Conditions: Mesothelioma
Keywords: Immunotherapy Checkpoint Inhibitor anti CTLA-4
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 2
Healthy volunteers: no

Brief summary:
Background:

Mesothelioma is a type of cancer. It originates in cells that line human body cavities. Most people have advanced disease when they are diagnosed. Researchers want to see if a combination of drugs can help.

Objective:

To find a safe dose of LMB-100 in combination with ipilimumab when LMB-100 is injected into tumors.

Eligibility:

Adults ages 18 and older with malignant pleural or peritoneal mesothelioma, that cannot be cured with surgery and has not responded to standard first-line treatments for mesothelioma.

Design:

Participants will be screened with:

* Tumor biopsy or effusion, if needed
* Medical history
* Physical exam
* Blood and urine tests
* Imaging scans
* Heart and lung function tests
* Pregnancy test, if needed

Some screening tests will be repeated during the study.

Participants will get LMB-100 on Days 1 and 4 for up to 2 cycles. Each cycle lasts 21 days. They will stay in the hospital for about 8 days each time they get LMB-100. It will be injected into their tumor with needles.

Participants will get ipilimumab through a tube that is put in a vein. It will be given on Day 2 of the first 2 cycles and Day 1 of the next 2 cycles.

Participants will be assessed for how well they do daily activities. They will give blood and tissue samples for research.

Participants will have a safety visit 4 to 6 weeks after the last dose of the study drugs. Then they will have scans every 6 weeks until their disease gets worse. If their tumor gets bigger, they will have phone, video, or email follow-ups every 12 weeks.

Participants will be on this study for life....

Detailed description:
Background:

LMB-100, and a closely related immunotoxin, SS1P, also targeting mesothelin, given intravenously, have been studied in Phase 1 clinical studies for mesothelioma and pancreatic cancer.

LMB-100 given intravenously results in systemic inflammation in patients, but as a single agent has limited anti-tumor efficacy.

Almost all patients develop neutralizing anti-LMB-100 antibodies after 2 cycles of therapy.

Intra-tumoral delivery of LMB-100 has been shown to induce immune cell infiltration in immune-competent mice, bearing murine malignant mesothelioma tumors. Combination with cytotoxic T-lymphocyte associated protein 4 (CTLA-4) blockage eradicates murine tumors by promoting anti-cancer immunity.

Ipilimumab is a fully human anti CTLA-4 monoclonal antibody, that is approved for treatment of melanoma and in combination with nivolumab for many solid tumors.

It is hypothesized that intra-tumoral delivery of anti-mesothelin immunotoxin LMB-100 in combination with ipilimumab will result in greater anti-tumor efficacy in patients with mesothelioma.

Objective:

To determine the safety and feasibility of intra-tumoral LMB-100 injection plus ipilimumab infusion in patients with mesothelioma

To identify the recommended phase 2 dose (RP2D) of intratumorally administered LMB-100 + ipilimumab in patients with malignant mesothelioma

Eligibility:

Histologically confirmed pleural or peritoneal mesothelioma not amenable to potentially curative surgical resection.

Have locally accessible disease suitable for intra-tumor injection of LMB-100. This includes superficial or visceral lesions.

Subjects must have received prior immune checkpoint therapy with anti-Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with anti-CTLA4 blocking antibodies, as well as platinum-based chemotherapy.

Age \>= 18 years.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Adequate organ and bone marrow function

Subjects with clinically significant pericardial effusion are excluded.

Chemotherapy within 3 weeks or radiotherapy within 2 weeks prior to start of study therapy, is prohibited.

Subjects with active central nervous system (CNS) metastasis are excluded.

Subjects with active autoimmune disease for which they have received systemic immunosuppressive medications during the previous 2 years (excluding daily glucocorticoid-replacement therapy for conditions such as adrenal or pituitary insufficiency) are excluded.

Subjects with active interstitial lung disease, or a history of pneumonitis or interstitial lung disease for which they had received glucocorticoids are excluded.

Design:

This is an open-label, single center phase I dose escalation study of intratumorally administered LMB-100 followed by ipilimumab in subjects with malignant mesothelioma.

Subjects will receive intratumorally administered LMB-100, beginning at dose level 1, in 21-day cycles. LMB-100 will be given on days 1 and 4 of cycle 1, and ipilimumab is given on day 1 of cycles 2-4.

Tumor biopsies will be performed prior to each administration of LMB-100, on day 1 of cycle 2 and after completion of ipilimumab therapy to evaluate changes in the tumor immune microenvironment.

Up to 14 evaluable subjects will be enrolled.

Arms:
arm 1: Those with pleural or peritoneal mesothelioma receiving intra-tumoral administration of LMB-100 + ipilimumab for up to 4 cycles.

Interventions: intervention 1: LMB-100 intervention 2: ipilimumab intervention 3: Diphenhydramine intervention 4: Famotidine intervention 5: Acetaminophen intervention 6: Dexamethasone intervention 7: Biopsy intervention 8: FDG-PET intervention 9: CT CAP intervention 10: MRI intervention 11: ECG intervention 12: Echocardiogram
Intervention descriptions: intervention 1: LMB-100 administered into lesion on days 1 and 4 during cycle 1. intervention 2: Administered intravenously once per cycle up to three 21-day cycles. Administration will occur during cycles 2,3,4. intervention 3: Infusion related reactions precaution: All participants will be premedicated with 25-50 mg Diphenhydramine by mouth (PO) or intravenous (IV) (or alternative antihistamine at adequate dose) 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration. intervention 4: Infusion related reactions precaution: All participants will be premedicated with 20 mg Famotidine by mouth (PO) or intravenous (IV) (or alternative histamine H2- receptor antagonists (H2) blocker at adequate dose) 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration. intervention 5: Infusion related reactions precaution: All participants will be premedicated with 650 mg Acetaminophen by mouth (PO) or intravenous (IV) 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration. intervention 6: Additional infusion precaution at infusions of LMB-100 after Cycle 1 Day 1 (as appropriate): Dexamethasone 20 mg by mouth (PO), 6-12 hours prior to LMB-100 administration OR 10mg, intravenous (IV), 30-60 minutes prior to LMB-100 administration OR equivalent dose of another corticosteroid as clinically indicated. intervention 7: As feasible at screening, Cycle 1 Day 1 and 5, Cycle 2, 3, \& 4 Day 1, and Cycle 4 Day 21 (±7 days). intervention 8: At screening, at the end of cycles 2 \& 4 ± 7 days, Follow-Up Visit (4-6 weeks after end of treatment), and Long-Term Follow-Up (every 6-12 weeks). intervention 9: At screening, at the end of cycles 2 \& 4 ± 7 days, Follow-Up Visit (4-6 weeks after end of treatment), and Long-Term Follow-Up (every 6-12 weeks). intervention 10: At screening, at the end of cycles 2 \& 4 ± 7 days, Follow-Up Visit (4-6 weeks after end of treatment), and Long-Term Follow-Up (every 6-12 weeks). intervention 11: At screening, Cycle 1 Day 1, Cycles 2, 3, \& 4 Day 1 and Follow-Up Visit (4-6 weeks after end of treatment). intervention 12: At screening.

