Clinical trial NCT02810418
Conditions: Neoplasms Pancreatic Neoplasms
Keywords: Immunotoxin Mesothelin Antibody-based Therapeutics Advanced Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2016-08-03; Completion date: 2021-06-22
Enrollment: 40 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Background:

LMB-100 is a man-made protein designed to kill cancer cells. LMB-100 targets a cancer marker called mesothelin. Mesothelin is found on the surface of many different tumors, including pancreatic cancer, but is made by a very small number of normal tissues. Other cancers that make mesothelin include mesothelioma, cholangiocarcinoma, thymic carcinoma, ovarian, lung, gastric, endometrial, cervical, and ampullary cancers. After binding to the mesothelin on tumors, LMB-100 can attack and kill cancer cells. Researchers want to see how well it works when given with and without nab-paclitaxel, a drug which treats pancreatic cancer.

Objectives:

Arm A- To find a safe dose of LMB-100 with a fixed standard dose of nab-paclitaxel in people with advanced pancreatic cancer. To see how well the combination of the two drugs reduce tumor size.

Arm B- To find a safe dose of LMB-100 when it is given as a continuous infusion over several days.

Eligibility:

Arm A- Adults age 18 and older with advanced pancreatic cancer that has worsened after anti-cancer therapy.

Arm B- Adults age 18 and older with advanced pancreatic cancer, mesothelioma or other solid tumor that makes mesothelin that has worsened after anti-cancer therapy

Design:

Participants will be screened with medical history and physical exam. They will give blood, urine, and tissue samples. They will have scans and x-rays.

During each 21-day cycle:

* For Arm A

  * Participants will get LMB-100 by an intravenous (IV) catheter on days 1, 3, and 5. This is a tube inserted in a vein, usually in the arm.
  * Participants will get nab-paclitaxel by IV on days 1 and 8.
* For Arm B

  * Participants will get LMB-100 by an IV catheter as a continuous infusion beginning on day 1 and continuing for 2-4 days
  * Some participants will also get nab-paclitaxel by IV on days 1 and 8.

All participants will get this combination for up to 2 cycles or until their disease worsens or they have intolerable side effects.

Participants will have blood and urine tests and scans throughout the study.

Participants will have a safety follow-up visit 3-6 weeks after treatment ends. If their disease remains stable or improves, they will be scanned every 6 weeks until their disease gets worse. Even if their disease gets worse, they or their doctor will be called to talk about their cancer status....

Detailed description:
Background:

* Pancreatic cancer is the fourth most common cause of cancer death in the United States, claiming more than 40,000 lives each year.
* Incidence nearly equals mortality with just 6% of participants living five years beyond their diagnosis. Most patients are diagnosed at an advanced stage, but even patients with early stage disease have a long term survival of less than 20%.
* Mesothelin is specifically a marker of adenocarcinoma in the human disease and is not expressed in preceding pre-malignant stages of tumor development
* Expression of mesothelin in pancreatic ductal adenocarcinoma (PDA) has been examined in several published studies and ranges from 86 to 100%
* Recombinant immunotoxins (RITs) are antibody-based therapeutics that carry a toxin payload. RITs that target mesothelin contain a genetically engineered variant of Pseudomonas exotoxin A (PE) in which the native cell-binding domain of PE is replaced by the mesothelin-binding antibody fragment. SS1P was the first mesothelin-targeted RIT tested in patients.
* LMB-100 contains a newly engineered PE fragment that has improved activity against most pancreatic cancer cell lines in vitro, and is also much less toxic than SS1P in preclinical models. The new PE contains modifications specifically designed to reduce immunogenicity of the molecule.
* Pre-administration of paclitaxel with SS1P was demonstrated to increase the amount of immunotoxin internalized by tumor cells and to reduce levels of shed mesothelin in the intra-tumoral environment so that more immunotoxin could bind tumor cells. The effect is even more pronounced with NAB-paclitaxel in a pancreatic cancer model.
* Initial clinical testing of LMB-100 was performed by Roche in a multi-center international first in human trial (NCT02317419). The agent was well tolerated and appeared to have decreased immunogenicity compared to SS1P based on preliminary results.
* In initial and subsequent clinical testing, LMB-100 was found to have half-life of approximately 60 mins. This is shorter then that measured for previous RITs used in the clinical setting.

