Principal Investigator: Rafael Santana-Davila, MD. University of Washington.  
Fred Hutchinson Cancer Center. Telephone: 206-606-2190 
 
Sub-Investigators: Christina Baik, MD, Keith Eaton, MD, PhD, Joseph Hiatt, MD, 
PhD, Sylvia Lee, MD, Cristina Merkhofer, MD, Cristina Rodriguez, MD, Nicolas 
Giustini, MD , Diane Tseng, MD, PhD 
Emergency number (24 hours): 206-598-6190 
 
Important things to know about this study 
You are being asked to participate in this clinical research study because you have Small 
Cell Lung Cancer (SCLC). We are looking to enroll approximately 34 patients over the 
duration of this study expected to last 24 months. 
Research is not the same as treatment or medical care. The purpose of a research study 
is to answer scientific questions.   
Your participation in this study is voluntary, which means you can choose whether you 
want to participate.  If you decide to participate and later change your mind, you are free 
to stop participation at any time.  This consent form was created to help explain to you 
the nature of the study and if you choose to participate, it will be used to document your 
agreement to be part of this study. 
Please read the following informed consent form to learn about what will happen if you 
agree to take part in this research study.  This consent form may contain some words 
that you do not understand.  Please ask your study doctor or someone from the study 
staff to explain any words or information that you do not clearly understand.  This consent 
form will give you detailed information about this study.  Please ask the study staff as 
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many questions as you need before you decide if you want to be in the study.  You may 
also want to take home an unsigned copy of this consent form to discuss this study with 
friends and family before making your decision. 
We do not know if bomedemstat will help you, and it could even make your 
condition/disease worse. Bomedemstat could cause side effects such as those 
described below in this form.  
You can choose to receive standard methods for your disease instead of participating in 
this study. We will give you details about the purposes, procedures, risks and possible 
benefits related to this study. We will explain other choices that you have. We will also 
give you any other information that you need to make an informed decision about joining 
this study. 
After you are sure that you clearly understand the risks and benefits of taking part in this 
study, if you choose to take part in the study, you will be asked to sign this consent form.  
You should not sign this consent form if you have any questions that have not been 
answered.  By signing this consent form, you are confirming that the study has been 
explained to you, and that you give your permission to be a part of the study. 
Following is a more complete description of this study. Please read this description 
carefully. You can ask any questions you want to help you decide whether to join the 
study. If you join this study, we will give you a signed copy of this form to keep for future 
reference. 
Why are we doing this study? 
The purpose of this research is to learn about the safety of an investigational drug called 
IMG-7289 (also referred to as bomedemstat), and how well it is tolerated. It is considered 
investigational, which means that it has not been approved by the U.S. Food and Drug 
Administration (FDA). 
Imago BioSciences, Inc. is the manufacturer of bomedemstat and is providing the study 
drug for this clinical research study.  
What research tests, procedures, and treatments are done in this study? 
Trial Treatments 
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• Atezolizumab administered on Day 1 of every cycle 
• bomedemstat capsules taken daily 
o Once a day, at the same time of day, at night before bed. 
o On an empty stomach. This means not eating food for 1 hour before 
taking your bomedemstat and for 30 minutes after.  
o By swallowing the capsules whole (do not chew or break them), with a 
glass of water.  
o You may drink clear liquids at any time before and after taking it. 
 
If you join this study, we would do the following tests and procedures: 
 
Screening Period 
The following assessments will be performed up to 28 days prior to start of study 
treatment: 
• Request for Archival tissue (tissue from a previous biopsy) if available. You may 
still participate if you do not have any remaining tissue from a previous biopsy. 
• Full Physical Examination 
• Vital Signs and Weight 
• Determine your performance status (ECOG) 
• Pregnancy test for females of childbearing age (within 72 hours of starting 
therapy) 
• A small amount of your blood (between 2-3 tablespoons) will be taken within 10 
days of starting therapy 
• Tumor imaging (MRI/CT scan) 
 
Treatment Period  
The following assessments will be performed on day 1 (+/- 3 days) of each treatment 
cycle and must be performed no more than 24 hours prior to treatment unless 
otherwise specified.  The only exception is for the screening period labs which will 
serve as baseline assessments and can be performed up to 3 weeks prior or as 
otherwise specified. 
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Day 1 of each new cycle 
• Adverse event review 
• Physical examination 
• Vital signs and weight 
• Performance status 
• A small amount of your blood (between 2-3 tablespoons) will be taken  
• Tumor Assessments (CT scan done every 8 weeks) 
 
Day 8 and Day 15 of each new cycle 
• A small amount of your blood (between 2-3 tablespoons) will be taken  
 
End of Treatment  
The End of Treatment Visit should be conducted at the time of permanent study 
treatment discontinuation, or within 7 days thereafter. 
 
• Adverse event review 
• Physical examination 
• Vital signs and weight 
• Performance status 
• A small amount of your blood (between 2-3 tablespoons) will be taken 
 
Post-Treatment Visits 
 
Safety Follow-Up Visit 
The Safety Follow-Up Visit should be conducted approximately 30 days after the last 
dose of trial treatment or before the initiation of a new anti-cancer treatment, 
whichever comes first.    
 
Follow-up Visits 
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Subjects who discontinue trial treatment for a reason other than disease progression 
will move into the Follow-Up Phase and should be assessed every 8 weeks to monitor 
your disease status.    
 
Survival Follow-up 
Once you experience confirmed disease progression or start a new anti-cancer 
therapy, you will move into the survival follow-up phase and will be contacted by 
telephone every 12 weeks to assess for survival status until death, withdrawal of 
consent, or the end of the study, whichever occurs first. 
How long will I be in this study? 
The study is expected to last for 24 months. You will remain in the study as long as you 
continue to benefit without your disease getting worse (disease progression) or a reaction 
to the treatment (toxicity) 
Can I stop being in this study? 
• You do not have to join this study. You are free to say “yes” or “no”.  
• If you get sick or hurt in this study, you do not lose any of your legal rights to 
seek payment by signing this form. 
• During the study, we might learn new information that you need to know. For 
example, some information may affect your health or well-being. Other 
information might make you change your mind about being in this study. If we 
learn these kinds of information, we will tell you. 
• If you join this study, you will not have to stay in it. You could stop at any time 
(even before you start). Your regular medical care would not change. You 
would have no penalty for stopping, but it would be better not to join the study 
if you think that you would change your mind later.   
 
What are the possible side effects or risks? 
Possible risks associated with bomedemstat 
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Common side effects reported and decided by study doctors to have been possibly, 
probably, or definitely related to bomedemstat include: 
• Low platelet count (47%) 
• Nausea (35%) 
• Diarrhea (32%)  
• Altered taste (25%) 
• Low red blood cell level (22%) 
• Vomiting (21%) 
• Fatigue (15%) 
 
Rare but serious side effects decided by study doctors to have been possibly or 
probably related to bomedemstat that resulted in hospitalization have been reported.:  
• Fever with low white blood cell count (febrile neutropenia; 7%) 
• Gastrointestinal (GI) bleeding (2%) 
• Low platelet count or worsened low platelet count (2%) 
• Bruising (1%) 
• Irregular heart rhythm (1%) 
• Bleeding in the lungs (1%) 
• Worsening lung function (1%) 
• Painful spleen (1%) 
• Differentiation syndrome (severe headache, sudden fever, difficulty 
breathing, sudden weight gain; 1%) 
• Heart block (1%) 
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• Constipation (1%)  
• Heart failure (1%) 
• Fungal infection in the chest (1%) 
• Illness with fever (1%) 
• Headache (1%) 
• Rectal bleeding (1%) 
 
The event below (respiratory failure), which occurred in another study, resulted in the 
death of a patient. It was determined by the study doctor to have been possibly related 
to taking bomedemstat. The manufacturer of the drug in consultation with the study 
medical monitor and members of the study safety committee, concluded that an 
infection was more likely the cause of the respiratory failure, and decided this event 
was not related to bomedemstat.  
 
• Respiratory Failure (1%) 
 
Additional side effects have been reported by participants; however, these side effects 
are not included as they either occurred in less than 15% of participants or were 
decided by the study doctors to have been unrelated to bomedemstat. 
 
A decrease in the number of various blood cells including platelets (help your blood to 
clot), white blood cells (help fight infection) and red blood cells (carry oxygen to your 
body). are side effects of how bomedemstat works. If your platelets and red blood cells 
become too low, you can be given more by a transfusion. If your white blood cells 
become too low, your doctor will consider medicines that can help raise them. 
 
Possible risks associated with Atezolizumab 
Atezolizumab is part of standard treatment for many patients with your disease. 
However, like any medication, atezolizumab can have side effects.  
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Atezolizumab is designed to increase the number of immune system cells in your body 
that can fight cancer. These cells may cause inflammation within the tumor, as well as 
in normal tissue. Therefore, by receiving atezolizumab, you may develop a condition 
where there is inflammation against a part of your own body (an autoimmune 
condition). The side effects associated with atezolizumab are listed below. There may 
be side effects that are not known at this time.  
Very common (occurs in more than 10% of subjects) 
•  Fatigue 
• Joint pain (arthralgia) 
• Lack of energy (asthenia) 
• Decreased appetite 
• Diarrhea 
• Urinary tract infection 
• Shortness of breath (dyspnea) Cough 
• Itching of the skin 
• Nausea 
• Fever 
• Rash 
• Vomiting 
• Muscle and bone pain (myalgia, musculoskeletal pain and bone pain) 
 
Common (occurs in 1%-10% of subjects) 
 
• Chills 
• Difficulty swallowing (dysphagia)  
• Increase in liver enzymes, which may indicate inflammation of the liver 
• Allergic reaction or intolerance to medication (hypersensitivity)  
• Decreased level of potassium in blood (hypokalemia)  
• Inflammation of the intestines (colitis) 
• Decreased oxygen supply in body resulting in shortness of breath (hypoxia) 
• Flu-like symptoms  
• Infusion-related reaction  
• Inflammation of the lungs (pneumonitis)  
• Low platelet count in the blood, which may make you more likely to bruise or 
bleed (thrombocytopenia)  
• Decreased level of sodium in blood (hyponatremia)  
• Low blood pressure (hypotension) 
• Underactive thyroid gland (hypothyroidism)  
• Nasal congestion 
• Stomach area pain (abdominal pain) 
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• Inflammation of the liver (hepatitis) 
 
Less common but important (occurs in less than 1% of subjects) 
 
• Decreased production of hormones by the adrenal glands (adrenal insufficiency) 
• Diabetes 
• Overactive thyroid gland (hyperthyroidism)  
• Inflammation of the brain and membrane surrounding the brain and spinal cord 
(meningoencephalitis) 
• Inflammation of the pituitary gland (hypophysitis) 
• Inflammation of the heart muscle (myocarditis) 
• Inflammation of the kidneys (nephritis) 
Nerve damage that may cause muscle weakness and/or paralysis (Guillain-Barré 
syndrome)  
• Nerve damage resulting in muscle weakness (myasthenic syndrome/myasthenia 
gravis) 
• Inflammation of the pancreas (pancreatitis)  
• Increase in pancreatic enzymes, which may indicate inflammation of the 
pancreas (increase in amylase and lipase) 
• Severe high levels of sugar and acids in the blood or urine (diabetic ketoacidosis) 
Inflammation or damage of the muscles (myositis) 
 
Among the side effects known to be associated with atezolizumab, your study doctors 
would like you to pay more attention to the following:  
• Inflammation of the intestines (colitis); symptoms may include diarrhea, blood in 
stool, and pain in stomach area 
• Inflammation of the thyroid glands (hypothyroidism, hyperthyroidism); symptoms 
may include headaches, fatigue, weight loss, weight gain, change in mood, hair 
loss, and constipation 
• Inflammation of the adrenal glands (adrenal insufficiency); symptoms may include 
dizziness, irritability, fainting, low blood pressure, skin darkening, and craving of 
salty foods 
• Inflammation of the pituitary gland (hypophysitis); symptoms may include fatigue 
and headaches that will not go away, increased thirst, increased urination, and 
changes in vision. Side effects that may occur at the same time include 
hypothyroidism and adrenal insufficiency (see above for details).  
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• Inflammation of the liver (hepatitis); symptoms may include yellowing of skin, pain 
in stomach area, nausea, vomiting, itching, fatigue, bleeding or bruising under the 
skin, and dark urine 
• Inflammation of the brain and membrane surrounding the brain and spinal cord 
(meningoencephalitis); symptoms may include neck stiffness, headache, fever, 
chills, vomiting, seizure, irritability, and eye sensitivity to light 
• Nerve damage resulting in muscle weakness (myasthenic syndrome/myasthenia 
gravis); symptoms may include weakness in the arm and leg muscles, double 
vision, and difficulties with speech and chewing 
• Nerve damage that may cause muscle weakness and/or paralysis (Guillain-Barré 
syndrome); symptoms may include tingling in fingers and toes, fatigue, and 
difficulty walking 
• Inflammation of the lungs (pneumonitis); symptoms may include new or worsening 
cough, shortness of breath, and chest pain 
• Inflammation of the heart muscle (myocarditis); symptoms may include shortness 
of breath, decreased exercise tolerance, fatigue, chest pain, swelling of the ankles 
or legs, irregular heartbeat, and fainting 
• Reactions associated with infusion (events occurring during or within 1 day of 
infusion); symptoms may include fever, chills, shortness of breath, and sudden 
reddening of the face, neck, or chest 
• Inflammation of the pancreas (pancreatitis); symptoms may include abdominal 
pain, nausea, vomiting, and fever 
• Condition of high levels of sugar in the blood (diabetes mellitus); symptoms may 
include increased thirst, increased hunger, frequent urination, irritability, and 
fatigue 
• Inflammation of the kidneys (nephritis); symptoms may include changes in urine 
output and color, pain in pelvis, and swelling of the body and may lead to failure of 
the kidneys 
• Inflammation or damage of the muscles (myositis, myopathies including 
rhabdomyolysis); symptoms may include muscle pain and weakness, urine with a 
dark brown or reddish color, nausea, and vomiting  
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Allergic Reactions 
Allergic reactions may occur with atezolizumab and typically occur while it is being given 
into your vein or shortly after it has been given.  Symptoms could include nausea, 
vomiting, skin reactions (hives or rash), difficulty breathing, or low blood pressure.  These 
reactions could be mild or severe and might lead to death or permanent disability.  If you 
experience any of these symptoms, your study doctor will interrupt, or even stop, the 
delivery of atezolizumab into your vein.  Your study doctor may also give you some drugs 
to treat these symptoms.   
 
Other Possible Risks 
Side Effects and Risks of Drawing Blood 
During this study, blood will be drawn to perform tests that allow your study doctors to 
see how you are doing.  Blood samples are obtained by inserting a needle into a vein.  
Drawing blood may cause pain where the needle is inserted, and there is a small risk of 
bruising, clotting, or, rarely, infection at the place where the needle is inserted.  Some 
people experience dizziness, upset stomach, or fainting when their blood is drawn. 
 
Radiation risks  
Magnetic Resonance Imaging (MRI)  
MRI scans use strong magnetic fields and radio waves to produce an image of the inside 
of the body. There are no known harmful effects from the strong magnetic field used in 
MRI scans. However, the magnet is so powerful that it can affect any unsecured metal 
objects, which can be pulled towards the magnet. The magnet may affect pacemakers, 
artificial limbs, and other medical devices or implants that contain metal. You should 
discuss any devices in your body with the study staff. You may feel some discomfort or 
anxiety when lying inside of the scanner. If you cannot have an MRI, you will have a CT.  
 
Computerized Tomography (CT-scan)  
A CT scan is a specialized x-ray test that takes images of the body. When a CT scan is 
performed, you will be exposed to radiation. Some of the tests that you will have in this 
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research study will expose you to radiation. Everyone receives a small amount of 
radiation every day called “background radiation”. This radiation is natural and comes 
from space, air, water, soil, and the food you eat. Each year you are exposed to about 3 
milliSieverts (mSv) of this background radiation. A milliSievert is a unit of radiation dose.  
 
For comparison, the estimated radiation dose from each CT scan performed in this the 
study is listed below: 
 
• CT-chest: 7mSv 
• CT-abdomen: 8 mSv 
• CT-pelvis: 6 mSv 
• CT-head: 2 mSv 
• CT-neck: 3 mSv 
 
The risk to your health from this level of radiation exposure is too low to be detectable 
and may be nonexistent. 
 
Reproductive risks  
The effects of the combination of bomedemstat and atezolizumab on an unborn child or 
newborn baby are not known. Because of this, it is important that study participants are 
not pregnant or breast-feeding and do not become pregnant during the study. You must 
not participate in the study if you are pregnant or trying to become pregnant, or breast-
feeding. If you are female and can have children, you will have a pregnancy test before 
starting study treatment. If you are male, you should not father a child or donate sperm 
for at least 1 month after the last dose of study medication. Both male and female 
participants must use effective contraception during the course of the study and for a 
period of 1 month after completion of the study. Your study doctor will discuss methods 
of effective contraception with you.  
 
 
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For female participants - if you do become pregnant while participating in the study, you 
should tell the study doctor immediately. Your study doctor will withdraw you from the 
study and advise on further medical attention should this be necessary. You must not 
continue in the study if you become pregnant. We will ask you to sign a separate consent 
and plan on following you during your pregnancy until outcome. 
 
 
For male participants - you should tell the study doctor if you father a child while 
participating in the study. We will ask your partner to sign a separate consent and plan 
on following them during their pregnancy until outcome.  
 