Protocol document:
Prot_SAP_000.pdf: 
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ICF_001.pdf: 
IRB NUMBER: 000059
IRB APPROVAL DATE: 5/30/2023
PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (1)
Version Date: 04/24/2023
Page 1 of 20
CC ICF template v. 05.05.20
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
PRINCIPAL INVESTIGATOR:
Raffit Hassan, M.D.
STUDY TITLE:
Phase I Study of Intratumor Injection of anti-Mesothelin 
Immunotoxin LMB-100 with Ipilimumab in Malignant 
Mesothelioma
STUDY SITE:
NIH Clinical Center
Cohort:
Affected Participants 
Consent Version:
04/24/2023
WHO DO YOU CONTACT ABOUT THIS STUDY? 
Raffit Hassan, M.D. by phone at 240-760-6232 or email raffit.hassan@nih.gov 
KEY INFORMATION ABOUT THIS RESEARCH 
This consent form describes a research study and is designed to help you decide if you would 
like to be a part of the research study. 
You are being asked to take part in a research study at the National Institutes of Health (NIH). 
This section provides the information we believe is most helpful and important to you in making 
your decision about participating in this study. Additional information that may help you decide 
can be found in other sections of the document. Taking part in research at the NIH is your choice.
You are being asked to take part in this study because you have malignant mesothelioma that 
cannot be cured by surgery and which was unsuccessfully treated with the standard 
chemotherapy and immunotherapy for this disease.
The purpose of this study is to find a safe dose of LMB-100, an agent that targets the mesothelin 
on your tumor cells, in combination with ipilimumab, a drug that helps your immune system to 
fight against your cancer. LMB-100 will be injected directly into your tumor.
LMB-100 has not been approved by the US Food and Drug Administration (FDA) for the 
treatment of any disease. Ipilimumab is approved in combination with nivolumab for the 
treatment of multiple cancers, including pleural mesothelioma. Therefore, the use of the drugs 
in this study is investigational as a combination of LMB-100 and ipilimumab has not been 
approved.  However, the FDA has given us permission to use LMB-100 in combination with 
ipilimumab in this study.
There are other drugs that may be used to treat your disease, and these can be prescribed/given 
by your regular cancer doctor, even if you are not in this study. The way in which treatment is 
given in this study and the side effects are different than if you were to receive standard care. 
Although the treatment is given directly in the tumor, we hope that killing of the tumor cells by 


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LMB-100 will stimulate your immune system to attack tumor cells not only at the sites of LMB-
100 injection but also at other un-injected tumor sites. Administration of ipilimumab could 
stimulate the immune response generated by LMB-100 injection to make it more effective 
against the tumor. There could be side effects due to local injection of LMB-100 as well other 
sites in the body.
If you decide to join this study, here are some of the most important things that you should know 
that will happen:

You will be evaluated to find out if you are a suitable candidate for this study. This will 
involve having standard blood and urine tests, scans, tests of your heart and lung function 
and a confirmation of your diagnosis which would involve providing us a sample of your 
tumor. This can be an existing sample or if one is not available, we would collect one 
from you. 

LMB-100 will be injected into your tumor(s) on days one and four of one 21-day cycle. 
You will have to stay in the hospital for about 8 days each time you receive LMB-100. 
Your study doctor will decide what type of anesthesia you need for the procedure. At 
minimum, there will be a local anesthetic (like lidocaine) placed on the areas where the 
needles will be injected. To receive LMB-100, a needle will be inserted in one or 
multiple points in your tumor(s), using an ultrasound or CT scan to guide the needle. 

Ipilimumab will be given for up to three cycles. It will be given through a tube inserted 
in one of your veins on day 1 of cycles 2, 3 and 4.

If your disease gets worse or you have side effects that are intolerable, the study drugs 
may be stopped sooner.

You will be seen regularly during the study. You will have clinical, laboratory, and 
imaging tests to see how you are doing and to assess your disease. We will also collect 
required samples from you (such as: blood and tumor tissue).

You must use effective birth control methods and try not to become pregnant while 
participating in this study and for at least four months after the last dose of study 
treatment.

You may experience side effects from taking part in this study. Some can be mild or very 
serious, temporary, long-lasting, or permanent, and may include death. Examples of 
some of the side effects that you may have include side effects of the study drugs such 
as kidney damage, leaky blood vessels, allergic reactions, itchiness, watery stools and 
inflammation of various organs. You will also be exposed to radiation from the CT 
guided injection procedure described above. 

After the study treatment has ended, we will see you in the clinic for a safety checkup 
4-6 weeks after your last dose of study drug. After the safety-checkup, if your disease 
has not gotten worse while on study, we would like to see you every 6 weeks so we can 
perform scans. If your tumors do increase in size at any point, the follow up assessments 
will be done every 12 weeks and will consist of a phone or video call or email to find 
out how you are doing, whether you are having side effects and if you have started any 
new cancer treatment. This assessment will continue for the rest of your life.
We do not know if you may benefit from taking part in this study. If you do not benefit, this 
study and the results from our research will help others in the future.