Primary Objectives:

* Arm A1 (Phase I, short infusion):

  --To determine the maximum tolerated dose of short infusion LMB-100 in combination nab-paclitaxel chemotherapy in participants with advanced pancreatic cancer
* Arm B1(Continuous infusion single agent lead-in):

  --To determine the maximum tolerated dose of LMB-100 given in a continuous infusion format over 24 - 96 hours to patients with advanced solid tumors that express mesothelin
* Arm B2 (Continuous infusion combination therapy)

  --Establish a tolerated dose of LMB-100 given by continuous infusion in combination with nab-paclitaxel chemotherapy in participants with advanced pancreatic cancer
* Arm A2 (Phase II, short infusion):

  * To determine the objective response rate (Partial Response (PR)+Complete Response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria of short infusion LMB-100 in combination with nab-paclitaxel chemotherapy in participants with advanced pancreatic cancer

Eligibility:

* Age greater than or equal to18 years
* Histologically confirmed recurrent, metastatic and/or advanced pancreatic ductal adenocarcinoma (Except for Arm B1 \[B Single Agent Lead-in\])
* For Arm B1 (Single Agent Lead-in), ONLY: Histologically confirmed solid tumor malignancy for which no curative therapy exists with at least 25% of tumor cells expressing mesothelin as determined by National Cancer Institute (NCI) Laboratory of Pathology. Determination can be made using archival tumor tissue or fresh biopsy.
* Treatment must include at least one prior chemotherapy regimen
* No nab-paclitaxel or paclitaxel treatment in the last four months (Except for Arm B1 \[Single Agent Lead-in\])
* Adequate organ function
* Participants with human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections are eligible only for the Arm B1 (Single Agent Lead-in)

Design:

* This study is a Phase I/II open label study to assess the safety and efficacy of LMB-100 in combination with the standard of care agent nab-paclitaxel in participants metastatic and/or locally advanced pancreatic ductal adenocarcinoma
* Subjects will be treated for up to 2 cycles
* In Arm A1 (Phase I, short infusion) of the study, up to 3 dose levels will be evaluated. LMB-100 will be administered on days 1, 3 and 5 of a 21 day cycle and nab-paclitaxel will be administered on days 1 and 8
* Arm A2 (Phase II, short infusion), up to 20 evaluable participants (including those treated at the short infusion maximum tolerated dose (MTD) in the phase I study) will be enrolled.
* Arm B1 (Continuous infusion single Agent Lead-in), escalating doses of single agent LMB-100 will be administered. The study drug will be given as a continuous infusion for the 1, 2, 3, or 4 days of a 21-day cycle.
* Arm B2 (Continuous infusion, combination therapy) will be initiated after completion of both Arm A1 and Arm B1 Single Agent Lead-in. It will test a single dose level of LMB-100 based on data from the Lead-in given in combination with nab-paclitaxel. LMB-100 will be given as a continuous infusion for the 1, 2, 3 or 4 days of a 21-day cycle. Nabpaclitaxel will be given on Day 1 and Day 8.
* The Arm A2 (Phase II, short infusion) portion of the study will be conducted in a Simon Minimax two stage phase II design. The first stage will enroll 13 evaluable participants, including the six participants treated at the short infusion MTD from phase I. If 1 or more has a response, then accrual would continue until a total of 20 evaluable participants have been enrolled.

Arms: arm 1: Arm A1, Dose Level 1, Phase I Short Infusion 100µg/kg LMB-100 +125mg/m\^2 nab-paclitaxel

Dose level 1 (DL1) Maximum tolerated dose (MTD) determination in patients with pancreatic cancer receiving short infusion LMB-100+nabpaclitaxel arm 2: Arm A1, DL-1, Ph I Short Infusion 65µg/kg LMB-100 +125mg/m\^2 nab-paclitaxel arm 3: Arm A2, Phase 2 Short Infusion 65µg/kg LMB-100 +125mg/m\^2 nab-paclitaxel

Efficacy determination in patients with pancreatic cancer receiving short infusion LMB-100 + nabpaclitaxel arm 4: Arm B1, DL2, 48-hr Continuous Infusion Single Agent Lead-in 100µg/kg/day LMB-100 Maximum tolerated dose (MTD) determination in patients with pancreatic cancer receiving continuous infusion LMB-100 as single agent arm 5: Arm B1, DL1, 48-hr Continuous Infusion Single Agent Lead-in 65µg/kg/day LMB-100 arm 6: Arm B1, DL3R, 24-hr Continuous Infusion Single Agent Lead-in 100µg/kg LMB-100 arm 7: Subjects with pancreatic cancer receiving continuous infusion LMB-100 combination therapy
Interventions: intervention 1: LMB-100 intervention 2: Nab-Paclitaxel intervention 3: Mesothelin Expression intervention 4: LMB-100
Intervention descriptions: intervention 1: Arms A1 and A2 (short infusion): Administered intravenously (IV) on days 1, 3 and 5 of a 21 day cycle for a maximum of 2 cycles Arm B1 (continuous infusion): Administered IV for 24, 48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 21 day cycle for a maximum of 2 cycles. Arm B2 (continuous infusion): Administered IV for 24,48, 72 or 96 hours continuously on the first 1 - 4 days or 24 hour infusions on days 1 and 4 (depending on dose level) of each 14 day cycle for a maximum of 3 cycles. intervention 2: Administered intravenously (IV) on days 1 and for Arms A1, A2 and B1 on day 8 of each 14-21 day cycle for a maximum of 2 (Arms A1, A2 and B1) or 3 (Arm B2) cycles intervention 3: Research blood test for Arm B1 eligibility intervention 4: A 40 mcg/kg loading dose of LMB-100 is administered over 30 minutes immediately prior to the start of each long infusion.