Treatment with bomedemstat and atezolizumab is not chemotherapy and is unlikely to 
cause temporary or permanent sterility. Please discuss with your study doctor any 
concerns about future fertility. 
 
What are the benefits? 
 
You may or may not receive any benefit from this investigational study. It is possible that 
you may get better, stay the same, or get worse.  
Your participation in this study may help future patients with this disease. 
 
Would you have extra costs if you join this study?  
 
If you join this study, you or your insurance company would have to pay for the costs of 
standard treatment and procedures related to your disease. 
 
You would not be billed for: 
 
• bomedemstat, the investigational drug. The drug manufacturer of this study, 
Imago BioSciences, Inc., will provide bomedemstat to you free of charge.  
 
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Will I be paid for my participation in this study? 
 
There is no payment for being in this study. 
 
What are my Other Treatment Options? 
 
• Instead of taking part in this investigational study, you may choose to receive 
standard treatment with other drugs and/or therapies that may be used to treat 
advanced cancers.  
• You could also participate in a research study or choose no treatment at all. The 
risks and benefits of these other treatments will be explained to you by your doctor. 
Your doctor will answer any questions you have about these other treatments. 
• If you decide that you don't want any more active treatment, one of your options is 
called "comfort care." Comfort care includes pain medication and other support.  It 
aims to maintain your comfort and dignity rather than cure disease. Usually this 
care can be provided at home. If you think you might prefer comfort care, please 
discuss this with your family, friends, and your doctor. 
Voluntary Participation and Withdrawal 
 
Taking part in this investigational study is voluntary. You do not have to participate in this 
investigational study. You can agree to be in this study now and change your mind later. 
Your decision will not affect your regular care or the benefits to which you are otherwise 
entitled. 
 
You can decide to stop at any time. Tell your doctor if you are thinking about stopping or 
decide to stop. Your doctor will tell you how to stop safely. 
 
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It is important to tell your doctor if you are thinking about discontinuing treatment on this 
investigational study. This is so you and your doctor can discuss what follow-up care, 
testing, and other treatments could be most helpful for you. 
 
If you participate in this study, we will collect your information. If you withdraw from the 
study, previously collected information would remain in our databases and may be 
included in the future analyses.  
 
Your doctor or the drug manufacturer may take you off this study at any time without your 
consent.  There are other reasons that you may be removed from the study including: 
 
• They think it is in your best interest not to continue to be treated on this study, 
• You are not able or willing to comply with the study, 
• The drug manufacturer stops providing the investigational drug, or 
• For any other reason. 
 
Rejoining the Study after Treatment for Central Nervous System Metastases 
 
If you participate in the study, your doctors will monitor your cancer using CT and/or MRI 
scans at regular intervals. If there is cancer growing in the brain and/or spinal cord (the 
central nervous system or CNS), one of two scenarios could occur: 
 
1. Your doctors determine that it is in your best interest not to receive further 
treatment in this study. They may recommend other forms of treatment such as 
radiation or other medications outside of this study. This is expected to be the most 
common scenario. 
 
2. Your doctors determine that it may be in your best interest to receive further 
treatment in this study after you receive treatment for the cancer in the CNS. 
Treatment for cancer in the CNS could consist of radiation or other treatments, and 
does not have to be administered by doctors that are affiliated with the study or 
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with the Fred Hutchinson Cancer Center. You could receive this treatment at a 
qualified medical facility that is convenient to you. Study treatment would be 
paused while you receive treatment for the cancer in the CNS. Once that treatment 
is completed, the study doctors will reassess whether resuming study treatment 
might be in your best interest. If they determine that resuming study treatment 
could be in your best interest, they will discuss with you the risks and benefits of 
resuming study treatment versus pursuing other treatment options (see Other 
Treatment Options section above). As at any other point in the study, you do not 
have to agree to continue participating in the study. This is expected to be the less 
common scenario.      
 
Confidentiality and Protecting Privacy of Personal Information 
 
The following information explains how your medical and health records may be used and 
disclosed. We will make every effort to keep your records private. 
 
If you consent to this study, information about your participation would be made part of 
your permanent medical record. This information would include a copy of this consent 
form. If an insurance company or employer or anyone else were authorized to see your 
medical record, they would see a copy of this consent form 
 
If you join this study, some people or organizations might need to look at your medical 
records and research records for quality assurance or data analysis.  
 
They include: 
 
• Imago BioSciences (the drug manufacturer) and their agents 
• Physicians and staff involved with this treatment. 
o Institutional Review Boards (IRB), including the Fred Hutchinson Cancer 
Center IRB. An IRB is a group that reviews the study to protect the rights 
and welfare of research participants. 
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• Fred Hutchinson Cancer Center, University of Washington. 
• Office for Human Research Protections, Food and Drug Administration, 
NIH/NCI and other regulatory agencies as required. 
 
The results of the study may be published in a medical book or journal or presented at 
meetings for educational purposes. If the results of this study are published, you will not 
be personally identified, and your identity will not be disclosed. During that time, results 
will be kept confidential to the extent permitted by law. Your participation in this study will 
be noted in your UW medical record. 
 
This research is covered by a Certificate of Confidentiality from the U.S. government. This 
Certificate helps protect the confidentiality of information about people who join this study. 
If you join the study, the Certificate means that generally we would not have to give out 
identifying information about you even if we were asked to by a court of law. We would 
use the Certificate to resist any demands for identifying information.  
 
We could not use the Certificate to withhold research information if you give written 
consent to give it to an insurer, employer, or other person.   
 
This protection has some limits. We would voluntarily provide the information:  
 
• To a member of the federal government who needs it in order to audit or 
evaluate the research.  
• To the funding agency and groups involved in the research, if they need the 
information to make sure the research is being done correctly.  
• To the federal Food and Drug Administration (FDA), if required by the FDA.  
• To someone who is accused of a crime, if he or she believes that our research 
records could be used for defense.  
• To authorities, if we learn of child abuse, elder abuse, or if participants might 
harm themselves or others.  
 
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What if you get sick or hurt after you join this study? 
 
For a life-threatening problem, call 911 right away or seek help immediately. Contact your 
study doctor when the medical emergency is over or as soon as you can. 
 
If you are injured or hurt as a result of taking part in this investigational study and need 
medical treatment, please tell your doctor and medical care will be provided to you. The 
costs of medical treatment will be billed to you or your insurance company.  Your 
insurance company may not be willing to pay for the investigational study related injury. 
If you have no insurance, you will be responsible for any costs. If you feel this injury was 
a result of medical error, you keep all your legal rights to receive payment for this even 
though you are participating in an investigational study. 
 
To help avoid injury, it is very important to follow all directions. 
  
We will bill you and your insurer for treatment of problems that result from your disease 
or standard clinical care. 
 
No money has been set aside to pay for things like lost wages, lost time, or pain. However, 
you do not waive any rights by signing this consent form. The above statements do not 
limit your legal rights. You still have the right to make a claim through the legal system 
even if you sign this consent form. By signing this consent form, you have not given up 
any of your legal rights to seek compensation. 
 
 
 
Will my information and/or tissue samples ever be use for future research? 
 
If you did have left over tissue, and provided to us, we might remove all identifiers and 
codes from the sample.  We could then use or share them with other researchers for 
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RG#1122005 
 
 
  
future research.  If you do not want your anonymous information or tissue samples used 
for other projects, you should indicate that on this consent. 
 
If you agree and we do share your information or tissue with others, we would not be able 
to stop the future research, even if you asked later.  There will be no way to link the 
information or tissue samples back to you. We will not contact you or otherwise inform 
you before we share your information or tissue for future research. 
 
Future genetic research databases 
Several genetic databases are available to help researchers understand different 
diseases. These databases contain DNA code and medical information from 
participants who have various diseases.  
As part of this study, we would like to release DNA code and information about your 
medical condition into a genetic database in order to help future research. The 
genetic database would not contain names, addresses, or other information that 
could be used to identify you.  
The DNA code in a genetic database cannot be used by itself to identify any specific 
person. A researcher who already has DNA code about you could use information 
from a genetic database to learn more about you. Once we release information to a 
genetic database, we no longer have any control over the use of this information.  
 
Your rights and Your responsibilities 
 
• You do not have to join this study. You are free to say “yes” or “no”.  
• If you get sick or hurt in this study., you do not lose any of your legal rights to seek 
payment by signing this form. 
 
• During the study, we might learn new information that you need to know. For example, 
some information may affect your health or well-being. Other information might make you 
change your mind about being in this study. If we learn these kinds of information, we 
would tell you. 
 
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RG#1122005 
 
 
  
• If you join this study, you would not have to stay in it. You could stop at any time (even 
before you start). Your regular medical care would not change. You would have no penalty 
for stopping, but it would be better not to join the study if you think that you would change 
your mind later.  
  
• If you decide to drop out, we would want you to tell the treating doctor. The doctor 
could tell you about the effects of stopping bomedemstat. You and the doctor could talk 
about the follow-up care and testing that would help the most.  
 
How is my genetic information protected? 
 
A federal law called the Genetic Information Nondiscrimination Act (GINA) helps protect 
genetic information about people who join research studies.  
 
GINA restricts access to genetic information so that it cannot be used for health 
insurance coverage decisions. GINA prevents health insurance companies or group 
health plans from:  
 
• 
Asking for genetic information obtained in research studies, or 
• 
Using genetic information when making decisions regarding your eligibility or 
premiums  
GINA does not help or protect against genetic discrimination by companies that sell life, 
disability or long-term care insurance. 
 
For more information 
If you have questions or concerns about this study, you could talk to your doctor 
anytime. Other people you could talk to are listed below. 
 
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RG#1122005 
 
 
  
If you 
have questions about: 
Call: 
This study (including 
complaints and requests for 
information) 
Dr. Rafael Santana-Davila (206) 606-2190 
If you get sick or hurt in this 
study 
Dr. Rafael Santana-Davila (206) 606-2190 
Rebecca Wood Research Mgr. (206) 606-6970 
Your rights as a research 
participant 
206-667-5900 or email irodirector@fredhutch.org 
(Director of Institutional Review Office, Fred 
Hutchinson Cancer Center) 
206-543-0098 (Human Subjects Division, 
University of Washington) 
Your bills and health 
insurance coverage 
The financial services department at Fred 
Hutchinson Cancer Center at (206) 606-6232 
 
Emergency number (24 hours): 206-598-6190 
 
Do you agree to donate your archival tissue if available to study cancer? 
 
(Circle One) 
 
YES   
NO  
 
 
Is it OK if we send your genetic information to one or more databases for future 
research? 
 
(Circle One) 
 
YES   
NO  
 
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RG#1122005 
 
 
  
 
Signature 
 
Please sign below if you:  
• have read this form (or had it read to you); 
 
• had the opportunity to ask any questions you have; 
• had the opportunity to discuss the research with the person obtaining consent.  
and  
 
• agree to participate in this study. 
 
 
 
 
Subject Name (printed) 
 
 
 
 
Signature of Subject                                                             Date 
 
 
 
I have discussed the research study, including procedures and risks, with the person 
signing above. A copy of the signed consent form will be given to the participant. 
 
 
 
 
Printed Name of Person Conducting Informed Consent Discussion 
 
 
 
 
 
Signature of Person Conducting Consent Discussion          Date 
 
 
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RG#1122005 
 
 
  
If you were a witness for a participant who was not able to read this written consent form, 
sign below to indicate (1) you were present at the consent discussion in person, (2) you 
witnessed the verbal presentation of the written consent form, and (3) the participant had 
the opportunity to ask questions and agreed to take part in the study. 
 
 
Impartial Witness: 
 
_________________________________________________ 
Printed Name 
 
 
 
 
_____________________________________________________________ 
Signature 
 
Date 
 
Current version date:  20220807 
Previous version date: 20220308 
Copies to: Participant and Medical Record 
FHCRC IRB Approval  
01/06/2023 
Document Released Date

Prot_SAP_002.pdf: 
 
 
Official Title: 
A PHASE I/II STUDY OF BOMEDEMSTAT COMBINED WITH 
MAINTENANCE IMMUNOTHERAPY FOR PATIENTS WITH 
NEWLY DIAGNOSED EXTENSIVE STAGE SMALL CELL LUNG 
CANCER (ES-SCLC) 
NCT Number: 
NCT05191797 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
1/6/2023 
 
 


Version 3.0 August 08, 2022 
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A PHASE I/II STUDY OF BOMEDEMSTAT COMBINED WITH MAINTENANCE 
IMMUNOTHERAPY FOR PATIENTS WITH NEWLY DIAGNOSED EXTENSIVE STAGE 
SMALL CELL LUNG CANCER (ES-SCLC)  
Protocol number: RG1122005 - IR10841 
IND #: 158720 
Principal Investigator:  
Rafael Santana-Davila, MD 
Professor 
University of Washington School of Medicine 
Ph: 206-606-6723 
Pager: 206-541-7960 
Fax: 206-606-2226  
Email: rsantana@seattlecca.org 
Sub Investigators: 
Christina Baik, MD 
Keith Eaton, MD, PhD 
Joseph Hiatt, MD, PhD 
Sylvia Lee, MD 
Cristina Merkhofer, MD 
Cristina Rodriguez, MD 
Diane Tseng, MD, PhD 
Nicolas Giustini, MD 
IRO REC'D 12/06/2022
FHCRC IRB Approval  
01/06/2023 
Document Released Date


 
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SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. Patients should receive study treatment until one of the treatment discontinuation reasons is met. 
Treatment discontinuation reasons are listed in Section 6.6. 
2. Disease assessments can be made within 7 days of the actual specified interval (e.g. 6 weeks +/- 
7 days). After 24 weeks of study treatment, disease assessments can be collected every 9 weeks 
+/- 7 days at the discretion of the investigator. 
 
 
STUDY ENROLLMENT  
Bomedemstat + atezolizumab 
maintenance therapy 
Disease Assessments every 6 weeks2 
Treatment 
discontinuation 
reasons not met1 
Progression 
Extensive stage SCLC receiving platinum 
+ etoposide + anti-PD(L)1 therapy 
Stable disease or better after 4 cycles  
Treatment Discontinuation  


 
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1.0 
OBJECTIVES......................................................................................................... 6 
1.1 
Primary Objectives ....................................................................................................................... 6 
1.2 
Secondary Objectives .................................................................................................................. 6 
1.3 
Additional Objectives ................................................................................................................... 6 
2.0 
BACKGROUND ..................................................................................................... 6 
2.1 
Newly Diagnosed Extensive Stage Small Cell Lung Cancer (ES-SCLC) ................................ 6 
2.2 
LSD1 Demethylase ....................................................................................................................... 6 
2.3 
Rationale for LSD1 Inhibition in SCLC ....................................................................................... 7 
2.4 
Existing Clinical Data on LSD1 Inhibition in SCLC ................................................................... 8 
2.5 
Possible Synergy Between LSD1 Inhibition and Immune Checkpoint Inhibition .................. 8 
2.6 
Bomedemstat ................................................................................................................................ 9 
2.7 
Bomedemstat Dose Justification ................................................................................................ 9 
3.0 
DRUG INFORMATION ........................................................................................ 10 
3.1 
Bomedemstat .............................................................................................................................. 10 
3.1.1 
Formulation ............................................................................................................................... 10 
3.1.2 
Storage ...................................................................................................................................... 11 
3.1.3 
Dispensing ................................................................................................................................ 11 
3.1.4 
Dosage ...................................................................................................................................... 11 
3.1.5 
Administration ........................................................................................................................... 11 
3.1.6 
Missed Doses ............................................................................................................................ 12 
3.1.7 
Dose Modifications for Toxicity ................................................................................................. 12 
3.2 
Atezolizumab ............................................................................................................................... 12 
3.2.1 
Formulation ............................................................................................................................... 12 
3.2.2 
Storage ...................................................................................................................................... 12 
3.2.3 
Dispensing ................................................................................................................................ 12 
3.2.4 
Dosage ...................................................................................................................................... 13 
3.2.5 
Administration ........................................................................................................................... 13 
3.2.6 
Missed Doses ............................................................................................................................ 13 
3.2.7 
Dose Modifications for Toxicity ................................................................................................. 13 
4.0 
STAGING CRITERIA ........................................................................................... 13 
5.0 
ELIGIBILITY CRITERIA ....................................................................................... 13 
5.1 
Inclusion Criteria ........................................................................................................................ 14 
5.2 
Exclusion Criteria ....................................................................................................................... 15 
6.0 
TREATMENT PLAN ............................................................................................ 17 
6.1 
Study Overview ........................................................................................................................... 17 
6.2 
Bomedemstat Dose Titration to Platelet Count ....................................................................... 18 
6.3 
Dose Modification for Toxicity .................................................................................................. 20 
6.4 
Prior and Concomitant Therapy ................................................................................................ 22 
6.4.1 
Required Prior or Concomitant Therapy ................................................................................... 22 


 
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6.4.2 
Allowed Concomitant Therapy .................................................................................................. 23 
6.4.3 
Prohibited Concomitant Therapy .............................................................................................. 23 
6.5 
Supportive Care Guidelines ...................................................................................................... 24 
6.6 
Discontinuation of Study Treatment and/or Withdrawal from Study for Individual Subjects
 