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You are free to stop participating in the trial at any time. If you decide to stop, the study doctor 
may ask you to agree to certain tests to make sure it is safe for you to stop.
The remaining document will now describe the research study in more detail. This information 
should be considered before you make your choice. Members of the study team will talk with you 
about the information in this document. Some people have personal, religious, or ethical beliefs 
that may limit the kinds of medical or research treatments they would want to receive (such as 
blood transfusions). Take the time you need to ask any questions and discuss this study with NIH 
staff, and with your family, friends, and personal health care providers.
If the individual being asked to participate in this research study is not able to give consent for 
themselves, you, as the Legally Authorized Representative, will be their decision-maker and you 
are being asked to give permission for this person to be in this study. For the remainder of this 
document, the term “you” refers to you as the decision-maker and/or the individual being asked to 
participate in this research. 
IT IS YOUR CHOICE TO TAKE PART IN THE STUDY
You may choose not to take part in this study for any reason. If you join this study, you may change 
your mind and stop participating in the study at any time and for any reason. In either case, you 
will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you 
must be taking part in a study or are being considered for a study. If you do choose to leave the 
study, please inform your study team to ensure a safe withdrawal from the research. 
WHY IS THIS STUDY BEING DONE?
This is a research study. The purpose of this research study is to find a safe dose of LMB-100 
injected into your tumors.
We are asking you to join this research study because you have malignant pleural or peritoneal 
mesothelioma that cannot be cured with surgery and which has not responded to the standard first 
line treatments given for mesothelioma.
LMB-100 has not been approved by the US Food and Drug Administration (FDA) for the treatment 
of any disease. Ipilimumab is approved in combination with nivolumab for the treatment of 
multiple cancers, including pleural mesothelioma. Therefore, the use of the drugs in this study is 
investigational as a combination of LMB-100 and ipilimumab has not been approved.  However, 
the FDA has given us permission to use LMB-100 in combination with ipilimumab in this study 
for your mesothelioma. We are testing it in this research study to see if LMB-100 can be given 
safely in combination with ipilimumab when LMB-100 is directly injected into your tumors. We 
are also interested in finding out whether the combination might cause your tumors to shrink or 
allow you to live longer with or without tumors.
WHAT WILL HAPPEN DURING THE STUDY?
Before you begin the study 
Before beginning the study, you will need to undergo tests and/or procedures to help your doctor 
verify whether you can participate. This is called screening. Most of the exams, tests, and 


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procedures you will have are part of the usual approach for your cancer. However, there are some 
extra procedures that you will need to have if you take part in this study. If you have already 
undergone some of these examinations very recently, your doctor may decide not to repeat them. 
Briefly, these tests, which may be performed under a separate protocol, include:

Confirmation of diagnosis (You must provide a sample of tumor tissue for an evaluation 
by the NCI Laboratory of Pathology. The tissue may be from a previous surgery, biopsy or 
collection from a tumor effusion (fluid around the tumor). If none is available, we will ask 
you to have a biopsy or a collection of effusion material to provide a fresh sample). Please 
see page12, Tumor Biopsies and Effusions for a description of the procedure.

Medical history and physical examination

Routine blood (4 – 5 teaspoons) and urine tests including pregnancy test in women who 
can have children. Pregnant women will not be allowed on this study.

CT scan or MRI, and PET scans – to allow us to see your tumor(s)

Electrocardiogram (ECG) – which test the electrical activity of your heart

Echocardiogram – which uses soundwaves (like an ultrasound) to test the functioning of 
your heart

Hepatitis B and C testing (~2 teaspoons)

HIV testing (~ 1 teaspoon)
As part of this study, we will test you for infection with the human immunodeficiency virus 
(HIV), the virus that causes AIDS.  If you are infected with HIV you will not be able to 
participate in this study.  We will tell you what the results mean, how to find care, how to 
avoid infecting others, how we report HIV infection, and the importance of informing your 
partners at possible risk because of your HIV infection.
Your Responsibilities
You will need to follow the study team’s instructions and plan to attend all required study visits
Before you are given ipilimumab, tell your healthcare provider about all your health problems if 
you: 

have an active condition where your immune system attacks your body (autoimmune 
disease), such as ulcerative colitis, Crohn’s disease, lupus, or sarcoidosis 

had an organ transplant, such as a kidney transplant 

have liver damage from diseases or drugs 

have any other medical conditions 

are pregnant or plan to become pregnant. 

are breastfeeding 
Tell your study doctor about all the medicines you take, including all prescription and non-
prescription medicines, steroids or other medicines that lower your immune response, vitamins, 
and herbal supplements. Please also let your study doctor know about any vaccinations you plan 
to receive. 


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There are some types of medications and vaccines that you will need to avoid while you are 
receiving study therapy. 
Study Drugs
If you decide to take part in this study, once we know that you are eligible LMB-100 will be given 
directly into your tumors through needles on days 1 and 4 of one 21-day cycle as described in the 
key information section. You will have to stay in the hospital for about 8 days each time you 
receive LMB-100. LMB-100 will be injected into each lesion gradually. The time it takes will 
depend on the size of the tumor, but it will be no more than a few minutes. You will receive 
medications to help manage pain during these injections.

This will include a shot at the site of collection (local anesthesia) which numbs the area. 

You may also undergo conscious sedation which is usually given during minor surgical 
procedures to relax participants and minimize discomfort.  It can be given as a pill, a shot, 
an IV or even inhaled. You may have to wait up to an hour to start feel the effects depending 
on how it is given. Once it takes effect, you will be mostly awake, though relaxed or 
drowsy.  You will be monitored throughout the procedure for any changes to your breathing 
and blood pressure.