Protocol documents:
ICF_005.pdf: 
MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
16-C-0128 
PRINCIPAL INVESTIGATOR: 
Christine Alewine, M.D., Ph.D. 
STUDY TITLE:  
A Phase I/II Study of Mesothelin-Targeted Immunotoxin LMB-100 Alone or in 
Combination with Nab-Paclitaxel in Participants with Previously Treated Metastatic and/ 
or Locally Advanced Pancreatic Ductal Adenocarcinoma and Mesothelin Expressing 
Solid Tumors 
 
Continuing Review Approved by the IRB on 08/31/20 
Amendment Approved by the IRB on 12/13/18 (L) 
 
Date posted to web: 09/04/20   
Arm B2 (Continuous infusion combination therapy) 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent (4) 
 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary.  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
You may receive no benefit from taking part.  The research may give us knowledge that 
may help people in the future. 
Second, 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).  If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
Now we will describe this research study.  Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional.   
Why is this study being done?  
LMB-100 is an investigational agent, meaning that it has not been approved by the US Food and 
Drug Administration. It is a type of manufactured protein which is similar to protein normally 
produced by your body.  LMB-100 is attracted to the mesothelin protein, which is present on the 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 2 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
surface of many different tumors, including many, but not all, pancreatic cancers. The 
mesothelin protein is found in only a very small number of normal tissues.  After binding to the 
mesothelin on tumors, LMB-100 can then attack and kill cancer cells.  
Nab-paclitaxel is an FDA approved agent in the treatment of pancreatic cancer. It has not, 
however been tried in combination with LMB-100. 
This study, which is divided into multiple parts will determine a safe dose of LMB-100 on 
different administration schedules alone or in combination with a fixed dose of nab-paclitaxel in 
the phase 1 portion. 
x In phase 1, Arm A1 – subjects with pancreatic cancer will receive nab-paclitaxel in 
combination with LMB-100 given every other day for 3 days in each 21-day cycle.  
x In phase 1, Arm B1, (single Agent lead-in) – subjects that have tumors that test positive 
for mesothelin will receive LMB-100 alone for 1 or 2days continuously or two 24-hour 
infusions (days 1 and 4) depending on dose level in each 21-day cycle. 
x In phase 1, Arm B2, (combination therapy) – subjects with pancreatic cancer will receive 
nab-paclitaxel in combination with LMB-100 given for 24 hours continuously on day 1 
of each 14-day cycle.  
In the phase 2 portion of the study (Arm A2), we will determine whether the dose established in 
phase 1, Arm A1 reduces the size of tumors in patients with pancreatic cancer.  
You are part of Arm B2 (combination therapy). 
Why are you being asked to take part in this study? 
You are being asked to take part in this study because you have advanced pancreatic cancer that 
has worsened after anti-cancer therapy.  
How many people will take part in this study?  
Up to 100 participants will be enrolled in the study overall. 
Description of Research Study 
Based on the results from Arm B1, you will receive LMB-100 through an IV catheter (a tube 
inserted in a vein, usually in your arm though, as stated below in During the Study, it may be 
placed in a different location if your doctor feels it is necessary) continuously for 24 hours on 
day 1 of each 14-day cycle. You will have to stay in the hospital while you are receiving the 
LMB-100 infusion.  Nab-paclitaxel will also be given by IV on days 1 of each 14-day cycle. You 
will receive LMB-100 in combination with nab-paclitaxel for up to 3 cycles or until your disease 
worsens or you have intolerable side effects, whichever happens first. We will continue to follow 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 3 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
you after you have finished taking the study drug to keep track of your disease status 
(progression), your survival status or whether you have taken any additional cancer therapy.  The 
specific procedures you will have are described below. 
What will happen if you take part in this research 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 
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 are performed under a separate consent, include: 
x Confirmation of diagnosis (You must provide a sample tumor tissue for formal evaluation 
by the NCI Laboratory of Pathology.  The tissue may be from a previous surgery or 
biopsy.  If none is available, we will ask you to have a biopsy to provide a fresh sample).   
x Medical history and physical examination 
x Routine blood and urine tests including pregnancy test in women who can have children.  
Pregnant women will not be allowed on study. 
x Scans 
x Electrocardiogram (ECG) 
x Echocardiogram 
x Tests for viruses (hepatitis and HIV) 
x Blood for tumor markers 
During the study 
Once it is determined that you are eligible and you have signed the consent for the study, you 
will receive IV infusions of LMB-100 and nab-paclitaxel as described above. Each LMB-100 
infusion will last for 24 hours (1 day) and will be given through a central line (an IV tube placed 
in a large vein for long term therapy) or through a mediport if you already have one installed. 
Each nab-paclitaxel infusion lasts about 30 minutes. You will receive the LMB-100 about 30 
minutes after you have completed the nab-paclitaxel infusion.  You will be monitored for side 
effects during each LMB-100 infusion.  You will be given standard pre-medications that include 
an antihistamine (such a Benadryl), acetaminophen (Tylenol) and ranitidine to help prevent 
infusion related side effects. Dexamethasone or an equivalent steroid may be added if you 
experience a reaction even after using the standard pre-medications. 
While you are taking study medication, we will perform a number of tests and examinations for 
safety and to test the effect of the study therapy: 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 4 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
These include routine blood and urine tests that will be on each day you receive an infusion, 
scans that will be performed approximately every 6 weeks, and ECGs that will be done while 