24 
6.6.1 
Disease progression ................................................................................................................. 24 
6.6.2 
Other criteria for discontinuation of study treatment and/or withdrawal .................................... 25 
7.0 
STUDY CALENDAR ............................................................................................ 26 
8.0 
STUDY PROCEDURES AND ASSESSMENTS .................................................. 28 
8.1 
Subject Enrollment ..................................................................................................................... 28 
8.1.1 
Informed Consent...................................................................................................................... 28 
8.1.2 
Inclusion/Exclusion Criteria ....................................................................................................... 28 
8.1.3 
Medical History.......................................................................................................................... 28 
8.1.4 
Prior and Concomitant Medications Review ............................................................................. 28 
8.1.5 
Disease Details ......................................................................................................................... 28 
8.1.6 
Prior Treatment Details ............................................................................................................. 28 
8.1.7 
Assignment of Patient Number ................................................................................................. 29 
8.2 
Clinical Procedures/Assessments ............................................................................................ 29 
8.2.1 
Adverse Event (AE) Monitoring ................................................................................................. 29 
8.2.2 
Concomitant Medications Review ............................................................................................. 29 
8.2.3 
Full Physical Exam .................................................................................................................... 29 
8.2.4 
Directed Physical Exam ............................................................................................................ 29 
8.2.5 
Vital Signs ................................................................................................................................. 29 
8.2.6 
ECOG Performance Status ....................................................................................................... 29 
8.2.7 
Radiographic Disease/Response Assessment ......................................................................... 29 
8.2.8 
Tumor Tissue Collection and Correlative Studies Blood Sampling .......................................... 30 
8.3 
Laboratory Procedures/Assessments ...................................................................................... 30 
8.3.1 
Laboratory Safety Evaluations (Hematology, Chemistry and Urinalysis) ................................. 31 
8.4 
Other Procedures ....................................................................................................................... 31 
8.4.1 
Treatment Discontinuation or Subject Withdrawal .................................................................... 31 
8.5 
Visit Requirements ..................................................................................................................... 32 
8.5.1 
Screening Period....................................................................................................................... 32 
8.5.2 
On Treatment Period ................................................................................................................ 32 
8.5.3 
Off Treatment Visits .................................................................................................................. 33 
8.6 
Assessing and Recording Adverse Events ............................................................................. 33 
8.6.1 
Serious Adverse Events ............................................................................................................ 34 
8.6.2 
Overdose ................................................................................................................................... 35 
8.6.3 
Pregnancy ................................................................................................................................. 35 
9.0 
CRITERIA FOR EVALUATION AND ENDPOINT ANALYSIS ............................ 36 
9.1 
Measurability of Lesions ............................................................................................................ 36 
9.1.1 
Measurable disease .................................................................................................................. 36 
9.1.2 
Non-measurable disease .......................................................................................................... 36 
9.1.3 
Notes on measurability ............................................................................................................. 36 
9.2 
Objective Status at Radiographic Evaluation .......................................................................... 37 
9.2.1 
Complete Response (CR) ......................................................................................................... 37 


 
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9.2.2 
Partial Response (PR) .............................................................................................................. 37 
9.2.3 
Stable Disease .......................................................................................................................... 37 
9.2.4 
Progressive Disease / Disease Progression (PD) .................................................................... 37 
9.2.5 
Relapse/Progression, Following Surgery .................................................................................. 38 
9.2.6 
Symptomatic Deterioration ........................................................................................................ 38 
9.2.7 
Assessment inadequate, objective status unknown ................................................................. 38 
9.2.8 
Objective status notes ............................................................................................................... 38 
9.3 
Best Response (RECIST 1.1 criteria) ........................................................................................ 39 
9.4 
Performance Status .................................................................................................................... 39 
9.5 
Dose-limiting Toxicity (DLT) Definition .................................................................................... 40 
9.6 
Progression-Free Survival (PFS) .............................................................................................. 40 
9.7 
Overall Survival (OS) .................................................................................................................. 40 
9.8 
Treatment Discontinuation Reasons (See Section 6.6) .......................................................... 41 
10.0 
STATISTICAL CONSIDERATIONS .................................................................. 41 
10.1 
Overview ...................................................................................................................................... 41 
10.2 
Safety Evaluation ........................................................................................................................ 41 
10.2.1 
Stopping Rule for Encephalopathy ........................................................................................... 41 
10.3 
Sample Size Justification and Analysis Plans ........................................................................ 41 
10.4 
Study Duration ............................................................................................................................ 42 
10.5 
Data and Safety Monitoring ....................................................................................................... 42 
11.0 
STUDY MANAGEMENT ................................................................................... 42 
11.1 
Monitoring of the study .............................................................................................................. 42 
11.2 
Data Management ....................................................................................................................... 42 
12.0 
ETHICAL CONSIDERATIONS ......................................................................... 43 
13.0 
ABBREVIATIONS ............................................................................................. 43 
14.0 
BIBLIOGRAPHY ............................................................................................... 43 
15.0 
APPENDIX ........................................................................................................ 46 
15.1 
VALG Staging Details ................................................................................................................. 46 
 
 


 
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1.0 
OBJECTIVES 
To evaluate the addition of bomedemstat to standard of care (SOC) maintenance atezolizumab following 
first line platinum-etoposide and immune checkpoint inhibitor therapy.  
1.1 
Primary Objectives 
1. Evaluate the percentage of patients alive and progression-free six months after initiating 
maintenance therapy with bomedemstat and atezolizumab. 
2. Evaluate the safety and tolerability of maintenance therapy with bomedemstat and atezolizumab. 
1.2 
Secondary Objectives 
1. Evaluate overall survival (OS).  
1.3 
Additional Objectives 
1. Evaluate the objective response rate in patients with measurable disease at the time of study 
enrollment.  
2. Collect blood and tumor tissue for correlative studies. 
2.0 
BACKGROUND 
2.1 
Newly Diagnosed Extensive Stage Small Cell Lung Cancer (ES-SCLC) 
Small cell lung cancer is an aggressive and highly lethal neuroendocrine neoplasm that represents 
approximately 15% of all lung cancer in the United States1. SCLC is usually metastatic at initial presentation 
and while induction chemotherapy leads to radiographic response in most patients, disease progression is 
often rapid and eventually occurs in virtually all patients. Following the onset of disease progression, 
treatment options are limited and outcomes are poor.  
Based on the remarkable activity in other tumor types and the high mutation burden in SCLC due to tobacco 
exposure, immune checkpoint inhibitors (ICIs) have been enthusiastically tested in clinical trials at various 
points in the natural history of SCLC2. However, in contrast to non-small cell lung cancer (NSCLC) and 
other tumor types with high mutation burden, results in SCLC have been modest at best. The Phase III 
trials IMpower1333 and CASPIAN4 reported a median overall survival (OS) benefit of approximately two 
months with the addition of ICI to first line chemotherapy.  Atezolizumab and durvalumab both received 
FDA approval for this indication, changing the SOC for newly diagnosed ES-SCLC patients. Despite this, 
the median overall survival of patients with ES-SCLC remains extremely poor at 12-13 months. This had 
led to several recent studies attempting to improve both the response to ICI as well as second line therapy 
options. The addition of an anti-CTLA4 antibody to an anti-PD1-containing regimen did not lead to improved 
outcomes in either first5 or later6 lines of therapy. Lurbinectedin received accelerated approval in 2020 
based on an uncontrolled Phase II study demonstrating a response rate of 35% in the second line, but 
persistently low OS at 9.3 months7. There remains an unmet need to identify novel therapeutics with activity 
in SCLC, as well as a need to elucidate rational biomarkers of patient subgroups with elevated probability 
of benefit8.  
2.2 
LSD1 Demethylase  
LSD1, also known as KDM1A, is an enzyme that plays a critical role in the regulation of gene expression 
via both its enzymatic activity and through interaction with partner proteins. Enzymatically, LSD1 removes 


 
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mono- and dimethyl groups from histone (H) H3 at critical lysines (K), K4 and K99. Methylation of histone 
H3K4 and H3K9 are post-translational modifications associated with changes in the confirmation of 
chromatin, the highly ordered complex of genomic DNA and associated proteins10,11. Changes in chromatin 
structure influence the accessibility of template DNA to the core transcriptional machinery, namely the RNA 
polymerase complex and key transcription factors (TFs), thereby influencing rates of gene transcription and 
subsequent protein synthesis10,11.  
LSD1 can also influence the local chromatin state through its interaction with partner proteins. Many TFs, 
both activators such as V-Myb Avian Myeloblastosis Viral Oncogene Homolog (MYB) and steroid hormone 
receptors, as well as repressors such as growth factor independence 1 transcription repressor (GFI1) and 
RE-1 silencing transcription factor (REST), recruit LSD1 to specific genomic locations12-14. LSD1 is part of 
a larger protein complex, also containing Co-RE-1 silencing transcription factor (CoREST) or nucleosome 
remodeling and histone deacetylase (NuRD), which dictates the cell- and site-specific chromatin 
remodeling15,16. These complexes may also include DNA methyltransferase 1 (DNMT1) and histone 
deacetylases 1, 2 or 3 (HDAC1, 2, or 3), all of which contribute to maintaining or modifying the epigenetic 
state at that genomic site17,18. Thus, an important property of LSD1 beyond its own enzymatic activity is its 
function as a scaffold for other proteins and epigenetic enzymes that are co-recruited to genomic sites. 
Likewise, LSD1 bound to specific sites precludes the binding of other factors that may influence 
transcription. LSD1 thereby regulates the epigenetic state of the cell by influencing the local state of 
chromatin at key lineage-defining genes via both enzymatic and non-enzymatic mechanisms. 
2.3 
Rationale for LSD1 Inhibition in SCLC 
SCLC does not harbor frequent mutations in “druggable” oncogenic drivers or tumor suppressors19-21. 
Instead, this neuroendocrine tumor type co-opts the same transcriptional programs necessary for normal 
lung neuroendocrine cell development to sustain tumor cell growth. Achaete-scute homolog 1 (ASCL1) is 
a transcription factor that promotes neuroendocrine transcriptional programs22,23, and the deletion of ASCL1 
strongly suppresses tumorigenesis in a genetically engineered mouse model of SCLC22. During lung 
development, NOTCH signaling negatively regulates ASCL123, and the activation of NOTCH family 
members also potently suppresses SCLC in mouse models19. Knowledge of these genetic dependencies 
has not had a clinical impact on the treatment of SCLC given the challenges of activating NOTCH or 
suppressing ASCL1 using conventional pharmacological approaches.  
SCLC also exhibits frequent mutations in chromatin-regulating genes19-21, leading to efforts to target the 
altered epigenetic landscapes of SCLC for therapeutic vulnerabilities. LSD1 is very highly expressed in 
SCLC tumors and cell lines. In a screen of >150 cancer cell lines across a variety of tumor types, the LSD1 
inhibitor GSK2879552 (GlaxoSmithKline) led to inhibition of proliferation in cell lines from two cancer types: 
acute myelogenous leukemia (AML) and SCLC24. In AML, LSD1 inhibition has been associated with pro-
differentiation phenotypes25 and LSD1 inhibitors are being tested in AML clinical trials26,27. LSD1 is also a 
potential therapeutic target for solid tumors, especially SCLC and other neuroendocrine tumors, and LSD1 
inhibitors have been moved into Phase 1 trials that include SCLC patients (e.g., Clinical Trial IDs 
NCT02712905, NCT02875223, and NCT02034123)28. 
Despite multiple studies identifying LSD1 inhibitors as potently growth suppressive to SCLC pre-clinical 
models, the mechanism of action had not been elucidated until recently, when variable sensitivity to LSD1 
inhibition in a panel of PDX models was exploited by scientists in the MacPherson lab at the Fred 
Hutchinson Cancer Center29. In brief, the LSD1 inhibitor ORY1001 showed heterogeneous tumor inhibitory 
effects in a panel of seven PDX models of SCLC, with one model (FHSC04, which was derived from a 
patient with chemo-resistant disease) exhibiting complete tumor regression with LSD1 inhibitor 
monotherapy. Molecular analyses of FHSC04 tumors that had been exposed to a short duration of LSD1 
inhibitor therapy showed strong upregulation of the NOTCH pathway, including NOTCH1, NOTCH2, and 
target genes HES1, HEY1 and REST29. While NOTCH acts as an oncogene in some cancer types, 
expression of active NOTCH1 suppressed SCLC in mouse models19 and NOTCH1 is the target of 
inactivating mutations in SCLC19, suggesting that NOTCH1 may be a SCLC tumor suppressor. NOTCH1 


 
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activation also results in suppression of the pivotal SCLC transcription factor ASCL130,31. ORY1001 
treatment induced a sharp reduction in ASCL1 protein levels in the FHSC04 model29. Activation of NOTCH 
causing suppression of ASCL1 could explain rapid tumor regression, as ASCL1 is critical for SCLC 
oncogenesis, with deletion of ASCL1 strongly suppressing SCLC in mouse models22. These mechanistic 
studies established robust activation of the NOTCH pathway and striking suppression of the transcription 
factor ASCL1 in response to pharmacologic inhibition of LSD129. Although these changes were greatest in 
the PDX model that was most sensitive to the LSD1 inhibitor, some level of activation of NOTCH signaling 
and ASCL1 suppression in response to LSD1 inhibition was commonly seen in the tested models29, 
suggesting that LSD1 inhibition alone could exert meaningful anti-tumor activity in a considerable fraction 
of patients with SCLC. 
2.4 
Existing Clinical Data on LSD1 Inhibition in SCLC 
A clinical trial describing monotherapy with the LSD1 inhibitor GSK2879552 in patients with relapsed or 
refractory SCLC was recently reported28. In this multicenter single-arm Phase I dose-escalation/-expansion 
trial, 29 patients were assigned to one of nine dose cohorts. As expected, thrombocytopenia was the most 
common dose-limiting toxicity, with Grade 3 or higher thrombocytopenia occurring in 10 patients (35%). 
Other recurrent Grade 3 or higher toxicities were anemia (1 patient), neutropenia (2 patients), asthenia (2 
patients), and encephalopathy (3 patients, one of which was grade 5). Eight patients underwent dose 
reduction due to thrombocytopenia and seven of those eight were receiving a dose of 2 mg daily or higher. 
Ten of the 29 patients on study received a dose of less than 2 mg daily. The disease control rate at week 
16 was 14% (4 of 29 patients). Of the 4 patients experiencing disease control at 16 weeks, three were 
receiving a dose of 2 mg daily or higher.  
Four patients on the study experienced encephalopathy: one at grade 2, two at grade 3, and one at grade 
5. Encephalopathy was not associated with distinctive imaging findings or a specific pathophysiology. In 
total, six drug-related serious adverse events were deemed to have occurred, of which four were 
encephalopathy. After three study holds due to encephalopathy adverse events, the decision was made to 
halt the study due to unfavorable risk-benefit profile.  
LSD1 is known to play a key role in neuronal differentiation and gene expression regulation32, and 
preclinical investigation revealed that GSK2879552 does cross the blood-brain barrier, suggesting a 
possible mechanistic explanation for the encephalopathy observed. Clinical studies of other LSD1 inhibitors 
that are not known to penetrate the central nervous system (CNS), such as ORY-100133 and bomedemstat, 
have not identified encephalopathy as a drug-related adverse event. It is therefore likely that a lack of CNS 
penetration is a necessary attribute of a clinically tractable LSD1 inhibitor. Furthermore, it is not possible to 
appreciate the anti-tumor efficacy of LSD1 inhibitor therapy in SCLC based on the described experience 
with GSK2879552 because a limited number of patients were treated at higher dose levels before the study 
was halted. 
2.5 
Possible Synergy Between LSD1 Inhibition and Immune Checkpoint Inhibition  
LSD1 expression is found in many tumor types and it has been proposed that LSD1 activity may be 
oncogenic through a variety of mechanisms, including direct repression of canonical tumor suppressor 
genes as well as establishment of a more “plastic” (permissive) epigenetic state that permits adaptive 
activation of various tumorigenic pathways including stemness and pro-proliferative gene expression 
programs34. More recently, it has become clear that LSD1 is involved in regulating the immune tumor 
microenvironment, and multiple lines of evidence now suggest that LSD1 inhibition could meaningfully 
potentiate the activity of immune checkpoint inhibitors in multiple tumor types, including (and, perhaps, 
especially) SCLC.  
Although not focused on SCLC, studies in multiple immunocompetent pre-clinical model systems have 
established a role for LSD1 in regulating tumor cell inflammatory gene expression and have suggested that 