You may receive general anesthesia which involves a combination of medications (inhaled 
and/or given through an IV drip) that puts you in a sleep-like state before surgery or other 
medical procedure.  You will not feel pain as you will be completely unconscious. While 
you're under anesthesia, the anesthesiologist monitors your body's vital functions and 
manages your breathing through a tube inserted into your mouth and down your windpipe.  
The tube will also protect your lungs from blood and other fluids. 
You will receive medication before each dose of LMB-100 to help prevent side effects. These 
medications include an antihistamine (such as Benadryl), a histamine 2 blocker (such as Pepcid) 
and acetaminophen (Tylenol). Participants who have a reaction after any dose of LMB-100 will 
also receive a steroid, such as dexamethasone before the remaining LMB-100 doses.
After each dose of LMB-100, your vital signs (blood pressure, pulse, temperature, oxygen levels) 
will be monitored for at least 5 hours. 
Ipilimumab will be given for up to three cycles. It will be given through a tube inserted in one of 
your veins (IV) on day 1 of cycles 2, 3 and 4. After each dose of ipilimumab, we will monitor your 
vital signs for up to an hour. 
We will continue to check vital signs while you remain in the hospital.
Assessments While Receiving the Study Drugs
During the study, you will have certain clinical procedures performed so that we can assess your 
health and find out if the study drugs are having an effect on your tumor.
These tests/procedures include the following:
(Some tests which may have already been done during the screening process may not need to be 
repeated on day 1 of cycle 1)


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Performed once before you receive any study drugs

Test of certain markers on your immune cells
Performed daily while hospitalized during cycle 1, then on day 1 of the next three cycles

Medical history and physical exam including weight and vital signs (pulse, temperature, 
blood pressure, etc.)
Performed only on day 1 of each cycle

Routine urine tests

Assessment of how well you perform daily activities

Pregnancy test if you are woman who can have children 

ECG (electrocardiogram) 
Performed on days 1, 3, 5, 8 and 15 of the first cycle and on day 1 of the next three cycles

Routine blood tests (up to 12 teaspoons at each collection, no more than 1.5 cups over 8 
weeks)
Performed every 2 cycles (or every 6 weeks)

CT scans or MRIs of your tumors

FDG PET scans of your tumors
In addition to the above tests that we will conduct to determine whether you are having side effects 
or if you are responding to the study therapy, we will also collect samples from you for purposes 
of research only. The samples are being collected to look at how your body processes the study 
drugs, how your immune system reacts to the study drugs and how the presence of certain markers 
such as mesothelin or affect your response to the study drugs. We will also collect samples to find 
out which genes are expressed both before and after treatment. Gene expression is the when the 
information stored in our DNA is converted into instructions for making proteins or other 
molecules. This process allows a cell to respond to its environment. We are interested to know if 
the study therapy changes the environment around the tumor. 
The samples included for these studies include:

Blood samples will be collected on day 1 of each cycle on days 4 and 7 of cycle 1 and after 
your last dose of study therapy. These will include serial collections of blood before and 
for up to four hours after your LMB-100 injection. 

Tissue samples collected with the tumor injection if feasible (days 1 and 4 of the first cycle, 
day 1 of the second cycle and after you have finished your last dose of ipilimumab). The 
tumor samples are collected exclusively for research purposes and will not benefit you. It 
might help other people in the future. You will be given the opportunity to decide whether 
you want to have these samples collected at the time of each biopsy/effusion collection. As 
your tumor collection during the first  cycle will be done at the same time that we are 
injecting your tumor(s) with study drug, the drugs used to manage pain for those injections 
will be the same drugs used to manage pain during the biopsy.  After cycle 1, we will only 
use local anesthesia or conscious sedation for pain management.


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After You Have Finished Taking the Study Drugs
Safety follow up
We will need to see you for a safety visit 4- 6 weeks after you have taken your last dose of study 
therapy. At this visit, we will take a medical history and perform a physical exam. We will collect 
blood for routine blood tests and perform a pregnancy test if you are woman who can have children 
CT scans or MRIs, and FDG-PET scans to monitor your disease will be performed if your tumors 
have not grown up to this point. We may also collect the end of treatment research blood sample 
(about three quarters of teaspoon) if we were unable to collect one the end of therapy. 
Long Term-Follow Up
We will continue to perform scans every 6 weeks until your disease gets worse. If you are unable 
to come to the NIH Clinical Center for these scans, you may have them done at a local center and 
send them to us. Your study team can instruct you on how. We may also contact you by phone, 
email or video chat (remotely) to speak with you directly and find out how you are doing. Once 
your tumors have started to grow, you will no longer be scanned. However, we will be in touch 
remotely every 12 weeks for the rest of your life, so we can find out how you are doing, what 
medications you are taking and if you are experiencing any side-effects. 
HOW LONG WILL THE STUDY TAKE?
If you agree to take part in this study, your involvement is expected to last for the rest of your life 
as described in the key information section and the section above. 
HOW MANY PEOPLE WILL PARTICIPATE IN THIS STUDY?
We plan to have about 14 people participate in this study at the NIH. 
WHAT ARE THE RISKS AND DISCOMFORTS OF BEING IN THE STUDY?
If you choose to take part in this study, there is a risk that the study drugs may not be as good as 
the standard drugs available for treatment of your cancer at shrinking or stabilizing your tumor.
There is also a risk that you could have side effects from the study drugs and study procedures. 
These side effects may be worse and may be different than you would get with the usual approach 
for your cancer. Some of these side effects may become serious or life-threatening, and in some 
cases, may lead to death.
You also may have the following discomforts:

Spend more time in the hospital or doctor’s office.

Be asked sensitive or private questions about things you normally do not discuss.

May not be able to take part in future studies. 
Risks and Possible Undesirable Effects of LMB-100
LMB-100 has only been given to a limited number of subjects; therefore, we do not know all of 
the possible side effects. In addition, to this point, we have only given LMB-100 by IV route. 
However, below is a list of the most common and most serious side effects occurring on our earlier 
studies, some occurring at higher doses than will be used in this study.