you are receiving LMB-100. 
In addition to the safety tests, we will also perform tests for research studies to find out how your 
body handles the drugs (PKs), how your body, including your immune system, reacts to the drug 
and how certain side effects of the LMB-100 might be caused. We will also conduct genetic 
studies focused on genes that process drugs, nab-paclitaxel in particular.  Most of the sampling 
for these research tests will be done before your first dose of study drug or on the days you take 
the study drug just before or during the infusion.  In addition, on day 1 of cycle 1 samples will be 
drawn before your infusion and periodically for up to 72 hours (3 days) after the end of your nab-
paclitaxel infusion. 
An optional biopsy may also be collected after you have received 2 cycles of study therapy.  The 
biopsies to be performed are 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 sample collected at the time of each biopsy.  All tissue will be reviewed by the NCI 
Laboratory of Pathology. Please see page 9, Tumor Biopsies and Effusions for the risks of a 
biopsy. 
When you are finished taking the drugs 
Withdrawal Visit 
If you received 3 cycles of LMB-100, the following assessments will be performed at the end of 
cycle 3: 
x Medical history and physical examination 
x Routine blood and urine tests 
x Scans 
x Blood tests for tumor markers 
x ECG 
Safety Visit 
If you did not complete all cycles of the study drug, or if you have completed 3 cycles but the 
scans above showed that your disease has gotten worse, you will be asked to return to the NIH 
approximately 3 – 6 weeks after you have had last dose of study drug for a safety visit.  
If you completed cycle 3 and your scans did not reveal worsening disease, you will be asked to 
return approximately six weeks after your last scan for a restaging scan and safety visit. 
The visit will include the following tests: 
x Medical history and physical exam 
x Routine blood and urine tests including pregnancy test in women who can have children 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 5 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
x ECG 
x Scans if your disease has not worsened since the beginning of the study 
Long term follow up 
If after the safety visit, your disease remains stable or improved, you will continue to be scanned 
every 6 weeks until your disease gets worse. 
About once a year, regardless of whether your disease has gotten worse, we will contact you or 
your physician by telephone to ask about any other cancer therapies you may have started and 
about your survival status. 
Birth Control 
If you are a woman who is breast feeding or pregnant, you may not take part in the study because 
we don’t know how this medicine would affect your baby or your unborn child. If you are a 
woman who can become pregnant, or are the partner of a woman who can become pregnant, you 
will need to practice an effective form of birth control before starting study treatment, during 
study treatment, and for 3 months after you finish study treatment.  In addition, male subjects 
should not donate sperm during the study and for 3 months after the last dose of study therapy. If 
you think that you or your partner is pregnant, you should tell your study doctor or nurse at once.   
Effective forms of birth control include:  
x abstinence  
x intrauterine device (IUD) 
x hormonal [birth control pills, injections, or implants] 
x tubal ligation 
x vasectomy 
Risks or Discomforts of Participation 
Risks and Possible Undesirable Effects of LMB-100 
Because LMB-100 is still being tested for safety, we do not know all of the possible side effects.  
However, below is a list of the most common and most serious side effects occurring on an 
earlier and ongoing studies, some occurring at higher doses than will be used in this study. 
The most common side effects (some were serious) were: 
x Low levels of the blood protein albumin which may lead to swelling, muscle weakness or 
loss of appetite 
x Tiredness 
x Swelling of the arms and legs 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 6 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
x Nausea 
x Fever 
x Decreased appetite 
x Shortness of breath 
x Pain in muscles  
x Reactions during or following the infusion of the drug which may cause fever, chills, rash 
or low blood pressure 
Less common, but serious side effects included: 
x Fluid in the organs which may cause low blood pressure, shortness of breath, swelling of 
ankles 
x Abnormal heartbeat 
x Pain in joints 
x Kidney damage which may cause swelling, may require dialysis 
Other possible side effects 
Other possible side effects discussed below are based on side effects that occurred when testing a 
similar agent, SS1P and also in animal studies of LMB-100.  It is possible that there may be 
other unexpected side-effects that occur in addition to those listed below. 
LMB-100 may cause inflammation to membranes causing chest pain, shortness of breath, low 
blood pressure, and heart failure.  In animals, some mild kidney toxicity was seen, characterized 
by increased enzymes and protein in the urine. This will be checked for with regular blood and 
urine tests. 
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. 
There may also be pain and swelling at the infusion site. 
It is important that you contact your doctor as soon as you experience any side effects whether 
you think the treatment has caused them or not.  You must also tell your doctor if you have 
started any new medication or had a change to your existing medication.  This includes 
medications available without a prescription (over the counter) and alternative medicines.  If you 
have any questions or concerns about any of the information provided above, about the possible 
side effects of treatment, or the possible consequences of treatment for those side effects, please 
ask the principal investigator or the research staff for more information.  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 7 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
The most important symptoms you need to report to your doctor immediately are: 
o possible infusion or allergic reactions (symptoms that start during or within a few 
hours of the infusion, e.g. wheezing, tightness in the throat or chest, rash, and 
facial swelling) 
o chest pain 
o shortness of breath 
o palpitations (fast heart beat) 
o bleeding and high fever 
o impaired brain function (e.g., dizziness, blurred vision, confusion) 
 