 
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LSD1 inhibition can potentiate immune checkpoint inhibitor therapy35,36. Tumors in mice treated with anti-
PD-1 antibody alone grew unabated whereas the addition of pharmacologic36 or genetic35 inhibition of LSD1 
was associated with dramatic suppression of tumor growth. Mechanistic studies revealed several lines of 
evidence in support of this phenotype. LSD1 inhibition led to de-repression of silenced retroviral elements 
in the cellular genome and suppression of several RNA-induced silencing complex (RISC) components35. 
The net result of these changes was markedly increased accumulation of double-stranded RNA (dsRNA) 
in the cytoplasm, which was sensed by intracellular pattern recognition receptors and activated a pro-
immunogenic interferon signaling cascade35. LSD1 inhibition therefore led to increased expression of pro-
immunogenic and T cell-attracting chemokines such as CXCL9 and CXCL1035. Methylation patterns at the 
promoters of these key immunogenic genes were also altered, suggesting that LSD1 might also directly 
target these genes to maintain an immunosuppressive state in the unperturbed cancer cell35. These studies 
were carried out in tumor models that were poorly immunogenic at baseline, highlighting the potential for 
LSD1 inhibition to improve the efficacy of immunotherapy in contexts where it has not historically provided 
substantial benefit. Gene expression profiling in patient tumors also revealed a negative correlation 
between LSD1 expression and levels of pro-inflammatory gene transcripts, further supporting an 
immunosuppressive role for LSD135,36. LSD1 inhibition is therefore an appealing strategy to boost anti-
tumor immunity and response to immune checkpoint inhibition in patients, but this has not yet been tested 
in clinical trials.  
More recently, additional evidence has emerged to support the potentially immunogenic role of LSD1 
inhibition in SCLC. It was first observed almost forty years ago that SCLC cell lines exhibited defects in 
antigen presentation37, and this phenomenon has been proposed as a potential explanation for the modest 
and heterogeneous efficacy of immunotherapy in patients with SCLC. Still, it was not clear whether antigen 
presentation machinery (APM) defects were correlated with other genetic or epigenetic features of SCLC. 
Multiple recent studies of SCLC patients and model systems have linked reduced expression of canonical 
neuroendocrine (NE) genes (such as ASCL1) and increased expression of the NOTCH pathway to 
increased intra-tumoral inflammatory gene expression signatures and, critically, improved outcomes after 
exposure to immune checkpoint inhibitors38-42. Indeed, increased NOTCH pathway activity is associated 
with recovery of APM expression and function, and overexpression of a NOTCH pathway member induced 
recovery of APM expression in a SCLC model42. As discussed above, the MacPherson lab has shown that 
LSD1 inhibition consistently leads to downregulation of NE genes and upregulation of NOTCH signaling in 
a spectrum of SCLC models. LSD1 is therefore a promising candidate therapeutic target to potentiate the 
activity of immunotherapy in SCLC. Indeed, in unpublished data, the MacPherson lab has shown that LSD1 
inhibition synergizes with immune checkpoint blockade in an immunocompetent murine model. 
2.6 
Bomedemstat  
Bomedemstat (formerly IMG-7289) is an orally available, irreversible inhibitor of LSD1 which demonstrates 
activity against LSD1 in human AML cells at concentrations of less than 5 nM. Irreversible inhibitors of 
LSD1 include tranylcypromine (TCP) which has been used for the treatment of depression for decades. 
The targets of TCP therapy, however, include all FAD-dependent monoamine oxidases (MAOs) in addition 
to LSD1. TCP inactivates LSD1 in a manner identical to its action on MAO-A and MAO-B because these 
three enzymes share a similar oxidative chemistry. Bomedemstat, however, inhibits MAO-A with an IC50 of 
~27 uM and MAO-B with an IC50 of ~34 uM, thereby exhibiting a high degree (>4000-fold) of selectivity for 
LSD1. Pharmacokinetic studies in mouse, rat and dog and pharmacokinetic modeling in human systems 
suggest that once-daily dosing in humans would achieve therapeutic exposures without significant drug 
accumulation. In the treatment of more than 160 patients in completed or ongoing Phase 2 studies, a single 
case of encephalopathy has occurred; no other major safety signals have been observed43,44. 
2.7 
Bomedemstat Dose Justification 
LSD1 plays a key role in hematopoietic stem/progenitor cell proliferation and differentiation45 and lineage-
specific myelosuppression is therefore an expected mechanism-based outcome of LSD1 inhibition28. LSD1 


 
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inhibition has its greatest effects on thrombopoiesis, granulopoiesis, and lastly erythropoiesis with 
monopoiesis being unaffected28. These effects are dose-dependent and fully reversible upon withdrawal of 
treatment.  
Chronic toxicity studies in rat (26-week) and dog (39-week) were conducted in which bomedemstat was 
administered once-daily at doses up to 6 and 1.5 mg/k/d, respectively. These studies concluded the toxicity 
observed was due to exaggerated pharmacological effect on specific lineages of myeloid hematopoiesis. 
Animals showed a dose-dependent decrease in platelets and, to a lesser extent in red cell number and 
neutrophil counts, with an increase in monocytes and no effect on the number of circulating lymphocytes. 
There was no evidence that inhibition of LSD1 affected the function of any terminally differentiated 
circulating cells. In the 26-week rat toxicity study, the no-observed-adverse-effect level (NOAEL) was 2 
mg/kg/d; in the 39-week dog toxicology study, the NOAEL was 1 mg/kg/d. 
In the CTP-101 study, bomedemstat was administered to patients with high-risk AML and MDS; the 
therapeutic thesis was to completely inhibit LSD1 in all hematopoietic cells, targeting both leukemic stem 
cells and blasts, recognizing that patients would need clinical support for cytopenias. The starting dose was 
0.75 mg/kg/d and the optimal dose, at which no safety signals have been observed, was deemed to be 6.0 
mg/kg/d. Patients at all dose levels of bomedemstat required platelet transfusions, although the sensitivity 
of thrombopoiesis to LSD1 inhibition in high-risk AML/MDS patients likely reflects the generally 
compromised nature of the bone marrow, including the reduction of megakaryocytes, in that disease. 
Subsequently, bomedemstat is being tested in ongoing Phase 2 studies for the treatment of myelofibrosis43 
and essential thrombocythemia44. In these studies, bomedemstat dosing is titrated to a target platelet count, 
and a starting dose of 0.6 mg/kg/d was eventually selected for both studies as optimal to efficiently achieve 
a therapeutic exposure in individual patients (the RP2D)43. In the myelofibrosis study, which has fully 
enrolled with 89 patients, there have been fourteen serious adverse events (SAEs) attributed to 
bomedemstat, all of which were grade 3 or lower with the exception of one Grade 4 thrombocytopenia in 
which a dosing error may have contributed43. In the essential thrombocythemia study, albeit with lower 
patient accrual (n=30), four SAEs have been observed, both deemed unrelated to bomedemstat by 
Investigators44. No dose-limiting toxicities, safety signals, or deaths due to study drug were observed in 
either study.  
We therefore hypothesize that a starting dose of 0.5 mg/kg/d for all patients with a platelet count 
≥100x103/mcL, and 0.4 mg/kg/d for patients with a platelet count of 75-99x103/mcL, of bomedemstat free 
base (to account for recent receipt of myelosuppressive chemotherapy) will be well-tolerated and will 
achieve therapeutically relevant levels in patients with extensive stage SCLC completing induction 
chemoimmunotherapy and transitioning to maintenance treatment.  
3.0 
DRUG INFORMATION 
3.1 
Bomedemstat 
Bomedemstat is an investigational drug that will be supplied by the Imago Biosciences. Details regarding 
bomedemstat formulation, storage, dispensing, dosage, administration, etc., are described in an 
accompanying pharmacy manual. 
3.1.1 
Formulation 
The drug product is bomedemstat, a bis-tosylate salt. The free base of bomedemstat is the active moiety. 
Bomedemstat will be supplied in capsules of multiple strengths. These strengths, based on bomedemstat 
free base, i.e. the active substance, may include: 5 mg, 10 mg, 25 mg, and 50 mg. Additional strengths 
may be added over the duration of the study. Such details will be included via updates to the Pharmacy 
Manual. Details on capsules, including strengths, colors, and sizes, can be found in the pharmacy manual. 


 
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3.1.2 
Storage 
The recommended long-term storage conditions for bomedemstat are for the storage temperature not to 
exceed 25°C. Bomedemstat must be stored in a secure area with access limited to the Investigator and 
authorized staff and under the physical conditions that are consistent with bomedemstat-specific 
requirements. Bomedemstat supplies will be stored securely under the appropriate conditions according to 
the federal, state and local laws. Procedures for bomedemstat storage and accountability are detailed in a 
pharmacy manual. 
3.1.3 
Dispensing 
All material supplied is for use only in this clinical study and should not be used for any other purpose. Only 
patients enrolled in the study may receive study drug, in accordance with all applicable regulatory 
requirements. Only authorized site staff may dispense study drug. 
The Investigator is responsible for bomedemstat accountability, reconciliation and record maintenance per 
Site Standard Operating Procedure.  
3.1.4 
Dosage 
All patients will be treated daily until disease progression that meets criteria to discontinue treatment, or 
unacceptable toxicity (see Section 6.6). Dosing will begin on Day 1 at the starting dose (Ds), which is 0.5 
mg/kg/d bomedemstat free base for all patients with a platelet count ≥100x103/mcL, and 0.4 mg/kg/d for 
patients with a platelet count of 75-99x103/mcL. The calculated dose will be rounded to the nearest 5 mg 
increment for dispensation and administration. Details on the selection of and rationale for the starting dose 
and dosing schedule can be found in Section 2.7. 
Using dose titration, all patients will be dosed to the bomedemstat Dpi (platelet inhibitory dose), which 
reflects the on-target activity of the drug. The Dpi, is anticipated to be ≤2 mg/kg/d; however, this is not the 
upper limit for titration purposes as the dose needed to achieve a therapeutic effect will vary among patients 
and may change over time. The platelet titration target expected to be associated with a clinically significant 
therapeutic effect is a platelet count of approximately ≥50x103/mcL to ≤99x103/mcL. Titration and re-
challenge rules based on evaluation of platelet, ANC, and Hgb counts are described in Section 6.2. The 
maximum dose is 6 mg/kg/d. 
Bomedemstat dosing will be based on the patient's weight on the first day of study treatment. If during the 
study the patient's weight differs from Day 1 by more than 10%, the amount of bomedemstat dispensed 
should be updated to the current weight. The source data must clearly document the weight used. 
In the event of uncertainty regarding dose modification of bomedemstat for adverse events, or uncertainty 
regarding management of clinically significant changes in platelets, neutrophil counts, or other hematologic 
parameters, the PI should be consulted.  
3.1.5 
Administration 
Appropriately trained personnel of the study site will provide instruction pertaining to bomedemstat 
administration. All bomedemstat doses will be self-administered by the patient off-site. 
Patients should be instructed to: 
1. Take their bomedemstat once daily, at night before bed at approximately the same time (suggest 
that patient select their dosing time with consideration given to fasting requirements). 
2. Swallow their bomedemstat capsules whole, with a glass of water. 


 
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3. Take bomedemstat on an empty stomach (fast for 1 hour prior to and 30 minutes after dose). 
Patients may have clear liquids prior to their dose and following study drug administration. 
Patients may take other medications at the same time as bomedemstat. 
3.1.6 
Missed Doses 
Patients who do not take their bomedemstat dose at the usual required time should take it immediately 
upon noting that it was not taken; however, the patient should not take the dose more than 12 hours after 
the usual dosing time. If a patient misses a dose, they should not take two doses the following day, but 
should notify their study coordinator and continue with their normal daily dose the following day.  
For a dosing hiatus due to a serious adverse event (SAE), please consult the Principal Investigator for 
guidance on dosing re-start. Patients who miss an extended number of bomedemstat doses or exhibit serial 
non-compliance with treatment may be removed from the study at the discretion of the Principal 
Investigator.  
3.1.7 
Dose Modifications for Toxicity 
See Section 6.2 and 6.3 as appropriate to the specific toxicity. 
3.2 
Atezolizumab 
Please see the current Package Insert provided by the manufacturer for detailed information regarding 
atezolizumab46. Atezolizumab (Tencentriq, Genentech) is a commercially available programmed death-
ligand 1 (PD-L1) blocking antibody indicated for the treatment of multiple solid tumors including SCLC and 
its safety and efficacy are well-characterized.  
3.2.1 
Formulation  
Atezolizumab injection for intravenous use is a sterile, preservative-free, colorless to slightly yellow solution 
in single-dose vials. Each 20 mL vial contains 1200 mg of atezolizumab and is formulated in glacial acetic 
acid (16.5 mg), L-histidine (62 mg), polysorbate 20 (8 mg), and sucrose (821.6 mg), with a pH of 5.8.  
3.2.2 
Storage 
Atezolizumab injection is a sterile, preservative-free, and colorless to slightly yellow solution for intravenous 
infusion supplied as a carton containing one 1,200 mg/20 mL single-dose vial (NDC 50242-917-01). 
Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not 
freeze. Do not shake. 
3.2.3 
Dispensing 
3.2.3.1 Preparation 
Visually inspect drug product for particulate matter and discoloration prior to administration, whenever 
solution and container permit. Discard the vial if the solution is cloudy, discolored, or visible particles are 
observed. Do not shake the vial. Prepare the solution for infusion as follows. Withdraw the required volume 
of atezolizumab from the vial(s) using sterile needle and syringe. Dilute to a final concentration between 
3.2 mg/mL and 16.8 mg/mL in a polyvinyl chloride (PVC), polyethylene (PE), or polyolefin (PO) infusion bag 
containing 0.9% Sodium Chloride Injection, USP. Dilute with only 0.9% Sodium Chloride Injection, USP. 
Mix diluted solution by gentle inversion. Do not shake. Discard used or empty vials of atezolizumab.  


 
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3.2.3.2 Storage of Infusion Solution 
This product does not contain a preservative. Administer immediately once prepared. If diluted 
atezolizumab infusion solution is not used immediately, store solution either: 
1. At room temperature for no more than 6 hours from the time of preparation. This includes room 
temperature storage of the infusion in the infusion bag and time for administration of the infusion, 
or 
2. Under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours from time of 
preparation. 
Do not freeze. Do not shake. 
3.2.4 
Dosage 
Administer atezolizumab as 1200 mg every 3 weeks. 
3.2.5 
Administration 
Please see the manufacturer’s package insert for administration instructions. 
3.2.6 
Missed Doses 
Patients who do not receive an intended atezolizumab infusion should have the infusion administered as 
soon as possible. If an intended infusion is delayed by more than 48 hours, the Principal Investigator should 
be consulted to guide dosing re-start. Patients who miss an extended number of bomedemstat doses or 
exhibit serial non-compliance with treatment may be removed from the study at the discretion of the 
Principal Investigator. 
3.2.7 
Dose Modifications for Toxicity 
Please see the manufacturer’s package insert for detailed information regarding dosage modification for 
toxicities of atezolizumab.  
4.0 
STAGING CRITERIA 
Limited stage (LS) and extensive stage (ES) disease are defined as follows: 
1. Limited stage disease: Tumor and any metastases to regional lymph nodes (hilar, mediastinal, or 
ipsilateral supraclavicular) are confined to one hemithorax and can be encompassed in a single 
radiation port. 
2. Extensive stage disease: Extension of disease beyond the areas defined for limited disease.  
Note: A cytologically confirmed malignant pleural effusion constitutes extensive stage disease. 
Patients who have progressed following treatment for limited stage small cell lung cancer are 
considered to have extensive stage disease. 
See Section 15.1 for VALG staging details. 
5.0 
ELIGIBILITY CRITERIA 
Subjects must meet all the enrollment criteria to be eligible for this study. Eligibility criteria may not be 
waived by the investigator. 


 
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5.1 
Inclusion Criteria  
Patients must meet all of the following applicable criteria to be eligible for enrollment: 
1. Adult aged 18 years or older and willing and able to provide written informed consent.  
2. Histologically confirmed diagnosis of extensive stage small-cell lung cancer (ES-SCLC).  
Note: Previously treated limited stage SCLC (LS-SCLC) patients are eligible if disease 
progression had occurred following completion of definitive treatment for LS-SCLC. Determination 
of disease progression after prior therapy for LS-SCLC is at the discretion of the investigator. 
3. Having received four cycles of platinum-etoposide concurrent with three or four cycles of immune 
checkpoint inhibitor as induction systemic therapy for ES-SCLC immediately prior to study 
enrollment (see below for definitions). Note that immune checkpoint inhibitor may have been 
omitted from the first cycle only. 
Platinum is defined as cisplatin or carboplatin. Immune checkpoint inhibitor is defined as 
atezolizumab, durvalumab, or other anti-PDL1 or anti-PD1 monoclonal antibody that is approved 
by the US Food and Drug Administration for first-line treatment of ES-SCLC in combination with 
platinum and etoposide at the time of treatment receipt. Immediately prior is defined as receipt of 
Cycle 1 Day 1 of platinum-etoposide +/- immune checkpoint inhibitor no more than 112 days prior 
to Cycle 1 Day 1 of study treatment, and administration of fourth cycle of platinum-etoposide and 
immune checkpoint inhibitor no more than 30 days prior to Cycle 1 Day 1 of study treatment. 
4. Eligible to receive maintenance atezolizumab, as defined by stable disease or better, following 
induction platinum-etoposide and immune checkpoint inhibitor. Determination of response to 
induction therapy is at the discretion of the investigator. Investigators should contact the PI if 
clarification is needed. 
5. ECOG performance status of ≤ 2. 
6. Minimum life expectancy of ≥ 12 weeks. 
7. Satisfactory laboratory parameters: 
a. Absolute neutrophil count (ANC) ≥ 1000/mcL  
Note: myeloid growth factor use within 14 days of study treatment initiation is not permitted. 
Growth factor may have been previously administered during induction 
chemoimmunotherapy.  
b. Platelet count (Plt) ≥ 75x103/mcL (without transfusion) 
c. Hemoglobin (Hgb) ≥ 8.0 g/dL (transfusion is permitted) 
d. Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) ≥ 40 mL/min 
or serum creatinine ≤ 1.5x upper limit of normal 
e. Serum total bilirubin ≤ 1.5x upper limit of normal (ULN) or ≤ 3x ULN for subjects with Gilbert’s 
disease 
f. 
Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x ULN (≤ 
5x ULN if evidence of hepatic involvement by malignant disease) 


 
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g. The following coagulation parameters must be met only in patients not receiving 
anticoagulant agents at baseline.  
i. international normalized ratio (INR) < 1.5x upper limit of normal 
ii. activated partial thromboplastin time (aPTT) < 1.5x the local upper limit of normal 
Note: there is no INR or aPTT threshold for patients who are receiving anticoagulant 
agents at baseline, but patients must be on a stable dose of anticoagulant, and 
discontinuation of all anticoagulation while the platelet count is below 50x103/mcL 
must be deemed appropriate for the patient by the investigator prior to enrollment 
(see Section 5.2).   
8. Able to swallow capsules. 
9. Amenable to peripheral blood sampling during the study. 
10. Female subjects of childbearing potential should be willing to use 2 methods of birth control or 
abstain from heterosexual activity for the course of the study through 28 days after the last dose 
of study medication. Subjects of childbearing potential are those who have not been surgically 
sterilized or have not been free from menses for >1 year.  
11. Male subjects who are sexually active with female partner(s) of childbearing potential should be 
willing to use an adequate method of contraception starting with the first dose of study therapy 
through 28 days after the last dose of study therapy. 
5.2 
Exclusion Criteria  
Subjects meeting any of the following exclusion criteria are not eligible for study participation: 
1. Prior receipt of systemic therapy for ES-SCLC other than four cycles of induction platinum-
etoposide and immune checkpoint inhibitor (see Section 5.1 for definitions of these terms). 
2. Diagnosis of LS-SCLC that has not been previously treated. 
3. Receipt of radiation therapy for symptomatic deterioration and/or radiographic disease 
progression that was administered after initiation of induction platinum-etoposide and immune 
checkpoint inhibitor.  
Note: the presence of untreated asymptomatic brain metastasis, or a history of receipt of radiation 
to brain metastasis that was not initiated in response to symptomatic deterioration and/or 
radiographic disease progression following initiation of induction systemic therapy, does not 
preclude study participation. Investigators should contact the PI if clarification is needed. 
4. Anticipated use of prophylactic cranial irradiation or consolidative thoracic radiation therapy 
during study participation.  
Note: Palliative radiation to the CNS for new CNS disease that develops during study 
participation is allowed (Section 8.2.7.1). 
5. History of prior immune-related adverse event or other toxicity associated with immune 
checkpoint inhibitor that precludes safe administration of maintenance atezolizumab, in the 
opinion of the investigator. 