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Possible Side Effects of LMB-100
COMMON, SOME MAY BE SERIOUS
In 100 people receiving LMB-100, more than 20 and up to 100 may have:

Low levels of the blood protein albumin which may lead to swelling, muscle weakness 
or loss of appetite

Tiredness

Swelling localized to some part of the body, such as the arms and legs, face

Anemia, which may require a blood transfusion

Low blood pressure which may cause you to feel faint

Increase blood level of creatinine (a substance normally eliminated by the kidneys into 
urine)

Muscle pain

Increased blood levels of liver enzymes

Nausea 

Shortness of breath

Decreased number of a type of white blood cell

Decreased blood level of sodium which can cause headaches, confusion, seizures, 
fatigue or coma

Weight gain

Fever

Abnormally fast heartbeat, with regular or irregular rhythm
OCCASIONAL, SOME MAY BE SERIOUS
In 100 people receiving LMB-100, from 4 to 20 may have:

Decreased appetite

Infection, especially when white blood cell count is low

Bruising, bleeding due to decreased number of type of blood cell

Vomiting

Dizziness

Fluid in the organs which may cause low blood pressure, shortness of breath, swelling 
of ankles

Hair loss

Pain, including belly pain


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OCCASIONAL, SOME MAY BE SERIOUS
In 100 people receiving LMB-100, from 4 to 20 may have:

More protein leaking into the urine than usual, often a sign of kidney disease

Headache

Reactions during or following the infusion of the drug which may cause fever, chills, 
rash or low blood pressure

Abnormal laboratory results

Fluid around the heart that can lead to a life-threatening condition where the heart is 
unable to pump correctly due to external pressure. We would need to drain the fluid 
around the heart to relieve the pressure. 

Numbness, tingling or pain in the arms and legs

Fluid around the lungs

Joint pain

Chest pain, not heart related

Kidney damage which may cause swelling and may require dialysis

Increased blood level of a heart muscle protein indicating damage to the heart muscle

Chills

Constipation

Increased blood level of enzyme from muscle

Dehydration

Diarrhea

Decreased oxygen supply to the tissue
RARE, AND SERIOUS
In 100 people receiving LMB-100, fewer than 4 may have:
A condition in which there is muscle breakdown or injury that may lead to kidney damage 
that may have been caused by LMB-100. People experiencing this condition may notice 
muscle pain or dark red urine and may have abnormal results in laboratory tests for 
muscle. 
Inflammation in membranes around your heart or lungs causing chest pain, shortness of 
breath, low blood pressure, and heart failure.
Inflammation of the heart muscle
As with other drugs similar to LMB-100, there is a chance that the drug could cause the body to 
produce an unwanted response called ‘Anti-drug antibodies’ (ADAs). These might not cause 
problems however there is a chance they could lead to a severe anti-drug response in the body. 
ADA levels will be measured during the study to monitor any changes as part of the research on 
this study.


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Risk of Giving LMB-100 Directly into the Tumor 
In addition to the risks of radiation from the use of CT scans to guide our injections addressed 
above, risks of this procedure include pain and fever lasting 1-4 days. If the pain is severe, we will 
need to give you pain medications intravenously. Although rare, there is also a possibility, that 
while injecting the drug into the tumor we could injure the normal lung leading to air around the 
lungs or injure the bowels. There may also be reddening around the injection site. Anesthesia will 
be provided as needed. 
You may feel pain at the injection sites(s)
Risks of Ipilimumab
Common side-effects (occurring 5 or more of every 10 patients receiving ipilimumab): 

Fatigue 

Diarrhea

Itching

Rash

Stomach pains
Less common but potentially life-threatening side-effects: 
As noted above, ipilimumab works by helping your immune system to fight your cancer. However, 
ipilimumab can also lead to autoimmune disease where your immune system attacks normal organs 
and tissues in your body and can affect the way they work This can cause:

Inflammation of the intestines (colitis) that can cause tears or holes (perforation) in the 
intestines. Signs and symptoms of colitis may include: 
o
diarrhea (loose stools) or more bowel movements than usual 
o
blood in your stools or dark, tarry, sticky stools 
o
stomach pain (abdominal pain) or tenderness 

Inflammation of the liver (hepatitis) that can lead to liver failure. Signs and symptoms of 
hepatitis may include: 
o
yellowing of your skin or the whites of your eyes 
o
dark urine (tea colored) 
o
nausea or vomiting 
o
pain on the right side of your stomach 
o
bleeding or bruise more easily than normal 

Inflammation of the skin that can lead to severe skin reaction (toxic epidermal necrolysis). 
Signs and symptoms of severe skin reactions may include: 
o
skin rash with or without itching 
o
sores in your mouth 
o
your skin blisters and/or peels 


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
Inflammation of the nerves that can lead to paralysis. Symptoms of nerve problems may 
include: 
o
unusual weakness of legs, arms, or face 
o
numbness or tingling in hands or feet 

Inflammation of hormone glands (especially the pituitary, adrenal, and thyroid glands) that 
may affect how these glands work. Signs and symptoms that your glands are not working 
properly may include: 
o
persistent or unusual headaches 
o
unusual sluggishness, feeling cold all the time, or weight gain 
o
changes in mood or behavior such as decreased sex drive, irritability, or 
forgetfulness 
o
dizziness or fainting 

Inflammation of the eyes. Symptoms may include: 
o
blurry vision, double vision, or other vision problems 
o
eye pain or redness 

Inflammation in other organs (e.g., lungs, pancreas, kidneys, heart)
Other less common side-effects include: 

Infusion reaction, including dizziness or fainting (low blood pressure), flushing, rash, 
fever, shortness of breath or sick to your stomach, or pain at the site of infusion. Although 
usually reversible with treatment, it can be severe or life threatening.
What Are the Risks Related to Pregnancy?
If you are able to become pregnant, we will ask you to have a pregnancy test before starting this 
study. You will need to practice an effective form of birth control before starting study treatment, 
during study treatment, and for four months after you finish study treatment (the restricted period). 
If you become pregnant, there may be unknown risks to the fetus or unborn child, or risks that we 
did not anticipate. There may be long-term effects of the treatment being studied that could 
increase the risk of harm to a fetus. You must tell the study doctor if your birth control method 
fails during the restricted period. If you think or know you have become pregnant during the 
restricted period, please contact the study team as soon as possible.
If you are a sexually active person with a partner able to become pregnant, it is important that your 
partner not become pregnant during the restricted period. There may be unknown risks to a fetus 
or risks we did not anticipate. You and your partner must agree to use birth control if you want to 
take part in this study. If you think your partner has become pregnant during the restricted period, 
please contact the study team as soon as possible. If you and your partner plan for your partner to 
become pregnant after the restricted period, please discuss this with the study team.
What Are the Risks of Radiation from Being in the Study? 
During your participation in this research study, you will be exposed to radiation from nine CT 
scans, five CT guided tumor injections and biopsies and nine FDG-PET scans each year. The 