 
 
If you experience any severe or dangerous side effect, you should: 
1. Seek professional medical help immediately. 
2. Call your study doctor. 
3. If necessary, go to the nearest emergency room. 
 
Risks of nab-paclitaxel 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving nab-paclitaxel, more than 20 and up to 100 may have: 
x Anemia which may cause tiredness, or may require blood transfusions 
x Infection, especially when white blood cell count is low 
x Diarrhea, nausea, vomiting 
x Sores in mouth which may cause difficulty swallowing 
x Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, 
swelling of the face or throat 
x Bruising, bleeding 
x Pain 
x Muscle weakness 
x Numbness, tingling or pain of the arms and legs 
x Hair loss 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving nab-paclitaxel, from 4 to 20 may have: 
x Abnormal heartbeat 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 8 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving nab-paclitaxel, from 4 to 20 may have: 
x Damage to the lungs which may cause shortness of breath 
x Blood clot which may cause swelling, pain, shortness of breath 
 
RARE, AND SERIOUS 
In 100 people receiving nab-paclitaxel, 3 or fewer may have: 
x Heart attack or heart failure which may cause shortness of breath, swelling of ankles, and 
tiredness 
x A tear or a hole in the stomach which may cause belly pain or that may require surgery 
 
Nab-paclitaxel may cause serious birth defects. Please refer to the section about birth control for 
more information on how to protect yourself if you are a female who is able to get pregnant or a 
male patient who has a partner who is able to get pregnant. Nab-paclitaxel can cause irreversible 
infertility in male patients. Male patients should seek advice on conservation of sperm prior to 
treatment. 
Risks from pre-medications 
Acetaminophen  
Acetaminophen is considered to be safe and effective in the recommended doses. However, 
when taken incorrectly acetaminophen can cause liver damage. Your risk of liver damage may 
be increased if you drink more than three alcoholic drinks every day, take more than the 
recommended dose (overdose), or if you take any additional drugs that also contain 
acetaminophen at the same time. 
Diphenhydramine 
Drowsiness, dizziness, constipation, stomach upset, blurred vision, or dry mouth/nose/throat may 
occur when taking diphenhydramine.Ranitidine:   
It can cause constipation, diarrhea, headache, nausea or upset stomach.  Rare serious side effects 
include severe allergic reaction with rash, hives, itching, difficulty breathing; confusion, dark 
urine, depression, fast or slow heartbeat, unusual bruising or bleeding, yellowing of the eyes or 
skin (indicating liver damage). 
Dexamethasone:   
Stomach upset, headache, dizziness, changes in your period, trouble sleeping, increased appetite, 
or weight gain may occur. Rarely patients using dexamethasone have experienced increased 
infection, bone/joint pain, thirst, increased urination, irregular heartbeat, eye pain, vision 
problems, black stools, vomit that looks like coffee grounds, puffy face, swelling of the feet and 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 9 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
ankles, pain/redness/swelling of the arms or legs, tiredness, mood changes, unusual hair/skin 
growth, muscle cramps, weakness, easy bruising/bleeding, slow wound healing, thinning skin 
and seizures. 
Risks from Study Procedures 
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.  
ECGs 
The glue used to keep the electrodes in place during the ECG may irritate your skin and caused 
redness.  
Central Line Insertion 
x Contamination of the catheter which would result in a serious blood stream infection, 
requiring admission to the hospital and giving you antibiotics through the vein. 
x Collapsed lung particularly if the central line is placed in the vein under your collarbone. 
Collapsed lung is treated with a chest tube when necessary. 
x During the insertion of some types of central lines, the heart may be irritated by the 
process while the line travels through the blood vessels near the heart, causing an 
alteration in the heart's rhythm. This typically gets better once the line is in place but may 
require medication for some rare individuals. 
x Air embolism, a condition where air enters the blood stream and begins to travel through 
the body. This condition, which is very serious, is also very rare and largely preventable. 
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, infection or of an allergic reaction to 
the anesthetic agent used to anesthetize the skin at the biopsy site.  Once the sample has been 
obtained, a stitch may be used to close the wound and assist in healing.  
In some cases, we may use CT scans to help guide us during your tumor biopsy.  This introduces 
the added risk of research radiation.  This research study may involve exposure to radiation from 
up to 1 CT guided research biopsy.  This radiation exposure is not required for your medical care 
and is for research purposes only. The amount of radiation you will receive in this study is 0.77 
rem which is below the guideline of 5 rem per year allowed for research subjects by the NIH 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 10 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Radiation Safety Committee.  The average person in the United States receives a radiation 
exposure of 0.3 rem per year from natural sources, such as the sun, outer space, and the earth's 
air and soil.  If you would like more information about radiation, please ask the investigator for a 
copy of the pamphlet, An Introduction to Radiation for NIH Research Subjects. 
While there is no direct evidence that the amount of exposure received from participating in 
this study is harmful, there is indirect evidence it may not be completely safe.  There may 
be a very slight increase in the risk of cancer.  
Please tell your doctor if you have had any radiation exposure in the past year, either from 
other research studies or from medical tests or care, so we can make sure that you will not 
receive too much radiation. Radiation exposure includes x-rays taken in radiology 
departments, cardiac catheterization, and fluoroscopy as well as nuclear medicine scans in 
which radioactive materials were injected into your body.  
Potential Benefits of Participation 
Are there benefits to taking part in this study?  
The aim of this study is to find a safe dose as well as to see if this experimental treatment will 
cause your tumors to shrink.  We do not know if you will receive personal, medical benefit from 
taking part in this study.  These potential benefits could include shrinking of your tumor or 
lessening of 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, although the knowledge gained from this study may help others in 
the future who have cancer.   
What other choices do I have if I do not take part in this study?  
Instead of being in this study, you have these options: 
x Getting treatment or care for your cancer without being in a study, including standard 
options such as nanoliposomal irinotecan (Onivyde) 
x Taking part in another study 
x Getting comfort care, also called palliative care.  This type of care helps reduce pain, 
tiredness, appetite problems and other problems caused by the cancer.  It does not treat 
the cancer directly.  Instead, it tries to improve how you feel.  Comfort care tries to keep 
you as active and comfortable as possible. 
Please talk to your doctor about these and other options. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 11 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Research Subject’s Rights 
What are the costs of taking part in this study?  
If you choose to take part in the study, the following will apply, in keeping with the NIH policy: 
x 
You will receive study treatment at no charge to you. This may include 
surgery, medicines, laboratory testing, x-rays or scans done at the 