 
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6. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of 
study treatment. The following are exceptions to this criterion: 
a. Intranasal, inhaled, topical steroids or local steroid injections (e.g., intra-articular injection). 
b. Systemic corticosteroids at doses not to exceed 10 mg/d of prednisone or equivalent. 
c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). 
7. Active autoimmune disease requiring systemic immunosuppression or history of autoimmune 
disease requiring systemic immunosuppression within the last 2 years.  
Note: Systemic immunosuppression should be interpreted as systemic glucocorticoids at a dose 
of greater than 10 mg/day of prednisone or equivalent, systemic biologic agents including 
monoclonal antibodies against inflammatory mediators, or small molecule agents. Investigators 
should contact the PI if clarification is needed. 
8. Active pneumonitis or interstitial lung disease (ILD), or a history of pneumonitis/ILD, which 
required systemic immunosuppression (e.g. corticosteroids). 
9. Known bleeding disorder (e.g., dysfibrinogenaemia, factor IX deficiency, hemophilia, Von 
Willebrand's disease, Disseminated Intravascular Coagulation [DIC], fibrinogen deficiency, or 
other clotting factor deficiency), at the discretion of the investigator. 
10. History of severe thrombocytopenia or platelet dysfunction, including: immune thrombocytopenic 
purpura; thrombotic microangiopathy including thrombotic thrombocytopenic purpura, hemolytic-
uremic syndrome, complement-mediated thrombotic microangiopathy, or drug-induced thrombotic 
microangiopathy; inherited platelet function disorders, including Bernard-Soulier Syndrome, gray 
platelet syndrome, Wiskott-Aldrich Syndrome, Glanzmann Thrombasthenia, or Chediak-Higashi 
Syndrome. Investigators should contact the PI if a patient has a history of severe 
thrombocytopenia due to a cause not listed here or if any other clarification is needed. 
11. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related 
to bomedemstat or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that 
contraindicates their participation. 
12. Any hypersensitivity to PD-1/PD-L1 targeting agents. 
13. Current use of monoamine oxidase A and B inhibitors (MAOIs). 
14. Current use of a prohibited medication (e.g. romiplostim) or expected to require any of these 
medications during treatment with the investigational drug. 
15. Current or anticipated use of an antiplatelet (e.g. clopidogrel), anticoagulant (e.g. warfarin or 
apixaban), or NSAID with antiplatelet activity (e.g. aspirin, ibuprofen), that, in the opinion of the 
investigator, could NOT be safely discontinued when the subject’s platelet count decreases below 
50x103/mcL.  
16. Has undergone major surgery within 4 weeks prior to starting study drug and/or has not 
recovered from side effects of such surgery. Note: Major surgery and recovery are defined at the 
discretion of the investigator. 
17. Receipt of a live vaccine within 30 days of first dose of study therapy. 
18. Uncontrolled active infection. 


 
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19. Any concomitant active malignancy considered clinically significant by the investigator. 
20. Known human immunodeficiency virus (HIV) infection or known active Hepatitis B or Hepatitis C 
virus infection (testing will not be conducted as part of Screening procedures). 
21. History of any illness/impairment of gastrointestinal (GI) function that might interfere with drug 
absorption (e.g. chronic diarrhea), confound the study results or pose an additional risk to the 
patient by participation in the study. 
22. Use of an investigational agent within 28 days, or the equivalent of at least 7 half-lives of that 
agent, whichever is the shorter, prior to the study Day 1. 
23. Females who are pregnant or breastfeeding or plan to become pregnant or breastfeed at any 
time during the study. 
6.0 
TREATMENT PLAN 
6.1 
Study Overview 
This is an open label, single arm, single institution Phase 1-2 study testing the activity and tolerability of the 
LSD1 inhibitor bomedemstat in combination with maintenance immune checkpoint inhibitor (ICI) in patients 
with newly diagnosed extensive stage SCLC treated with first-line induction platinum-etoposide and ICI. 
Bomedemstat dosing will be titrated to platelet count suppression (an on-target toxicity). Consideration of 
bomedemstat dose escalation will occur on an every three week schedule. As such, for convenience, all 
patients will receive the ICI atezolizumab in combination with bomedemstat, including patients who received 
a different ICI as part of induction with platinum-etoposide.  
The starting dose of bomedemstat will be determined according to the screening platelet count as follows. 
For patients with a platelet count of ≥100x103/mcL, the starting dose will be 0.5 mg/kg/d. For patients with 
a platelet count of 75-99x103/mcL, the starting dose will be 0.4 mg/kg/d. See Sections 2.7 and 3.1.4 for 
bomedemstat starting dose selection rationale. A safety evaluation will be performed as described in 
Section 10.2 and the starting dose will be modified accordingly, if necessary.  
Bomedemstat will be administered orally, once daily, for a 21-day cycle. Bomedemstat should be taken on 
an empty stomach. See Section 3.1.5 for detailed administration instructions. Because bomedemstat 
exhibits on-target toxicity of lineage-specific myelosuppression that preferentially affects platelet 
production, bomedemstat dosing will be titrated to a target platelet count of 50-99x103/mcL as described in 
Section 6.2. Detailed guidance regarding bomedemstat dose modification for toxicities (including 
myelosuppression) is described in Section 6.3.  
Atezolizumab will be administered via IV infusion at a flat dose of 1,200 mg every 3 weeks in keeping with 
the medication’s prescribing information regarding standard of care use46.  
Subjects who at any time experience severe toxicity meeting criteria for treatment discontinuation (see 
Section 6.6.2) will not be eligible for further study treatment and will be converted to Off Treatment status.  
Radiographic disease response assessments will occur every 6 weeks +/- 7 days (after completion of 24 
weeks of study treatment, the interval can be extended to every 9 weeks +/- 7 days at the discretion of the 
investigator) for the duration of study participation with disposition based on the results as follows:  
1. Subjects who experience disease response (CR or PR) or stable disease without evidence of 
clinical deterioration will continue bomedemstat and atezolizumab maintenance therapy. Absence 
of clinical deterioration is determined by the treating physician and is defined as follows: 


 
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a. Absence of signs and symptoms of disease progression. 
b. Absence of rapid disease progression. 
c. Absence of progressive tumor at critical anatomical sites (e.g. cord compression) requiring 
urgent alternative medical intervention. 
2. Subjects who experience disease progression that is isolated to the CNS are eligible to continue 
study treatment following definitive therapy to the CNS disease, provided that ongoing study 
treatment is likely to provide additional benefit to the patient, at the discretion of the investigator 
and after appropriate discussion with the patient. See Section 8.2.7.1 for further details. 
3. Subjects who experience confirmed disease progression by RECIST 1.1 (other than isolated CNS 
progression) and/or clinical deterioration should discontinue study treatment (see Section 6.6.1).  
Note: Subjects with unconfirmed disease progression by RECIST 1.1 who do not have evidence 
of clinical deterioration may continue to receive study treatment, at the discretion of the 
investigator and after appropriate discussion with the patient. Subjects should be monitored 
closely and a follow-up scan should be performed after 28 days, or sooner if clinical deterioration 
occurs. If the follow-up scan confirms disease progression, the subject should discontinue study 
treatment. See Section 8.2.7.2 for further details.  
Subjects will be followed closely until disease progression per RECIST 1.1 or initiation of new anticancer 
treatment, whichever occurs first; and will afterwards be followed for survival until death or study 
termination, whichever occurs first. Blood samples for biomarker assessments will be collected at protocol-
defined timepoints to support study endpoints. 
6.2 
Bomedemstat Dose Titration to Platelet Count 
Bomedemstat dose titration to platelet count will be performed according to the titration and re-challenge 
rules described in Table 6.1 and Table 6.2 as follows. Dose titration rules use the absolute platelet count 
and the relative change from the most recent scheduled assessment. Prior to cycle 2 day 1, dose increases 
are not permitted, and dose titration should be performed according to Table 6.1. Starting on Day 1 of cycle 
2, dose increases are permitted, and dose titration should be performed according to Table 6.2. The 
maximum allowed dose is 6 mg/kg/d. Dose increases require adequate neutrophil and erythrocyte indices, 
and dose increases are not permitted within 21 days of a previous dose change, where change is inclusive 
of dose increase or dose reduction. After a dose hold, when platelets have returned to >50x103/mcL, the 
subject should be re-challenged with bomedemstat at 50% of the previous dose. Dose reductions for safety 
reasons are permitted at any time. 
 
Table 6.1. Bomedemstat titration to goal platelet count and re-challenge rules for cycle 1, days 8 and 15. 
Platelet Assessment 
Rules 
Platelet count (x 
103/mcL) 
Change in Platelet 
Count Relative to 
Previous Scheduled 
Assessment  
Titrate Dose? 
Titration Rule 
Re-challenge Rule 
≥100 
Any, including same 
count 
Maintain 
N/A 
N/A 
50-99 
Any increase or same 
count 
Maintain 
N/A 
N/A 


 
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50-99 
<50% decrease1 
Down-titrate1 
Decrease current 
dose by 0.1 mg/kg1 
N/A 
50-99 
≥50% decrease1 
Down-titrate1 
Decrease current 
dose by 0.2 mg/kg 
if starting dose was 
0.5 mg/kg or by 0.1 
mg/kg if starting 
dose was 0.4 
mg/kg1 
N/A 
<50 
Any change1 
HOLD DOSE1 
HOLD DOSE1 
Resume at 50% of 
previous dose when 
platelets return to 
>50x103/mcL.2 
1. 
If pseudothrombocytopenia due to blood sample coagulation or platelet clumping is suspected, the CBC should be 
repeated. If the second blood draw confirms that the first draw yielded a falsely low platelet count, the result of the 
first draw should be ignored and the dose of bomedemstat calculated based on the result of the second draw.  
2. 
ANC ≥ 1.0 x 103/mcL (1.0 x 109/L) and Hgb ≥ 8 g/dL (80 g/L) are needed for or re-challenge. 
 
 
 


 
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Table 6.2. Bomedemstat titration to goal platelet count and re-challenge rules for all days with CBC evaluation 
in cycle 2 and beyond. 
Platelet Assessment 
Rules 
Platelet count (x 
103/mcL) 
Change in Platelet 
Count Relative to 
Previous Scheduled 
Assessment 
Titrate Dose? 
Titration Rule 
Re-challenge Rule 
≥200 
Any, including same 
count 
Up-titrate1,2,3 
Increase current 
dose by 0.15 
mg/kg 
N/A 
100-199 
<75% decrease4 or 
same count or any 
increase 
Up-titrate1,2,3 
Increase current 
dose by 0.1 mg/kg 
N/A 
100-199 
≥75% decrease4 
Maintain4 
N/A 
N/A 
50-99 
<50% decrease4 or 
same count or any 
increase 
Maintain4 
N/A 
N/A 
50-99 
≥50% decrease4 
Down-titrate4 
Decrease current 
dose by 0.1 mg/kg 
or 25%, whichever 
results in a lower 
dose 
N/A 
<50 
Any change4 
HOLD DOSE4 
HOLD DOSE5 
Resume at 50% of 
previous dose when 
platelets return to > 
50x103/mcL.1 
1. 
ANC ≥ 1.0 x 103/mcL (1.0 x 109/L) and Hgb ≥ 8 g/dL (80 g/L) are needed for up-titration or re-challenge. 
2. 
Dose up-titration is not permitted if any dose change (including up- or down-titration) has occurred within the 
previous 21 days. 
3. 
The maximum allowed dose of bomedemstat is 6 mg/kg/d. 
4. 
If pseudothrombocytopenia due to blood sample coagulation or platelet clumping is suspected, the CBC should be 
repeated. If the second blood draw confirms that the first draw yielded a falsely low platelet count, the result of the 
first draw should be ignored and the dose of bomedemstat calculated based on the result of the second draw. 
5. 
Prophylactic platelet transfusion is at the discretion of the treating investigator. Prophylactic platelet transfusion is 
strongly encouraged for platelet count < 10x103/mcL. 
6.3 
Dose Modification for Toxicity 
Toxicity will be graded using Common Terminology Criteria for Adverse Events (CTCAE version 5.03). 
Dose modification of bomedemstat for hematologic toxicities is listed in Table 6.3. Please note that use of 
hematopoietic growth factors is prohibited during study participation (see Section 6.4.3). Dose modification 
of bomedemstat for other toxicities potentially related to bomedemstat is listed in Table 6.4. If multiple 
toxicities suggesting conflicting dose modifications are present simultaneously, the rule that results in the 
lowest bomedemstat dose should be followed. 
Dose modification, interruption, or discontinuation of atezolizumab for toxicity should be performed 
according to the prescribing information46. 


 
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Subjects that require more than three down-titrations or dose holds of bomedemstat will render the subject 
ineligible for further treatment in the study and the subject will be converted to Off Treatment status.  
Furthermore, encephalopathy of any grade is always considered a serious adverse event as well as an 
unacceptable toxicity and should result in immediate treatment discontinuation (see Sections 8.6.1 and 
10.2.1). 
Table 6.3. Dose modification of bomedemstat related to hematologic toxicities. 
Toxicity 
Grade 
Management1 
Neutropenia 
3 
(ANC 0.5-1x103/mcL) 
Continue bomedemstat dosing and maintain dose 
level. 
4 
(ANC <0.5x103/mcL) 
Hold bomedemstat dosing until ANC recovery to 
≥1.0x103/mcL. Reduce dose by 0.1 mg/kg/d upon 
reinitiating. 
Febrile Neutropenia 
≥3 
Hold bomedemstat dosing for at least 7 days and until 
ANC recovery to ≥1.0x103/mcL. Reduce dose by 0.1 
mg/kg/d upon reinitiating. 
Anemia 
3 
(Hgb <8 g/dL) 
Continue bomedemstat dosing and maintain dose 
level. Transfusion of red blood cells is at the discretion 
of the treating physician and does not require 
bomedemstat dose modification. 
4 
(Life-threatening 
consequences; urgent 
intervention indicated) 
Hold bomedemstat dosing until Hgb recovery to ≥8 
g/dL. Reduce dose by 0.1 mg/kg/d upon reinitiating. 
Thrombocytopenia 
See Table 6.1 and  
Table 6.2. 
Lymphopenia 
Any 
Dose interruption or study discontinuation is not 
required for lymphopenia of any grade. 
1. 
Use of hematopoietic growth factors is prohibited during study participation (see Section 6.4.3). 
 
 
Table 6.4. Dose modification of bomedemstat related to non-hematologic toxicities. 
Type 
Grade 
Management 
Hold 
treatment? 
Timing for 
restarting 
treatment 
Dose/schedule for 
restarting/treatment 
Discontinue 
subject? (After 
consultation with 
PI) 
Non-laboratory 
1 
No 
N/A 
N/A 
N/A 
2 
Consider 
withholding for 
persistent 
symptoms 
Toxicity 
resolves to 
Grade 0-1 or 
baseline 
Reduce dose by 0.1 
mg/kg/d upon 
reinitiating. 
Toxicity does not 
resolve to Grade 
≤1 or baseline 


 
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3, lasting >3 
days despite 
optimal 
supportive 
care 
Yes 
within 4 weeks of 
last dose. 
Permanent 
discontinuation 
should be 
considered for any 
severe or life-
threatening event. 
4 
Yes 
Laboratory, non-
hematologic or 
hematologic not 
listed in Table 7-
4 
1-2 
Consider 
withholding for 
clinically 
significant 
abnormalities 
following 
consultation 
with study PI 
N/A 
N/A 
N/A 
3-4, if medical 
intervention is 
required or 
abnormality 
leads to 
hospitalization 
Yes 
Toxicity 
resolves to 
Grade 0-1 or 
baseline 
Reduce dose by 0.1 
mg/kg/d upon 
reinitiating. 
Toxicity does not 
resolve to Grade 
≤1 within 4 weeks 
of last dose. 
Permanent 
discontinuation 
should be 
considered for any 
severe or life-
threatening event. 
 