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amount of radiation you will receive from these procedures is equal to approximately19.3 rem. A 
rem is a unit of absorbed radiation.
Every day, people are exposed to low levels of radiation that come from the sun and the 
environment around them. The average person in the United States receives a radiation exposure 
of 0.3 rem per year from these sources. This type of radiation is called “background radiation”. 
This study will expose you to more radiation than you get from everyday background radiation. 
No one knows for sure whether exposure to these low amounts of radiation is harmful to your 
body.
The CT scans (including those for the biopsies) and FDG PET scans that you get in this study will 
expose you to roughly the same amount of radiation as 64.3 years’ worth of background radiation. 
Being exposed to too much radiation can cause harmful side effects such as an increase in the risk 
of cancer. The risk depends on how much radiation you are exposed to. Please be aware that about 
40 out of 100 people (40%) will get cancer during their lifetime, and 20 out of 100 (20%) will die 
from cancer. The risk of getting cancer from the radiation exposure in this study is 1.9 out of 100 
(1.9%) and of getting a fatal cancer is 1.0 out of 100 (1.0%).
You may not participate in this study if you are pregnant. If you are able to become pregnant, we 
will perform a pregnancy test before exposing you to radiation. You must tell us if you may have 
become pregnant within the previous 14 days because the pregnancy test is unreliable during that 
time.
What Are the Risks from the Study Procedures?
Many of the interventions you will undergo during the study are not associated with any significant 
risk or discomforts aside from possible breaches of confidentiality. These include urine collection, 
echocardiograms, ECGs, physical examination and collection of your medical information.
However, the following study procedures and treatments may have risks and cause discomfort 
while you participate on this study:
Blood draws
There is the risk of slight pain, bruising or infection when your blood is drawn. Drawing blood 
may cause some people to faint. Including both routine and research blood collections, no more 
than 5 tablespoons of blood will be collected at single timepoint and up to a little over 1.5 cups 
may be collected over a given 8-week period.
Tumor Biopsies and Effusions 
Tumor biopsies and tumor effusions: local anesthesia of the skin will be given prior to any tumor 
biopsy or effusion collection, in order to prevent painful sensations. However, you may still 
experience pain or discomfort at the biopsy site. Irritation, redness, swelling and/or bleeding may 
also occur. There is a risk of abnormal healing, fever or infection. Once the sample has been 
obtained, a stitch may be used to close the wound and facilitate healing.
Anesthesia
Local anesthesia
You may experience an allergic reaction that can include itching and hives. 


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Conscious Sedation
Potential side effects of conscious sedation include headache, nausea, slow reflexes, low blood 
pressure, loss of memory of what happened during the procedure and drowsiness. These side 
effects usually go away quickly.
General Anesthesia
Potential side effects of general anesthesia include temporary confusion and memory loss, 
dizziness, difficulty passing urine, muscle aches, itching, bruising or soreness from the IV drip, 
nausea, and vomiting, shivering and feeling cold, and sore throat due to the breathing.
CT Scans and PET scans
In addition to the radiation risks from the scans discussed above, you may experience an allergic 
reaction to the dye we inject into your veins to help us view the scan better. You might experience 
hives, itching, headache and water retention. More serious reactions that would include difficulty 
breathing, increased heartrate and swelling of your throat or other body parts. 
MRIs
People are at risk for injury from the MRI magnet if they have some kinds of metal in their body. 
You will be screened before each MRI scan to determine if you might have metal in your body. If 
you have a question about metal in your body, you should inform the staff. 
If you have a fear confined spaces or have back problems, you might experience anxiety or 
discomfort during the MRI. 
The noise from the scanner is loud enough to damage hearing, especially in people who already 
have hearing loss. Everyone having a research MRI scan will be fitted with hearing protection. If 
the hearing protection comes loose during the scan, you should let us know right away.
During part of the MRI, you may receive gadolinium, a contrast agent, through an intravenous (iv) 
catheter.
It is not known if MRI with contrast is completely safe for a developing fetus. Therefore, all 
women of childbearing potential will have a pregnancy test performed no more than 24 hours 
before each MRI scan with contrast. The scan will not be done if the pregnancy test is positive. 
The risks of an IV catheter include bleeding, infection, or inflammation of the skin and vein with 
pain and swelling. 
Mild symptoms from gadolinium infusion occur in fewer than 1% of those who receive it and 
usually go away quickly. Mild symptoms may include coldness in the arm during the injection, a 
metallic taste, headache, and nausea. In an extremely small number, fewer than one in 300,000 
people, more severe symptoms have been reported including shortness of breath, wheezing, hives, 
and lowering of blood pressure. You should not receive gadolinium if you previously had an 
allergic reaction to it. You will be asked about such allergic reactions before gadolinium is given.
People with kidney disease are at risk for a serious reaction to gadolinium contrast called 
“nephrogenic systemic fibrosis (NSF)”. This condition always involves the skin and can also 
involve the muscles, joints and internal organs. NSF has resulted in a very small number of deaths. 
A blood test of your kidney function may be done within the month before an MRI scan with 