Clinical Center, National Institutes of Health (NIH), or arranged for you 
by the research team to be done outside the Clinical Center, NIH if the 
study related treatment is not available at the NIH.  
x 
There are limited funds available to cover the cost of some tests and 
procedures performed outside the Clinical Center, NIH.  You may have 
to pay for these costs if they are not covered by your insurance company. 
x 
Medicines that are not part of the study treatment will not be provided or 
paid for by the Clinical Center, NIH. 
x 
Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
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: 
x The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), which are involved in keeping research safe for people. 
x NIH Intramural Institutional Review Board 
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.  
Certificate of Confidentiality  
To help us protect your privacy, we have obtained a Certificate of Confidentiality. The 
researchers can use this Certificate to legally refuse to disclose information that may identify you 
in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for 
example, if there is a court subpoena. The researchers will use the Certificate to resist any 
demands for information that would identify you, except as explained below. 
You should also know that there are several circumstances in which the Certificate does not 
provide coverage. These include when information:  
x will be used for auditing or program evaluation internally by the NIH; or  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 12 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
x must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA).  
x is necessary for your medical treatment and you have consented to this disclosure;  
x is for other research.  
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible 
as evidence or used for any purpose in any action, suit, or proceeding without your consent.  
You should understand that a Certificate of Confidentiality does not prevent you or a member of 
your family from voluntarily releasing information about yourself or your involvement in this 
research. If an insurer, employer, or other person obtains your written consent to receive research 
information, then the researchers will not use the Certificate to withhold that information. 
The Certificate of Confidentiality will not protect against the required reporting by hospital staff 
of information on suspected child abuse, reportable communicable diseases, and/or possible 
threat of harm to self or others. 
Stopping Therapy  
Your doctor may decide to stop your therapy for the following reasons: 
x if he/she believes that it is in your best interest 
x if your disease comes back during treatment 
x if you become pregnant 
x if you have side effects from the treatment that your doctor thinks are too severe 
x if new information shows that another treatment would be better for you 
In this case, you will be informed of the reason therapy is being stopped. 
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. However, according to FDA guidelines, 
information collected on you up to that point may still be provided to collaborators or designated 
representatives. If you withdraw your consent and leave the trial, any samples of yours that have 
been obtained for the study and stored at the NCI can be destroyed upon request. However, any 
samples and data generated from the samples that have already been distributed to other 
researchers or placed in the research databases cannot be recalled and destroyed. 
Conflict of Interest 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a Protocol Review Guide.  You may ask your research 
team for a copy of the Protocol Review Guide or for more information.  Members of the research 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 13 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study.  This is allowed under federal rules and is not a 
conflict of interest.  
The National Institutes of Health and the research team for this study have developed a drug 
being used in this study.  This means it is possible that the results of this study could lead to 
payments to NIH scientists and to the NIH. By law, government scientists are required to receive 
such payments for their inventions. You will not receive any money from the development of 
LMB-100 in combination with nab-paclitaxel.  
Use of Specimens and Data for Future Research 
To advance science, it is helpful for researchers to share information they get from studying 
human samples.  They do this by putting it into one or more scientific databases, where it is 
stored along with information from other studies. A researcher who wants to study the 
information must apply to the database and be approved.  Researchers use specimens and data 
stored in scientific databases to advance science and learn about health and disease.   
We plan to keep some of your specimens and data that we collect and use them for future 
research and share them with other researchers. We will not contact you to ask about each of 
these future uses.  These specimens and data will be stripped of identifiers such as name, address 
or account number, so that it may be used for future research on any topic and shared broadly for 
research purposes. Your specimens and data will be used for research purposes only and will not 
benefit you.  It is also possible that the stored specimens and data may never be used.  Results of 
research done on your specimens and data will not be available to you or your doctor.  It might 
help people who have cancer and other diseases in the future.   
If do not want your stored specimens and data used for future research, please contact us in 
writing and let us know that you do not want us to use your specimens and/or data.  Then any 
specimens that have not already been used or shared will be destroyed and your data will not be 
used for future research. However, it may not be possible to withdraw or delete materials or data 
once they have been shared with other researchers. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 16-C-0128 
CONTINUATION: page 14 of 15 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
OTHER PERTINENT INFORMATION 
1. 
Confidentiality.  When results of an NIH research study are reported in medical journals 
or at scientific meetings, the people who take part are not named and identified.  In most cases, 
the NIH will not release any information about your research involvement without your written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance 
company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration (FDA), 
members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
2. 
Policy Regarding Research-Related Injuries.  The 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 National Institutes of Health, the Clinical Center, or the Federal Government.  
However, you have the right to pursue legal remedy if you believe that your injury justifies such 
action. 
3. 
Payments.  The amount of payment to research volunteers is guided by the National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies at 
the National Institutes of Health.  Reimbursement of travel and subsistence will be offered 
consistent with NIH guidelines. 
4. 
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, Christine Alewine, M.D., Ph.D., Building 37, Room 5116, Telephone:  
240-760-6146. You may also call the Clinical Center Patient Representative at 301-496-2626. If 
you have any questions about the use of your specimens or data for future research studies, you 
may also contact the Office of the Clinical Director, Telephone:  240-760-6070. 
5. 
Consent Document.  Please keep a copy of this document in case you want to read it 
again. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 16-C-0128 
CONTINUATION: page 15 of 15 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
 