In case clinically significant non-hematologic toxicity does not resolve to Grade 0-1 or baseline within 4 
weeks after last dose of any study treatment, investigational treatment with bomedemstat should be 
permanently discontinued, and the subject should be converted to Off Treatment status. Clinical 
significance is at the discretion of the investigator. With investigator and sponsor agreement, subjects with 
a non-hematologic laboratory adverse event still at Grade 2 after 4 weeks may continue treatment in the 
study and retain On Treatment status only if asymptomatic and controlled.  
Subjects who experience a recurrence of the same severe or life-threatening event at the same grade or 
greater following re-challenge of bomedemstat are not eligible for further study treatment and should be 
converted to Off Treatment status. 
6.4 
Prior and Concomitant Therapy 
Prior therapies include systemic therapies, radiation, and surgeries.   
Any concomitant therapy given for a study protocol related AE should be recorded from Cycle 1 Day 1 of 
study treatment through the Safety Follow-Up Visit. 
6.4.1 
Required Prior or Concomitant Therapy 
Subjects must have received four cycles of platinum-etoposide and three or four cycles of ICI immediately 
prior to study enrollment (for details, see Section 5.0). 


 
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6.4.2 
Allowed Concomitant Therapy 
Standard supportive care measures for symptom control or drug related toxicity are allowed, such as 
analgesics, antiemetics, electrolyte replacement, and hydration. Other prescribed medications for non-
neoplastic conditions are allowed, as well as vitamins and nutritional or herbal supplements, which must be 
recorded in the medication list. 
Concomitant corticosteroids (prednisone or equivalent) may be used at a dose of ≤10 mg/day. The use of 
intermittent high dose corticosteroid treatment to prevent or manage hypersensitivity reactions or other 
noncancer-related symptoms is allowed (including premedication for known hypersensitivity reactions to 
contrast material for imaging scans). 
Routine prophylaxis with vaccines is permitted, excluding those containing live microorganisms. 
If the subject is taking chronic suppressive anti-infectives (e.g., antiviral, antifungal, or antibacterial), 
appropriate evaluation must be completed prior to registration, and documentation must exclude active 
infection. The subject should continue suppressive anti-infectives for the duration of study participation. 
Birth control or contraceptive measures are allowed. 
6.4.3 
Prohibited Concomitant Therapy 
Subjects are prohibited from receiving the following therapies during trial participation: 
1. Any other systemic anti-cancer therapy, including chemotherapy, immunotherapy, or biologic 
therapy not specified in this protocol. 
2. Any investigational agents not specified in this protocol. 
3. Monoamine oxidase A and B inhibitors (MAOIs). 
4. All hematopoietic growth factors: romiplostim, eltrombopag, granulocyte and granulocyte-
macrophage colony stimulating factor (G-CSF and GM-CSF) and erythropoietin (EPO). 
5. Systemic corticosteroids at a dose of >10 mg/d (prednisone equivalent).  
Note: The use of intermittent high dose corticosteroid treatment to prevent or manage 
hypersensitivity reactions or other symptoms not related to cancer is allowed (including 
premedication for known hypersensitivity reactions to contrast material for imaging scans). 
6. Radiation therapy, including prophylactic cranial irradiation and consolidative thoracic radiation 
therapy. Note that radiation therapy for isolated CNS progression is allowed, during which time 
bomedemstat should be held (see Section 8.2.7.1). 
7. Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the 
trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, 
rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza 
vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal 
influenza vaccines (e.g. Flu-Mist®) are live-attenuated vaccines and are not allowed.  
8. Subjects are specifically prohibited from receiving the following therapies while the platelet count 
is < 50x103/mcL:  
a. Non-steroidal anti-inflammatory medications with COX-1 inhibitory/antiplatelet activity (e.g. 
aspirin, ibuprofen, naproxen, etc.). 


 
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b. Antiplatelet agents, e.g. clopidogrel, prasugrel, ticagrelor, ticlopidine. 
c. Anticoagulation with warfarin, Factor Xa inhibitors (e.g. apixaban, edoxaban, rivaroxaban), 
direct thrombin inhibitors (e.g. dabigatran), or low molecular weight heparins (enoxaparin, 
dalteparin). 
6.5 
Supportive Care Guidelines 
Subjects should receive appropriate supportive care measures as deemed necessary by the treating 
investigator including but not limited to the items outlined below: 
1. Anti-infectives: Subjects with a documented infectious complication should receive oral or IV 
antibiotics or other anti-infective agents as considered appropriate by the treating investigator for 
a given infectious condition, according to standard institutional practice. 
2. Immune-related adverse events: Immune-related adverse events should be managed in keeping 
with institutional and national guidelines47.  
3. Infusion reactions while receiving atezolizumab: Acute infusion reactions should be managed 
according to institutional guidelines. 
4. Transfusions: transfusions of red blood cells and platelets are at the discretion of the investigator 
and should be performed in accordance with institutional guidelines. Prophylactic transfusion of 
platelets when the platelet count is < 10x103/mcL is strongly encouraged. 
6.6 
Discontinuation of Study Treatment and/or Withdrawal from Study for Individual Subjects  
Specific criteria for discontinuation of study treatment and/or withdrawal from study are listed in Sections 
6.6.1 (disease progression) and 6.6.2 (other reasons).  
Subjects may withdraw consent at any time for any reason or be withdrawn from the trial at the discretion 
of the investigator should any untoward effect occur. In addition, a subject may be withdrawn by the 
investigator or the Sponsor if enrollment into the trial is inappropriate, the trial plan is violated, or for 
administrative and/or other safety reasons. 
Subjects who meet criteria to discontinue study treatment will be converted to Off Treatment status and will 
be followed per the Study Calendar (Section 7.0) via the End of Treatment Visit and Survival Follow-up 
assessments (see Section 8.5.3), including the collection of any protocol-specified blood specimens, unless 
consent is withdrawn, or the subject is lost to follow-up or enrolled in another clinical study.  
Subjects who discontinue study treatment for a reason other than disease progression and have not 
initiated other anti-cancer therapy will be followed with Monitoring assessments (Section 8.5.3.3).  
All subjects will be followed for survival. Subjects who decline to return to the site for evaluations will be 
offered follow-up by phone every 3 months as an alternative. 
6.6.1 
Disease progression 
Confirmed radiographic disease progression per RECIST 1.1 (Section 9.2.4) renders a subject ineligible for 
further study treatment, except that isolated CNS progression does not require permanent study treatment 
discontinuation (see Section 8.2.7.1 for further detail).  
In the event of unconfirmed disease progression, study treatment can be continued until disease 
progression is confirmed (see Section 8.2.7.2 for further detail). 


 
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6.6.2 
Other criteria for discontinuation of study treatment and/or withdrawal 
An individual subject will not receive any further study treatment and will proceed to Off Treatment 
monitoring if any of the following occur in the subject in question: 
1. The subject withdraws consent. 
2. Unacceptable adverse events as defined in Section 6.3.  
Note that encephalopathy of any grade is always considered an unacceptable adverse event (see 
Section 10.2.1). 
3. Adverse event that, in the opinion of the investigator, contraindicates further dosing. 
4. Subject noncompliance that, in the opinion of the investigator, warrants withdrawal, e.g., refusal 
to adhere to scheduled visits. 
5. Subject is determined to have met one or more of the exclusion criteria for study participation at 
study entry and continuing investigational therapy might constitute a safety risk. 
6. Intercurrent illness that prevents further administration of treatment. 
7. Investigator’s decision to withdraw the subject. 
8. The subject has a confirmed positive serum pregnancy test. 
9. Noncompliance with trial treatment or procedure requirements. 
10. The subject is lost to follow-up. 
11. Grade ≥ 3 infusion reaction.  


 
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7.0 
STUDY CALENDAR 
Title/Cycle 
Screening 
On Treatment  21 Day Cycles 
Off Treatment 
 
 
 
Every 
Treatment 
Cycle 
 
 
 
End of 
Treatment 
Monitoring 
Safety Follow-
Up 
Survival 
Follow-Up 
Timing 
Day -28 to 1 
Day 1 
Day 8 
Day 15 
Within 7 days 
of Day 1 of 
next cycle 
Time of 
discontin. 
~Q8w 
30d after 
discontinuation 
of study 
treatment 
~Q12w 
Window (days) 
- 
+/- 2 (subseq. 
cycles) 
+/- 2 
+/- 2 
+ 7 
+/- 7 
+/- 14 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Inclusion / Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
Demographics / Medical History / 
Prior and Concomitant 
Medication Review 
X 
 
 
 
 
 
 
 
 
Bomedemstat Administration1 
 
Daily 
 
 
 
 
 
 
 
Atezolizumab Administration2 
 
X 
 
 
 
 
 
 
 
Survival Status 
 
 
 
 
 
 
 
 
X 
Adverse Event / Concomitant 
Medication Review3 
 
X3 
 
 
 
X 
X 
X 
 
Full Physical Examination 
X 
 
 
 
 
 
 
 
 
Directed Physical Examination3 
 
X3 
 
 
 
X 
X 
X 
 
Vital Signs and Weight 
X 
X 
 
 
 
X 
X 
X 
 
ECOG Performance Status 
X 
X 
 
 
 
X 
X 
X 
 
Pregnancy Test 
X 
 
 
 
 
 
 
 
 
Complete Blood Count with 
Differential (CBC w/ Diff)4 
X 
X 
X4 
X4 
 
X 
X 
X 
 
Comprehensive Serum 
Chemistry Panel 
X 
X 
 
 
 
X 
X 
X 
 
PT/INR and aPTT 
X 
 
 
 
 
 
 
 
 
Serum cortisol, FT4, TSH 
 
X 
 
 
 
 
 
 
 
Archival tissue collection 
X 
 
 
 
 
 
 
 
 
Blood for correlative research 
X 
X 
 
 
 
X 
X 
 
 
Disease/response assessment5 
X5 
 
 
 
X5 
 
X5 
 
 
1. Bomedemstat is taken daily. All doses are self-administered by the patient off-site. 
2. Atezolizumab is administered in the clinic as an IV infusion. There are no specific restrictions regarding timing relative to the patient’s bomedemstat dose.  
3. Note that, during On Treatment status, provider visits (to facilitate AE/concomitant medication review and physical examination) are only required on Day 1 of each treatment cycle. 
Visits on other cycle days, including Day 8 and Day 15, can be performed if clinically necessary but are not mandated.  
4. Weekly CBC w/ diff required throughout Cycle 1. After Cycle 1, CBC w/ diff should be performed weekly until the patient has not required a bomedemstat dose modification or hold for 
at least 28 days, at which point CBC w/ diff can be spaced out to no less frequently than every 14+/-2 days. If a dose modification is subsequently required, weekly CBC w/ diff should 
resume until at least 28 days have elapsed without need for a dose modification or hold, at which point CBC w/ diff can again be spaced out to no less frequently than every 14+/-2 days. 


 
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5. Disease/response assessment during the screening period may have been performed up to 14 days prior to initiation of study treatment. Disease response assessments will occur 
every 6 weeks. After completion of 24 weeks of study treatment, the intervals can be extended to up to 9 weeks +/- 7 days. CT scans should encompass at least the chest and abdomen. 
CT pelvis should be included according to usual clinical practice. For patients who are known to have CNS disease at the time of study enrollment, monitoring of the CNS should proceed 
according to usual clinical practice. 


 
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8.0 
STUDY PROCEDURES AND ASSESSMENTS 
The Study Calendar (Section 7.0) summarizes the study procedures to be performed at each visit. Individual 
study procedures are described in detail below. It may be necessary to perform these procedures at 
unscheduled time points if deemed clinically necessary by the investigator. 
8.1 
Subject Enrollment 
8.1.1 
Informed Consent 
The Investigator must obtain documented consent from each potential subject prior to participating in the 
study. 
Consent must be documented by the subject’s dated signature on a consent form along with the dated 
signature of the person conducting the consent discussion. 
A copy of the signed and dated consent form should be given to the subject before participation in the trial 
per Institutional Standards. 
The initial informed consent form, any subsequent revised written informed consent form and any written 
information provided to the subject must receive the IRB/ERC’s approval/favorable opinion in advance of 
use. The subject should be informed in a timely manner if new information becomes available that may be 
relevant to the subject’s willingness to continue participation in the trial. The communication of this 
information will be provided and documented via a revised consent form or addendum to the original 
consent form that captures the subject’s dated signature. 
The informed consent will adhere to IRB/ERC requirements, applicable laws and regulations and Sponsor 
requirements. 
8.1.2 
Inclusion/Exclusion Criteria 
All inclusion and exclusion criteria will be reviewed by the investigator or qualified designee to ensure that 
the subject qualifies for the trial. 
8.1.3 
Medical History 
A medical history will be obtained by the investigator or qualified designee. Medical history will include all 
active conditions, and any condition diagnosed within the prior 10 years that is considered clinically 
significant by the Investigator. Details regarding the disease for which the subject has enrolled in this study 
will be recorded separately and not listed as medical history. 
8.1.4 
Prior and Concomitant Medications Review 
The investigator or qualified designee will review prior medication use, including any protocol-specified 
washout requirement. 
8.1.5 
Disease Details 
The investigator or qualified designee will obtain prior and current details regarding disease status. 
8.1.6 
Prior Treatment Details 
The investigator or qualified designee will review all prior cancer treatments including systemic treatments, 
radiation, and surgeries. 


 
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8.1.7 
Assignment of Patient Number 
Patients will be assigned a Patient Number upon consent. 
8.2 
Clinical Procedures/Assessments 
The following clinical assessments should be performed in accordance with the Study Calendar (Section 
7.0). 
8.2.1 
Adverse Event (AE) Monitoring 
The investigator or qualified designee will assess each subject to evaluate for potential new or worsening 
AEs. Adverse experiences will be graded and recorded throughout the study according to NCI CTCAE 
Version 5.03. Toxicities will be characterized in terms regarding seriousness, causality, toxicity grading, 
and action taken regarding investigational treatment. 
Please refer to Section 8.6 for detailed information regarding the assessment and recording of AEs. AE 
monitoring may occur more frequently than required as clinically indicated. 
8.2.2 
Concomitant Medications Review 
The investigator or qualified designee will review prior medication use, including any protocol-specified 
washout requirement. 
8.2.3 
Full Physical Exam 
The investigator or qualified designee will perform a complete physical exam. Clinically significant abnormal 
findings should be recorded as medical history.  
8.2.4 
Directed Physical Exam 
For timepoints that do not require a full physical exam, the investigator or qualified designee will perform a 
directed physical exam as clinically indicated prior to study treatment administration. 
8.2.5 
Vital Signs 
The investigator or qualified designee will measure and record vital signs, including temperature, pulse, 
respiratory rate, weight, and blood pressure. 
8.2.6 
ECOG Performance Status 
The investigator or qualified designee will assess ECOG Performance Status (see Section 9.4). 
8.2.7 
Radiographic Disease/Response Assessment 
Radiographic assessments of measurable disease will be performed using CT imaging with IV contrast. CT 
scans should encompass at least the chest and abdomen. CT pelvis should be included according to usual 
clinical practice. RECIST 1.1 criteria will be used to assess response to therapy. Radiographic imaging will 
be performed every 6 weeks (42 +/- 7 days). After completion of 24 weeks of study treatment, the interval 
between radiographic evaluations can be extended to up to 9 weeks +/- 7 days, according to the discretion 
of the investigator. For patients who are known to have CNS disease at the time of enrollment, CNS imaging 
should be performed during study participation according to usual clinical practice. 