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gadolinium contrast. You will not receive gadolinium for a research MRI scan if your kidney 
function is below the safe level.
Most of the gadolinium contrast leaves the body in the urine. However, the FDA has issued a safety 
alert that indicates small amounts of gadolinium may remain in the body for months to years.  The 
long-term effects of gadolinium retention are unknown. At this time, retained gadolinium has not 
been linked to health risks in people whose kidneys work well. Some types of gadolinium contrast 
drugs are less likely to remain in the body than others. In this study, we will use the gadolinium 
contrast drugs that are less likely to remain in the body. We will also give you additional 
information called a “Medication Guide.” Upon request, we will give you individual information 
about retained gadolinium we see on your studies. 
WHAT ARE THE BENEFITS OF BEING IN THE STUDY?
You might not benefit from being in this study. 
However, the potential benefit to you might be shrinking of your tumor or decrease in your 
symptoms, such as pain, that are caused by the cancer. Because there is not much information 
about the drug’s effect on your cancer, we do not know if you will benefit from taking part in this 
study.
Are There Any Potential Benefits to Others That Might Result from the Study?
In the future, other people might benefit from this study because what we learn in this study may 
eventually be used to treat others with your disease.
WHAT OTHER OPTIONS ARE THERE FOR YOU?
Before you decide whether or not to be in this study, we will discuss other options that are 
available to you. Instead of being in this study, you could:

choose to be treated with surgery, radiation or with drugs already approved by the FDA for 
your disease

choose to take part in a different study if one is available

choose not to be treated for cancer but you may want to receive comfort care to relieve 
symptoms.
DISCUSSION OF FINDINGS
New Information About the Study
If we find out any new information that may affect your choice to participate in this study, we 
will get in touch with you to explain what we have learned. This may be information we have 
learned while doing this study here at the NIH or information we have learned from other 
scientists doing similar research in other places.
Return of Research Results
The results of the standard tests performed as part of the research are available to you as part of 
your medical record. We do not plan to return the results of your research only tests to you.


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EARLY WITHDRAWAL FROM THE STUDY 
Your doctor may decide to stop your therapy for the following reasons:

if he/she believes that it is in your best interest

if your disease gets worse during treatment (after confirmed by a second scan) 

if you have side effects from the treatment that your doctor thinks are too severe

if you require medication that is not permitted on this study

if new information shows that another treatment would be better for you

if you become pregnant

if you do not follow the study rules

if the study is stopped for any reason
In this case, you will be informed of the reason therapy is being stopped. 
After therapy is stopped, we would like to see you for a safety visit 4 – 6 weeks after your last 
dose.
You can stop taking part in the study at any time. However, if you decide to stop taking part in the 
study, we would like you to talk to the study doctor and your regular doctor first.
If you decide at any time to withdraw your consent to participate in the trial, we will not collect 
any additional medical information about you.
STORAGE, SHARING AND FUTURE RESEARCH USING YOUR SPECIMENS AND 
DATA
Will your specimens or data be saved by the study team for use in other studies?
As part of this study, we are obtaining specimens and data from you. We plan to store and use 
these specimens and data for studies other than the ones described in this consent form that are 
going on right now, as well as studies that may be conducted in the future. The specimens and 
data will be kept in a way that we will still know that they came from you (i.e., they will be 
identifiable to us). If we use your identifiable specimens or data for future research, our study 
will be reviewed and approved by an Institutional Review Board who will make sure that we are 
protecting your confidentiality. These future studies might help us better understand 
mesothelioma, or other diseases or conditions. This could include studies to develop other 
research tests, treatments, drugs, or devices, that may lead to the development of a commercial 
product by the NIH and/or its research or commercial partners. There are no plans to provide 
financial compensation to you if this happens. Also, it is unlikely that we will learn anything 
from these studies that may directly benefit you.
I give permission for my identifiable specimens and data to be stored and used by the study team 
for future studies as described above.
_____ Yes
_____ No
Initial
Initial


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Will your specimens or data be shared with other researchers for use in other studies?
We may share coded specimens and data with other researchers. The other researchers may be 
doing studies in similar areas to this study or in other unrelated areas. These researchers may be 
at NIH, other research centers and institutions, or at commercial entities.
If we do share your specimens or data, we will know that the specimens and data came from you. 
However, the other researchers will not know that they came from you (i.e., they will be de-
identified).  
I give permission for my de-identified specimens and data to be shared with and used by other 
researchers for future studies.
_____ Yes 
_____ No
Initial
Initial
In some cases, it may help other researchers to know that the specimens or data were collected 
from you (i.e., they will have your identifiers). If we share your identity with other researchers, 
their study will be reviewed and approved by an Institutional Review Board who will make sure 
that the study team is protecting your confidentiality. 
I give permission for my identifiable specimens and data to be shared with and used by other 
researchers for future studies.
_____ Yes 
_____ No
Initial
Initial
In addition to the planned use and sharing described above, we might remove any labels from your 
specimens and data that might identify you (i.e., anonymize them), and use them or share them 
with other researchers for future studies at the NIH or other places.  When we or the other 
researchers use your anonymized specimens and data for these projects, there will be no way to 
know that they came from you. We want to make sure that you understand that this is a possibility 
if you participate in this study. Once we do this, we would not be able to remove your specimens 
or data from these studies or prevent their use in future studies because we would not be able to 
tell which specimens or data belong to you.
Can you change your mind about use and sharing for future research?
If you change your mind and do not want us to store and use your specimens and data for future 
studies, you should contact the study team. We will do our best to comply with your request but 
cannot guarantee that we will always be able to destroy your specimens and data. For example, 
if some research with your specimens and data is already complete, the information from that 


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research may still be used. Also, if the specimens and data have been shared already, it might 
not be possible to withdraw them. 
How long will your specimens and data be stored by the NIH?
Your specimens and data may be stored by the NIH indefinitely. 
Risks of storage and sharing of specimens and data
When we store your specimens and data, we take precautions to protect your information from 
others that should not have access to it. When we share your specimens and data, we will do 
everything we can to protect your identity, for example, when appropriate, we remove information 
that can identify you. Even with the safeguards we put in place, we cannot guarantee that your 
identity will never become known, or that no one will gain unauthorized access to your 
information. New methods may be created in the future that could make it possible to re-identify 
your specimens and data.
COMPENSATION, REIMBURSEMENT, AND PAYMENT
Will You Receive Compensation for Participation in the Study?
Some NIH Clinical Center studies offer compensation for participation in research. The amount 
of compensation, if any, is guided by NIH policies and guidelines.
You will not receive compensation for participation in this study. 
Will You Receive Reimbursement or Direct Payment by NIH As Part of Your Participation?
Some NIH Clinical Center studies offer reimbursement or payment for travel, lodging or meals 
while participating in the research. The amount, if any, is guided by NIH policies and guidelines.
On this study, the NCI will cover the cost for some of your expenses. Some of these costs may be 
paid directly by the NIH and some may be reimbursed after you have paid. The amount and form 
of these payments are determined by the NCI Travel and Lodging Reimbursement Policy.  You 
will be given a summary of the policy which provides more information.
Will Taking Part in This Research Study Cost You Anything? 
NIH does not bill health insurance companies or participants for any research or related clinical 
care that you receive at the NIH Clinical Center. 