 
 
Signature of Adult Patient/ 
Legal Representative 
Date 
 
 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to 
participate in the study. 
 
  
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM AUGUST 31, 2020 THROUGH AUGUST 30, 2021.  
 
 
 
 
 
 
 
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name 
 

ICF_002.pdf: 
\MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
16-C-0128 
PRINCIPAL INVESTIGATOR: 
Christine Alewine, M.D., Ph.D. 
STUDY TITLE:  
A Phase I/II Study of Mesothelin-Targeted Immunotoxin LMB-100 Alone or in 
Combination with Nab-Paclitaxel in Participants with Previously Treated Metastatic and/ 
or Locally Advanced Pancreatic Ductal Adenocarcinoma and Mesothelin Expressing 
Solid Tumors 
 
Continuing Review Approved by the IRB on 08/31/20 
Amendment Approved by the IRB on 12/13/18 (L) 
 
Date posted to web: 09/04/20   
Arm A1 (Phase 1 Short Infusion) 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent (1) 
 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary.  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
You may receive no benefit from taking part.  The research may give us knowledge that 
may help people in the future. 
Second, 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).  If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
Now we will describe this research study.  Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional.   
Why is this study being done?  
LMB-100 is an investigational agent, meaning that it has not been approved by the US Food and 
Drug Administration. It is a type of manufactured protein which is similar to protein normally 
produced by your body.  LMB-100 is attracted to the mesothelin protein, which is present on the 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 2 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
surface of many different tumors, including many, but not all, pancreatic cancers. The 
mesothelin protein is found in only a very small number of normal tissues.  After binding to the 
mesothelin on tumors, LMB-100 can then attack and kill cancer cells.  
Nab-paclitaxel is an FDA approved agent in the treatment of pancreatic cancer. It has not, 
however been tried in combination with LMB-100. 
This study, which is divided into multiple parts will determine a safe dose of LMB-100 on 
different administration schedules alone or in combination with a fixed dose of nab-paclitaxel in 
the phase 1 portion. 
x In phase 1, Arm A1 – subjects with pancreatic cancer will receive nab-paclitaxel in 
combination with LMB-100 given every other day for 3 days in each 21-day cycle. 
x In phase 1, Arm B1, (single Agent lead-in) – subjects that have tumors that test positive 
for mesothelin will receive LMB-100 alone for 1 or 2 days continuously or two 24-hour 
infusions (days 1 and 4) depending on dose level in each 21-day cycle. 
x In phase 1, Arm B2, (combination therapy) – subjects with pancreatic cancer will receive 
nab-paclitaxel in combination with LMB-100 given for 24 hours continuously on day 1 
of each 14-day cycle.  
In the phase 2 portion of the study (Arm A2), we will determine whether the dose established in 
phase 1, Arm A1 reduces the size of tumors in patients with pancreatic cancer.  
You are participating in the phase 1, Arm A1 portion of the study. 
Why are you being asked to take part in this study? 
You are being asked to take part in this study because you have advanced pancreatic cancer that 
has worsened after anti-cancer therapy.  
How many people will take part in this study?  
Up to 100 participants will be enrolled in the study overall. 
Description of Research Study 
Participants will be enrolled in the phase 1 portion of the study in groups of 3 to 6 at increasing 
doses until a dose is reach where 2 or more participants experience intolerable side effects.  If no 
dose is reached where 2 or more participants experience intolerable side effects, then the highest 
tested dose will be selected as the maximum tolerated dose (MTD).  If a dose is reached where 
there are 2 or more intolerable side effects, the dose just below it will be selected as the MTD 
provided that no more than 1 of 6 participants experienced intolerable side effects at that dose.   