 
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8.2.7.1 Isolated Central Nervous System Progression 
Isolated CNS progression does not require discontinuation of study treatment. Bomedemstat should be 
held for seven days prior to until seven days following the administration of CNS-directed therapy (e.g. a 
standard course of whole brain radiotherapy or stereotactic radiosurgery, in accordance with institutional 
practice). The subject may then resume study therapy when clinically appropriate. If more than 4 weeks 
have elapsed since the previous dose of study drug, the subject should undergo a radiographic disease 
assessment before restarting study treatment. 
8.2.7.2 Treatment Beyond Initial Determination of Progression 
If a subject has unconfirmed PD (Section 9.2.4) and is clinically stable and without symptomatic 
deterioration (Section 9.2.6), it is at the discretion of the Investigator to continue study treatment per protocol 
until PD is confirmed (Section 9.2.4). For subjects with new lesions, the diameters of the new lesions will 
be recorded. 
Clinically stable is defined as: 
1. Absence of symptoms and signs indicating clinically significant PD (including worsening of 
laboratory values). 
2. Absence of rapid progression of disease or progressive tumor at critical anatomical sites (eg, cord 
compression) requiring urgent alternative medical intervention. 
Upon confirmation of PD (Section 9.2.4) or onset of symptomatic deterioration / loss of clinical stability, 
study treatment should be discontinued. Administration of study treatment beyond confirmed progression 
is not permitted. 
8.2.8 
Tumor Tissue Collection and Correlative Studies Blood Sampling 
Archival tumor tissue (defined as 10-15 serial sections, each 4 microns thick, mounted onto positively 
charged glass slides, or a block) will be requested as part of study participation. However, adequate archival 
tissue is not a requirement for study participation. Archival tissue samples will be tested for 
immunohistochemical expression studies of key markers which may include PD-L1, ASCL1, ATOH1, 
NEUROD1, POU2F3, REST, and YAP1. 
Peripheral blood samples for correlative research studies should be collected in two to three 10 mL lavender 
top (EDTA) or Streck cfDNA tubes (~20-30 mL per collection). Research blood collections will be performed 
for correlative research studies at the following timepoints: during screening, at every radiographic 
assessment, and at end of treatment visit, regardless of whether radiographic assessment was performed. 
If radiographic assessment intervals are extended due to durable clinical benefit, research blood collection 
intervals will be extended to match.  
Correlative studies will be performed in the MacPherson lab at the Fred Hutchinson Cancer Center in 
Seattle, WA. Correlative studies will include isolation of circulating tumor cells for multi-omic analysis (e.g. 
measurements of DNA alterations, mRNA transcript levels, and protein abundance) and the generation of 
patient-derived xenograft models, to isolate circulating free DNA (cfDNA) for multidimensional analysis (e.g. 
DNA alterations, fragmentation patterns), and to isolate genomic DNA from peripheral blood mononuclear 
cells for more accurate identification of somatic mutations. The goal of correlative studies is to identify 
predictors of clinical benefit from bomedemstat in combination with atezolizumab. 
8.3 
Laboratory Procedures/Assessments 
Details regarding specific laboratory procedures/assessments to be performed in this study are provided 
below. 


 
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8.3.1 
Laboratory Safety Evaluations (Hematology, Chemistry and Urinalysis) 
Laboratory tests for hematology, chemistry, urinalysis, and others are specified in Table 8.1. Results must 
be reviewed by the investigator or qualified designee and found to be acceptable prior to initiation of the 
next cycle of study treatment.  
Table 8.1. Laboratory tests. 
CBC w/ Diff 
Complete serum chemistry panel 
Other 
Hematocrit 
Alanine aminotransferase (ALT) 
Activated partial thromboplastin 
time (aPTT) 
Hemoglobin 
Albumin 
Cortisol, serum 
Platelet count 
Alkaline phosphatase 
Prothrombin time (PT/INR) 
White blood cell count (total) 
Aspartate aminotransferase (AST) 
Serum beta-human chorionic 
gonadotropin (β-hCG) (required if 
urine test is inconclusive) 
Red blood cell count 
Bilirubin, Total 
Thyroid stimulating hormone (TSH) 
Absolute neutrophil count 
Blood Urea Nitrogen 
Thyroxine, free (FT4) 
 
Carbon dioxide (CO2 or Bicarbonate) 
Urine pregnancy test (only for 
women of childbearing potential) 
 
Chloride 
Blood for correlative studies 
 
Creatinine 
 
 
Glucose 
 
 
Potassium 
 
 
Protein, Total 
 
 
Sodium 
 
 
8.4 
Other Procedures 
8.4.1 
Treatment Discontinuation or Subject Withdrawal 
When a subject discontinues study treatment permanently or withdraws prior to trial completion, all 
applicable activities should be performed at the time of discontinuation (Section 7.0). Any adverse events 
which are present at the time of discontinuation/withdrawal should be followed in accordance with the safety 
requirements outlined in Section 8.6. An End of Treatment visit (Section 8.5.3.1) should be performed within 
7 days. If the subject has not experienced disease progression (see Section 8.2.7) and has not withdrawn 
from the study, the subject should undergo regular Monitoring visits (Section 8.5.3.3) for disease 
assessment according to the Study Calendar (Section 7.0). 


 
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8.5 
Visit Requirements 
Visit requirements are outlined in the Study Calendar (Section 7.0). Specific procedure-related details are 
provided above in Clinical Procedures/Assessments (Section 8.2). 
8.5.1 
Screening Period 
The following assessments will be performed up to 14 days prior to Cycle 1 Day 1: 
1. Full Physical Examination 
2. Vital Signs and weight 
3. ECOG Performance Status 
4. Pregnancy test or Serum β-HCG in females of childbearing potential 
5. CBC w/ Diff 
6. PT/INR and aPTT 
7. Comprehensive serum chemistry panel  
8. Archival tissue collection, if available 
9. Radiographic disease assessment (see Section 8.2.7). 
a. CT with IV contrast of the chest and abdomen. CT pelvis should be included according to 
usual clinical practice. For patients known to have CNS disease, CNS imaging should be 
performed according to usual clinical practice. 
10. Blood for correlative studies 
8.5.2 
On Treatment Period 
The following assessments will be performed at On Treatment Period visits as identified in the Study 
Calendar 
(Section 
7.0). 
Specific 
procedure-related 
details 
are 
provided 
above 
in 
Clinical 
Procedures/Assessments (Section 8.2). 
1. Adverse event review 
2. Concomitant medication review 
3. Directed physical examination 
4. Vital signs and weight 
5. ECOG performance status 
6. CBC with differential 
7. Comprehensive serum chemistry panel 
8. TSH, FT4, and random serum cortisol  
9. Radiographic disease/response assessment (see Section 8.2.7) 


 
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10. Blood for correlative studies (see Section 8.2.8) 
8.5.3 
Off Treatment Visits 
8.5.3.1 End of Treatment Visit 
The mandatory End of Treatment visit should be conducted at the time of permanent study treatment 
discontinuation, or within 7 days thereafter, unless the patient is unable to participate in the visit. 
8.5.3.2 Safety Follow-Up Visit 
The mandatory Safety Follow-Up Visit should be conducted approximately 30 days after cessation of study 
treatment, or before the initiation of a new anti-cancer treatment outside the confines of this study, 
whichever comes first, unless the patient is unable to participate in the visit. All AEs that occur prior to the 
Safety Follow-Up Visit should be recorded. 
8.5.3.3 Monitoring  
Subjects who discontinue study treatment for a reason other than disease progression or withdrawal from 
study move into the monitoring phase and should be assessed radiographically every 8 weeks (56 ± 7 days) 
as in Section 8.2.7 to monitor disease status. Every effort will be made to collect information regarding 
disease status until the start of new anti-neoplastic therapy, disease progression, death, or end of the study. 
Information regarding post-study anti-neoplastic treatment will be collected if new treatment is initiated. 
8.5.3.4 Survival Follow-up  
Once a subject is no longer eligible for study treatment due to disease progression or starts a new anti-
cancer therapy outside the confines of this study, the subject moves into the survival follow-up phase. 
Survival status of the subject will be ascertained every 12 weeks, via medical records or by directly 
contacting the patient, until death, withdrawal of consent, or the end of the study, whichever occurs first. 
Three attempts to contact a subject should be made before the subject is considered lost to follow up. 
8.6 
Assessing and Recording Adverse Events 
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have to have a causal relationship 
with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a 
medicinal product or protocol-specified procedure, regardless of whether the event is considered related to 
the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse 
change in frequency and/or intensity) of a preexisting condition that is temporally associated with receipt of 
study therapy, is also an adverse event. 
Adverse events may occur during study therapy or within the follow-up period specified by the protocol, 
from overdose (whether accidental or intentional), from abuse and from withdrawal. 
Only adverse events that meet the following definition will be recorded: 
1. All grade 3 and higher adverse events 
2. Grade 1-2 adverse events that require medical intervention, i.e. initiation of a new medication, or 
are otherwise clinically significant at the discretion of the investigator   
3. Any adverse event that requires a dose reduction or dose delay of either bomedemstat or 
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Adverse events will be recorded from Cycle 1 Day 1 until the Safety Monitoring visit performed according 
to the Study Calendar (Section 7.0), using the Adverse Event case report forms/worksheets. For subjects 
who discontinue study therapy for a reason other than disease progression and are being followed with 
Monitoring visits (Section 8.5.3.3), adverse events should continue to be monitored. Adverse events related 
to either bomedemstat or atezolizumab will be followed until resolution or stabilization of the AE or until the 
beginning of a new anti-neoplastic therapy, whichever occurs first. The reporting timeframe for adverse 
events meeting any serious criteria is described below. 
8.6.1 
Serious Adverse Events 
SAEs will be reported promptly, using the SAE Report Form, once the Investigator determines that the 
event meets the protocol definition of an SAE.  The Investigator or designee will report the SAE within 24 
hours of his/her becoming aware of these events regardless of relationship of the SAE to the use of study 
drug, in accordance with the instructions in the SAE Report Form Completion Guidelines. The Investigator 
will always provide an assessment of relatedness at the time of the initial report.  The SAE Report will 
always be completed as thoroughly as possible with all available details of the event within the designated 
time frames. Copies of relevant patient records, autopsy reports, and other documents may be requested.    
A detailed SAE reporting procedure and contact information will be included in the SAE Report Form 
Completion Guidelines which will be finalized before any patients are consented.  If the Investigator does 
not have all information regarding an SAE, he/she will not wait to receive additional information before 
reporting the SAE. The SAE Report will be updated when additional information is received within 24 hours 
of receipt of such information.  
The Institutional Review Board (IRB) must be notified in writing of any SAEs that require expedited reporting 
to Regulatory Authorities.  All SAEs meeting expedited reporting requirements will be reported to FDA in 
accordance with reporting requirements.   
A Serious Adverse Event (SAE), which must be reported to the Principal Investigator within 24 hours of 
awareness via pager, is any adverse event that meets any of the following criteria:  
1. Fatal (i.e., the adverse event directly causes or leads to death) 
2. Life-threatening (i.e., the adverse event, in the view of the Investigator, places the subject at 
immediate risk of death). Note: this does not include any adverse event that, had it occurred in a 
more severe form or was allowed to continue, might have caused death 
3. Requires or prolongs inpatient hospitalization 
4. Results in persistent or significant disability/incapacity (i.e., the adverse event results in 
substantial disruption of the subject’s ability to conduct normal life functions) 
5. Congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug 
6. Significant medical event in the Investigator's judgment (e.g., may jeopardize the subject or may 
require medical/surgical intervention to prevent one of the outcomes listed above) 
7. Encephalopathy of any grade (see Section 10.2.1) 
Death that is clearly the result of disease progression should be documented but should not be reported 
as an SAE. 
 


 
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8.6.2 
Overdose 
An overdose for bomedemstat will be defined as any dose of study drug(s) that is 10% or more over the 
prescribed dose per cycle as described in the study protocol. The investigator must notify the Principal 
Investigator of this event via pager within 24 hours of awareness (although not considered an SAE).  
No specific information is available on the treatment of overdose of bomedemstat. There is no specific 
antidote for bomedemstat overdose. In clinical studies, the highest total daily dose tested was 6 mg/kg/d. 
Aside from expected hematologic toxicities, no recurrent adverse events were noted up to the 6 mg/kg/d 
dose. The pharmacological effects may be prolonged after serum levels of active bomedemstat are no 
longer present. It is not known if bomedemstat is dialyzable. In the event of overdose, bomedemstat should 
be held and the patient should be observed closely for signs of toxicity. Appropriate supportive treatment 
should be provided as clinically indicated. 
8.6.3 
Pregnancy  
8.6.3.1 Maternal exposure 
If a patient becomes pregnant during study participation, bomedemstat will be discontinued immediately 
and permanently and the subject will be ineligible for further receipt of treatment in the study. 
Pregnancy itself is not regarded as an AE unless there is a suspicion that bomedemstat and/or 
atezolizumab may have interfered with the effectiveness of a contraceptive medication. Congenital 
abnormalities or birth defects and spontaneous miscarriages should be reported and handled as SAEs. 
Elective abortions without complications should not be handled as AEs. The outcome of all pregnancies 
(spontaneous miscarriage, elective termination, ectopic pregnancy, normal birth, or congenital abnormality) 
should be followed up and documented even if the patient was discontinued from the study. 
If any pregnancy occurs in the course of the study, then the Investigator or other site personnel should 
inform the Principal Investigator within 1 day, i.e. immediately, but no later than 24 hours of when he or she 
becomes aware of it. 
The designated study representative will work with the Investigator to ensure that all relevant information is 
provided to the sponsor approved Patient Safety data entry site within 1 to 5 calendar days for SAEs and 
within 30 days for all other pregnancies. 
The same timelines apply when outcome information is available. 
8.6.3.2 Paternal exposure 
Male patients should refrain from fathering a child or donating sperm during the study and for 30 days after 
the last dose of bomedemstat and 90 days after the last dose of atezolizumab, whichever is longer. 
Pregnancy of the patient’s partner is not considered to be an AE. However, the outcome of all pregnancies 
(spontaneous miscarriage, elective termination, ectopic pregnancy, normal birth, or congenital abnormality) 
occurring from the date of the first dose until 90 days after the last dose of study treatment, if possible, be 
followed up and documented. 
Where a report of pregnancy is received, prior to obtaining information about the pregnancy, the Investigator 
must obtain the consent of the patient’s partner. Therefore, the local study team should adopt the generic 
ICF template in line with local procedures and submit it to the relevant Ethics Committees (ECs)/Institutional 
Review Boards (IRBs) prior to use. 


 
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9.0 
CRITERIA FOR EVALUATION AND ENDPOINT ANALYSIS 
9.1 
Measurability of Lesions  
9.1.1 
Measurable disease 
Note that measurable disease is defined differently for malignant lymph nodes vs other disease as follows. 
Lesions other than malignant lymph nodes that can be accurately measured in at least one dimension 
(longest diameter to be recorded) as ≥ 2.0 cm by chest x-ray, by ≥ 1.0 cm with CT or MRI scans, or ≥ 1.0 
cm with calipers by clinical exam. All tumor measurements must be recorded in decimal fractions of 
centimeters (or millimeters).  
The defined measurability of lesions on CT scan is based on the assumption that CT slice thickness is 0.5 
cm or less. It is strongly recommended that CT slice of 0.5 cm be used. If CT scans have slice thickness 
greater than 0.5 cm, the minimum size for a measurable lesion should be twice the slice thickness.  
Malignant lymph nodes are to be considered pathologically enlarged and measurable if it measures ≥ 1.5 
cm in short axis (greatest diameter perpendicular to the long axis of the lymph node) when assessed by 
scan (CT scan slice recommended being no greater than 0.5 cm). 
9.1.2 
Non-measurable disease 
All other lesions (or sites of disease), including small lesions (longest diameter < 1.0 cm or pathologic lymph 
nodes with ≥ 1.0 cm to <1.5 cm short axis), are considered non-measurable disease. Bone lesions, 
leptomeningeal 
disease, 
ascites, 
pleural/pericardial 
effusions, 
lymphangitis 
cutis/pneumonitis, 
inflammatory breast disease, and abdominal masses (not followed by CT or MRI), are considered as non-
measurable as are previously radiated lesions that have not progressed. 
9.1.3 
Notes on measurability 
1. For CT and MRIs, the same type of scanner should be used and the image acquisition protocol 
should be followed as closely as possible to prior scans. It is no longer necessary to distinguish 
between spiral and conventional CT. 
2. Body scans should be performed with breath-hold scanning techniques, if possible.  
3. PET-CT:  At present, the low dose or attenuation correction CT portion of a PET-CT is not always 
of optimal diagnostic CT quality for use with RECIST measurements. However, if the site can 
document that the CT performed as part of a PET-CT is of identical diagnostic quality to a 
diagnostic CT, then the CT portion of the PET-CT can be used for RECIST measurements and 
can be used interchangeably with stand-alone CT. The slice thickness of 0.5 cm or less is highly 
recommended. If CT scans have slice thickness > 0.5 cm, the minimum size for a measurable 
lesion should be twice the slice thickness. 
4. Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement. 
5. Cystic lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they are, by 
definition, simple cysts. 
6. If a target lesion becomes very small some radiologists indicate that it is too small to measure. If 
the lesion is still present, a default measurement of 0.5 cm should be applied.  