If some tests and procedures are performed outside the NIH Clinical Center, 
you may have to pay for these costs.
CONFLICT OF INTEREST (COI) 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest. This process is detailed in a COI Guide. You may ask your research team for a copy 
of the COI Guide or for more information. Members of the research team who do not work for 
NIH are expected to follow these guidelines or the guidelines of their home institution, but they 
do not need to report their personal finances to the NIH.
No NIH investigator involved in this study receives payments or other benefits from any company 
whose drug, product or device is being tested.


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CLINICAL TRIAL REGISTRATION AND RESULTS REPORTING 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time.
CONFIDENTIALITY PROTECTIONS PROVIDED IN THIS STUDY 
Some of your health information, and/or information about your specimen, from this study will 
be kept in a central database for research. Your name or contact information will not be put in 
the database. Your test results will be identified by a unique code and the list that links the code 
to your name will be kept separate from your sample and health information. Your information 
may be given out if required by law. For example, certain states require doctors to report to health 
boards if they find a disease like tuberculosis. However, the researchers will do their best to 
make sure that any information that is released will not identify you.
Will Your Medical Information Be Kept Private?
We will do our best to make sure that the personal information in your medical record will be kept 
private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy 
your medical records for research, quality assurance, and data analysis include:

The NIH and other government agencies, like the Food and Drug Administration (FDA), 
which are involved in keeping research safe for people.

National Institutes of Health Intramural Institutional Review Board

The study Sponsor, Center for Cancer Research, NCI, or their agents
The researchers conducting this study and the NIH follow applicable laws and policies to keep 
your identifying information private to the extent possible. However, there is always a chance that, 
despite our best efforts, your identity and/or information about your participation in this research 
may be inadvertently released or improperly accessed by unauthorized persons.
In most cases, the NIH will not release any identifiable information collected about you without 
your written permission. However, your information may be shared as described in the section of 
this document on sharing of specimens and data, and as further outlined in the following sections. 
Further, the information collected for this study is protected by NIH under a Certificate of 
Confidentiality and the Privacy Act. 
Certificate of Confidentiality
To help us protect your privacy, the NIH Intramural Program has received a Certificate of 
Confidentiality (Certificate). With this certificate, researchers may not release or use data or 
information about you except in certain circumstances. 
NIH researchers must not share information that may identify you in any federal, state, or local 
civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a 
court. 
The Certificate does not protect your information when it: 


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1. is disclosed to people connected with the research, for example, information may be used 
for auditing or program evaluation internally by the NIH; or 
2. is required to be disclosed by Federal, State, or local laws, for example, when information 
must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA); 
3. is for other research;
4. is disclosed with your consent. 
The Certificate does not prevent you from voluntarily releasing information about yourself or your 
involvement in this research. 
The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or 
others including, for example, child abuse and neglect, and by signing below you consent to those 
disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice 
and Acknowledgement of Information Practices consent.
Privacy Act
The Federal Privacy Act generally protects the confidentiality of your NIH medical information 
that we collect under the authority of the Public Health Service Act. In some cases, the Privacy 
Act protections differ from the Certificate of Confidentiality. For example, sometimes the Privacy 
Act allows release of information from your record without your permission, for example, if it is 
requested by Congress. Information may also be released for certain research purposes with due 
consideration and protection, to those engaged by the agency for research purposes, to certain 
federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect 
reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is 
involved in a lawsuit. However, NIH will only release information from your medical record if it 
is permitted by both the Certificate of Confidentiality and the Privacy Act.
POLICY REGARDING RESEARCH-RELATED INJURIES 
The NIH Clinical Center will provide short-term medical care for any injury resulting from your 
participation in research here. In general, no long-term medical care or financial compensation for 
research-related injuries will be provided by the NIH, the NIH Clinical Center, or the Federal 
Government. However, you have the right to pursue legal remedy if you believe that your injury 
justifies such action.
PROBLEMS OR QUESTIONS
If you have any problems or questions about this study, or about your rights as a research 
participant, or about any research-related injury, contact the Principal Investigator, Raffit Hassan, 
M.D., Raffit.Hassan@nih.gov, 240-760-6232. You may also call the NIH Clinical Center Patient 
Representative at 301-496-2626, or the NIH Office of IRB Operations at 301-402-3713, if you 
have a research-related complaint or concern.
CONSENT DOCUMENT 
Please keep a copy of this document in case you want to read it again.


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Adult Research Participant: I have read the explanation about this study and have been given the opportunity 
to discuss it and to ask questions. I consent to participate in this study.
Signature of Research Participant
Print Name of Research Participant
Date
Legally Authorized Representative (LAR) for an Adult Unable to Consent: I have read the explanation 
about this study and have been given the opportunity to discuss it and to ask questions. I am legally authorized 
to make research decisions on behalf of the adult participant unable to consent and have the authority to provide 
consent to this study. As applicable, the information in the above consent was described to the adult participant 
unable to consent who agrees to participate in the study.
Signature of LAR
Print Name of LAR
Date
Investigator:
Signature of Investigator
Print Name of Investigator
Date
Witness should sign below if either:
1. A short form consent process has been used to enroll a non-English speaking subject or
An oral presentation of the full consent has been used to enroll a blind or illiterate subject
Signature of Witness*
Print Name of Witness
Date
*NIH ADMINISTRATIVE SECTION TO BE COMPLETED REGARDING THE USE OF AN 
INTERPRETER:
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent and served as a witness. The investigator obtaining consent may not 
also serve as the witness.
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent but did not serve as a witness. The name or ID code of the person 
providing interpretive support is:
.