 
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7. If the radiologist believes the lesion is no longer discernible, a default measurement of 0.0 cm 
should be recorded. 
9.2 
Objective Status at Radiographic Evaluation 
Objective Status is to be recorded at each evaluation. All measurable lesions up to a maximum of 2 lesions 
per organ, 5 lesions in total, representative of all involved organs, should be identified as target lesions at 
baseline. All other lesions (or sites of disease) including any measurable lesions over and above the 5 
target lesions should be identified as non-target lesions. Measurements must be provided for target 
measurable lesions, while presence or absence must be noted for non-target measurable and non-
measurable disease.  
For studies that use disease progression as an endpoint, all potential sites of metastases should be 
evaluated at each time point rather than following only sites of disease identified at baseline. It is acceptable 
to image only the areas of the body most likely to be involved with metastatic disease for the tumor type 
(chest, abdomen, pelvis, and/or bone scan are typical), with the addition of any areas with suspected 
involvement based upon clinical symptoms. For study-specific imaging requirements, see the Study 
Calendar in Section 7.0.  
9.2.1 
Complete Response (CR) 
Complete disappearance of all target and non-target lesions (with the exception of lymph nodes mentioned 
below). No new lesions. No disease related symptoms.  Any lymph nodes (whether target or non-target) 
must have reduction in short axis to < 1.0 cm. All disease must be assessed using the same technique as 
baseline. 
9.2.2 
Partial Response (PR) 
Applies only to participants with at least one measurable lesion. Greater than or equal to 30% decrease 
under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal 
progression of non-measurable disease. No new lesions. All target measurable lesions must be assessed 
using the same techniques as baseline. 
9.2.3 
Stable Disease 
Does not qualify for CR, PR, PD or Symptomatic Deterioration. All target measurable lesions must be 
assessed using the same techniques as baseline. 
9.2.4 
Progressive Disease / Disease Progression (PD) 
One or more of the following must occur:  
1. 20% increase in the sum of appropriate diameters of target measurable lesions over smallest 
sum observed (over baseline if no decrease during therapy) using the same techniques as 
baseline, as well as an absolute increase of at least 0.5 cm.  
2. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an 
explanation must be provided).  
3. Appearance of any new lesion/site (see Section 9.2.4.2 for details).  
4. Death due to disease without prior documentation of progression and without symptomatic 
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9.2.4.1 Confirmation of PD 
Unconfirmed disease progression is defined as a single disease assessment showing disease progression 
as defined above. Confirmed disease progression is defined as a second determination of progression at 
least 4 weeks after the initial report of progression.  
If the second assessment documents an absence of progression, the participant’s disease is deemed not 
to have progressed and the initial report of progression is coded as a pseudo-progression. If there are no 
additional disease assessments at least 4 weeks after the initial assessment documenting absence of 
progression (either due to inadequate or missing assessment) then the initial assessment will be coded as 
a progression. Any indication of progression (per the definition above) reported after the determination of 
pseudo-progression will be coded a progression and will not require a second assessment to confirm 
progression. 
9.2.4.2 Notes on new lesions 
If a new lesion is equivocal, for example because of its small size, continued therapy and follow-up 
evaluation will clarify if it represents truly new disease. If repeat scans confirm there is definitely a new 
lesion, then progression should be declared using the date of the initial scan. 
Regarding new lesions, FDG-PET imaging can complement regular scans in identifying new lesions 
according to the following algorithm:  
 
1. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of progression 
based on a new lesion. 
2. No FDG-PET at baseline and a positive FDG-PET at follow-up corresponding to a potential new 
site of disease must have a confirmation by anatomical assessment (e.g. CT, MRI, x-ray) as new 
site of disease to be considered progressive disease. In such a case, the date of progressive 
disease will be the date of the initial abnormal FDG-PET.  
9.2.5 
Relapse/Progression, Following Surgery 
Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation 
must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation 
of progression and without symptomatic deterioration. 
9.2.6 
Symptomatic Deterioration 
Global deterioration of health status requiring discontinuation of treatment without objective evidence of 
progression. Efforts should be made to obtain objective evidence of progression after discontinuation. 
9.2.7 
Assessment inadequate, objective status unknown 
Progression or symptomatic deterioration has not been documented, and one or more target measurable 
lesions have not been assessed or inconsistent assessment methods were used. 
9.2.8 
Objective status notes 
1. Non-measurable and non-target measurable disease do not affect Objective Status in 
determination of CR (must be absent; a participant who otherwise has a CR, but who has non-
measurable or non-target measurable disease present or not assessed, will be classified as 
having a PR). However, non-measurable and non-target lesions are included in determination of 
progression (if new sites of disease develop or if unequivocal progression occurs in the opinion of 
the treating physician).  


 
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2. An objective status of PR or stable cannot follow one of CR. Stable can follow PR only in the rare 
case that tumor increases too little to qualify as progression, but enough that a previously 
documented 30% decrease no longer holds. 
3. In cases for which initial flare reaction is possible (hypercalcemia, increased bone pain, erythema 
of skin lesions), objective status is not progression unless either symptoms persist beyond 4 
weeks or there is additional evidence of progression.  
4. Lesions that appear to increase in size due to presence of necrotic tissue will not be considered 
to have progressed.  
5. For bone disease documented on bone scan only, increased uptake does not constitute 
unequivocal progression. However, increase in the soft tissue component of a lesion as 
measured by CT or MRI would constitute progression. 
6. Appearance of new pleural effusions does not constitute unequivocal progression unless 
cytologically proven of neoplastic origin, since some effusions are a toxicity related to therapy or 
other medical conditions. Increase in the size of an existing effusion does not constitute 
unequivocal progression, since the fluid status of the participant could alter the size of the 
effusion.  
9.3 
Best Response (RECIST 1.1 criteria) 
This is calculated from the sequence of objective statuses. 
1. CR: Two or more objective statuses of CR a minimum of four weeks apart documented before 
progression or symptomatic deterioration. 
2. PR: Two or more objective statuses of PR or better a minimum of four weeks apart documented 
before progression or symptomatic deterioration, but not qualifying as CR. 
3. Unconfirmed CR: One objective status of CR documented before progression or symptomatic 
deterioration but not qualifying as CR or PR. 
4. Unconfirmed PR: One objective status of PR documented before progression or symptomatic 
deterioration but not qualifying as CR, PR or unconfirmed CR. 
5. Stable/no response: At least one objective status of stable/no response documented at least 6 
weeks after Registration and before progression or symptomatic deterioration, but not qualifying 
as anything else above. 
6. Increasing disease: Objective status of progression within 12 weeks of Registration, not qualifying 
as anything else above.  
7. Symptomatic deterioration: Objective status of symptomatic deterioration within 12 weeks of 
Registration, not qualifying as anything else above.  
8. Inadequate assessment, response unknown: Progression or symptomatic deterioration greater 
than 12 weeks after Registration and no other response category applies. 
9.4 
Performance Status  
Participants will be graded according to the ECOG Performance Status Scale. 
POINT  
DESCRIPTION 


 
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0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g., light housework, office work.  
2 
Ambulatory and capable of self-care but unable to carry out any work activities; up 
and about more than 50% of waking hours.  
3 
Capable of limited self-care, confined to bed or chair more than 50% of waking 
hours.  
4 
Completely disabled; cannot carry on any self-care; totally confined to bed or chair. 
9.5 
Dose-limiting Toxicity (DLT) Definition 
DLT to bomedemstat combined with atezolizumab is defined as the occurrence of any of the following 
toxicities by CTCAE 5.03 determined to be possibly, probably, or likely related to bomedemstat or 
atezolizumab occurring within 21 days of initiation of treatment. The specific events are:  
1. Grade 4 non-hematologic toxicity (not laboratory). 
2. Grade 3 non-hematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care. 
3. Any Grade 3 or Grade 4 non-hematologic laboratory value if: 
a. Medical intervention is required to treat the patient, or 
b. The abnormality leads to hospitalization 
4. Thrombocytopenia leading to clinically significant sequelae (i.e., a clinically significant bleeding 
event or the need for prophylactic transfusions).  
Note: Thrombocytopenia is defined for this purpose as a platelet count < 100x103/mcL. A 
clinically significant bleeding event is defined as an event that is life-threatening, cannot be 
controlled, and/or results in hemodynamic instability. Prophylactic transfusion is defined as 
platelet transfusion in the setting of a platelet count of < 10x103/mcL. 
5. Febrile neutropenia. 
6. Grade 5 toxicity. 
9.6 
Progression-Free Survival (PFS)  
From the date of registration to the date of first document of PD or symptomatic deterioration (as defined 
above), or death due to any cause. PFS for participants last known to be alive without report of progression, 
symptomatic deterioration, or death is censored at date of last contact.  
9.7 
Overall Survival (OS) 
Measured from the date of registration until death from any cause. OS for participants last known to be 
alive is censored at the date of last contact. 


 
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9.8 
Treatment Discontinuation Reasons (See Section 6.6) 
See Section 6.6. 
10.0 
STATISTICAL CONSIDERATIONS 
10.1 
Overview 
This study will be conducted as a single institution, single arm study as described in Section 6.1. Patients 
with newly diagnosed ES-SCLC undergoing induction therapy with platinum-etoposide and ICI will be 
treated with bomedemstat maintenance therapy in combination with standard of care maintenance 
atezolizumab until disease progression, unacceptable toxicity, or other treatment discontinuation reason. 
The primary objectives of this study are to evaluate the safety of bomedemstat in combination with 
maintenance atezolizumab and to evaluate the percentage of patients who are alive and free from disease 
progression at 6 months following the initiation of bomedemstat with atezolizumab.  
10.2 
Safety Evaluation 
The DLT assessment period is 21 days from initiation of treatment. The first 6 eligible patients who receive 
at least one dose of bomedemstat and atezolizumab with at least 21 days of follow-up (safety analysis 
population) will be closely monitored for toxicities. If more than 2 patients experience DLTs (see Section 
9.5), then the starting dose of bomedemstat for a given platelet count will be reduced by 0.1 mg. Otherwise, 
accrual will proceed as described in Section 10.3. If the dose is reduced, following 6 additional patients 
meeting the criteria to be assessed for DLTs, the same rules will apply (continue at dose if <3 patients with 
DLT and dose reduce by 0.1 mg if >2 with DLT). 
10.2.1 Stopping Rule for Encephalopathy 
Due to the previous association of LSD1 inhibitors with encephalopathy28, the occurrence of 
encephalopathy of any grade at any point during study participation will result in immediate study 
discontinuation and cessation of study treatment for all subjects. 
10.2.2 Stopping Rule for Recurrent Toxicity 
If four or more patients experience unacceptable toxicity requiring permanent cessation of study treatment, 
the study will be immediately discontinued, and study treatment will cease for all subjects. 
10.3 
Sample Size Justification and Analysis Plans 
The total accrual goal to this study is 34 eligible patients. Based on the IMPOWER133 study, we estimate 
that 35% of patients with ES-SCLC are alive and free from disease progression at 6 months after initiation 
of maintenance anti-PD(L)1 therapy. With 34 patients, this study design has 90% power to detect a 25% 
improvement in 6-month PFS rates (from 35 to 60%) using a 1-sided binomial test at the 5% level. The 
observation of 17 patients progression-free (i.e. alive without PD or symptomatic deterioration) at 6 months 
(a 50% rate) would be considered evidence to rule out a 35% 6-month PFS rate. With 34 patients, 
proportions can be estimated to within 17% with 95% confidence and any toxicity with at least 10% 
prevalence is likely to be observed with 97% confidence.  
Additional analyses will evaluate proportions (such as toxicity or response rates within subgroups) 
accompanied by 95% confidence intervals. Distributions for time-to-event outcomes (PFS, OS) will be 
evaluated using the method of Kaplan-Meier. For point estimates at landmark times, the associated 95% 


 
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confidence interval (CI) will be calculated using Greenwood’s formula and based on a log-log transformation 
applied on the survival function. 
10.4 
Study Duration 
Based on prior accrual to SCLC clinical trials at the Fred Hutchinson Cancer Center (previously Seattle 
Cancer Care Alliance), it is estimated that 34 patients can be accrued over 24 months.  
10.5 
Data and Safety Monitoring  
See Section 11.1. 
11.0 
STUDY MANAGEMENT 
All investigators on the protocol will receive formal training in the ethical conduct of human research. 
Institutional support of trial monitoring is provided in accordance with the Fred Hutchinson Cancer 
Center/University of Washington Cancer Consortium's data and safety monitoring plan. 
11.1 
Monitoring of the study  
Institutional support of trial monitoring will be in accordance with the Fred Hutch/University of Washington 
Cancer Consortium Institutional Data and Safety Monitoring Plan. Under the provisions of this plan, Fred 
Hutch Clinical Research Support coordinates data and compliance monitoring conducted by consultants, 
contract research organizations, or Fred Hutch employees unaffiliated with the conduct of the study. 
Independent monitoring visits occur at specified intervals determined by the assessed risk level of the study 
and the findings of previous visits per the institutional DSMP.  
In addition, protocols are reviewed as needed by the Consortium Data and Safety Monitoring Committee 
(DSMC), Fred Hutch Scientific Review Committee (SRC) and the Fred Hutch/University of Washington 
Cancer Consortium Institutional Review Board (IRB). The review committees evaluate accrual, adverse 
events, stopping rules, and adherence to the applicable data and safety monitoring plan for studies actively 
enrolling or treating patients. The IRB reviews the study progress and safety information to assess 
continued acceptability of the risk-benefit ratio for human subjects. Approval of committees as applicable is 
necessary to continue the study. The trial will comply with the standard guidelines set forth by these 
regulatory committees and other institutional, state, and federal guidelines.  
11.2 
Data Management  
The Principal Investigator, or her/his designees, will prepare and maintain adequate and accurate 
participant case histories with observations and other data pertinent to the study. Original source 
documents should be transcribed to Case Report Forms (CRFs) and used to analyze the study data. Source 
documents include hospital records, clinical charts, laboratory and pharmacy records, and recorded 
electronic data.  
All data required by the trial will be entered onto paper and electronic case report forms. Any required 
corrections to data on paper case report forms must be made in such a way that the original entry is not 
obscured. Only designated study staff will enter data for study participants after study visits. Case report 
forms will be checked against source document data by study staff. Patient records will be kept in a secure 
location at the Fred Hutchinson Cancer Center accessible only to research authorized personnel. The 
patient identity will be kept as confidential as possible as required by law. Except as required by law, the 
patient will not be identified by name, social security number, address, telephone number, or any other 
direct personal identifier. Study subjects will be assigned an ID code. Information about the code will be 
kept in a secure location and access limited to research study personnel. The results of this research study 


 
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may be presented at scientific or medical meetings or published in scientific journals. However, the patient 
identity will not be disclosed. The patient's personal data which may be included in the investigator's 
database shall be treated in compliance with all applicable laws and regulations.  
12.0 
ETHICAL CONSIDERATIONS 
The study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and are consistent with ICH/Good Clinical Practice, and applicable regulatory requirements.  
The protocol will be approved and reviewed by the Cancer Consortium Scientific Review Committee (SRC) 
and the Institutional Review Board (IRB). Once activated, the protocol will be reviewed at least annually by 
both institutional entities.  
The protocol, the proposed informed consent and all forms of participant information related to the study 
(e.g., advertisements used to recruit participants) will be reviewed and approved by the Cancer Consortium 
IRB and SRC. Any changes made to the protocol will be submitted as a modification and will be approved 
by the IRB prior to implementation.  
Trial oversight will be carried out by the Principal Investigator, Dr. Rafael Santana-Davila, and his research 
staff, who will be qualified by education, training and experience to perform their respective tasks. Services 
of personnel for whom sanctions have been invoked for scientific misconduct or fraud will not be used. They 
will meet weekly to review recently acquired data and adverse events. The data recorded within the 
research charts and protocol database is compared with the actual data that is available from the medical 
record and/or clinical histories. Data detailed in the research case report forms includes the nature and 
severity of all toxicities, which are also reported as described above. 
13.0 
ABBREVIATIONS 
Abbreviation 
Full term 
CR 
Complete response 
DLT 
Dose-limiting toxicity 
DSMP 
Date safety monitoring plan 
ES 
Extensive stage disease 
ICI 
Immune checkpoint inhibitor, i.e. monoclonal antibody targeting the PD-1/PD-L1 signaling 
axis 
KDM1A 
Lysine-specific demethylase 1A (preferred gene symbol for the gene LSD1) 
LS 
Limited stage disease 
LSD1 
Lysine-specific demethylase 1 
PD 
Progressive disease (also referred to as "disease progression") 
PFS 
Progression-free survival 
PR 
Partial response 
SCLC 
Small cell lung cancer 
SD 
Stable disease 
 
14.0 
BIBLIOGRAPHY 
1 
Kalemkerian, G. P. et al. Small cell lung cancer. J Natl Compr Canc Netw 11, 78-98 (2013). 


 
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2 
Iams, W. T., Porter, J. & Horn, L. Immunotherapeutic approaches for small-cell lung cancer. Nat 
Rev Clin Oncol 17, 300-312, doi:10.1038/s41571-019-0316-z (2020). 
3 
Horn, L. et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung 
Cancer. N Engl J Med 379, 2220-2229, doi:10.1056/NEJMoa1809064 (2018). 
4 
Paz-Ares, L. et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line 
treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-
label, phase 3 trial. Lancet 394, 1929-1939, doi:10.1016/S0140-6736(19)32222-6 (2019). 
5 
Paz-Ares, L. G. et al. Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-
stage SCLC (ES-SCLC): Updated Results from the phase III CASPIAN study. J Clin Oncol 38, 
doi:10.1200/JCO.2020.38.15_suppl.9002 (2020). 
6 
Ready, N. E. et al. Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small 
Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort. J Thorac Oncol 15, 426-
435, doi:10.1016/j.jtho.2019.10.004 (2020). 
7 
Trigo, J. et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a 
single-arm, open-label, phase 2 basket trial. Lancet Oncol 21, 645-654, doi:10.1016/S1470-
2045(20)30068-1 (2020). 
8 
Poirier, J. T. et al. New Approaches to SCLC Therapy: From the Laboratory to the Clinic. J Thorac 
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15.0 
APPENDIX 
15.1 
VALG Staging Details  
Participants must have Extensive Stage (ES) SCLC as defined in the Veterans Administration Lung Study 
Group (VALG) staging system as follows: 
Stage 
Characteristics 
Limited 
 
7. Disease 
confined to one 
hemithorax, 
although local 
extensions 
may be 
present; and 
8. No 
extrathoracic 
metastases 
except for 
possible 
ipsilateral,  
9. supraclavicular 
nodes if they 
can be 
included in the 
same portal as 
the primary 
tumor; and 
10. Primary tumor 
and regional 
nodes that can 
be adequately 
treated and 
totally 
encompassed 
in every portal 
Extensive 
11. Inoperable 
patients who 
cannot be 
classified as 
having limited 
disease 
12. NOTE: limited 
stage patients 
who develop 


 
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disease 
progression 
during or 
following 
completion of 
definitive 
chemoradiation 
are considered 
to have 
extensive 
stage disease