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 3 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
You will receive LMB-100 through an IV catheter (a tube inserted in a vein, usually in your arm 
though, as stated below in During the Study, it may be placed in a different location if your 
doctor feels it is necessary) on day 1, day 3 and day 5 of each 21-day cycle.  Nab-paclitaxel will 
also be given by IV on days 1 and 8 of each 21-day cycle. You will receive LMB-100 in 
combination with nab-paclitaxel for up to 2 cycles or until your disease worsens or you have 
intolerable side effects, whichever happens first. We will continue to follow you after you have 
finished taking the study drug to keep track of your disease status (progression), your survival 
status or whether you have taken any additional cancer therapy.  The specific procedures you 
will have are described below. 
What will happen if you take part in this research 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 
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 are performed under a separate consent, include: 
x Confirmation of diagnosis (You must provide a sample tumor tissue for formal evaluation 
by the NCI Laboratory of Pathology.  The tissue may be from a previous surgery or 
biopsy.  If none is available, we will ask you to have a biopsy to provide a fresh sample).   
x Medical history and physical examination 
x Routine blood and urine tests including pregnancy test in women who can have children.  
Pregnant women will not be allowed on study. 
x Scans  
x Electrocardiogram (ECG) 
x Echocardiogram 
x Tests for viruses (hepatitis and HIV) 
x Blood for tumor markers 
During the study 
Once it is determined that you are eligible and you have signed the consent for the study, you 
will receive IV infusions of LMB-100 and nab-paclitaxel as described above. Each LMB-100 
infusion will last for as long as 3 hours.  Each nab-paclitaxel infusion lasts about 30 minutes. If 
your doctor feels that it is necessary, you may receive the study drugs through a central line (an 
IV tube placed in a large vein for long term therapy) or through a mediport if you already have 
one installed.  On day 1 of each cycle, when both medications are given, you will receive the 
LMB-100 about 30 minutes after you have completed the nab-paclitaxel infusion.  You will be 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 4 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
monitored for side effects for 2 hours after the first LMB-100 infusion, and for 30 minutes after 
all other LMB-100 infusions if no side effects occurred previously.  You will be given standard 
pre-medications that include an antihistamine (such a Benadryl), acetaminophen (Tylenol) and 
ranitidine to help prevent infusion related side effects. Dexamethasone or an equivalent steroid 
may be added if you experience a reaction even after using the standard pre-medications. 
While you are taking study medication, we will perform a number of tests and examinations for 
safety and to test the effect of the study therapy: 
These include routine blood and urine tests that will be on each day you receive an infusion, 
scans that will be performed approximately every 6 weeks, and ECGs that will be done on day 1 
of each cycle. 
In addition to the safety tests, we will also perform tests for research studies to find out how your 
body handles the drugs (PKs), how your body, including your immune system, reacts to the drug 
and how certain side effects of the LMB-100 might be caused. We will also conduct genetic 
studies focused on genes that process drugs, nab-paclitaxel in particular.  Most of the sampling 
for these research tests will be done before your first dose of study drug or on the days you take 
the study drug (just before or just after you get the study drug). In cycle 1, we will also collect 
samples on day 6 (may sometimes be done on day 5). In addition, on day 1 of cycle 1 samples 
will be drawn before your infusion and periodically for up to 72 hours (3 days) after the end of 
your nab-paclitaxel infusion. 
When you are finished taking the drugs 
Withdrawal Visit 
If you received 2 cycles of LMB-100, the following assessments will be performed at the end of 
cycle 2: 
x Medical history and physical examination 
x Routine blood and urine tests 
x Scans 
x Blood tests for tumor markers 
x ECG 
Safety Visit 
If you did not complete both cycles of the study drug, or if you have completed 2 cycles but the 
scans above showed that your disease has gotten worse, you will be asked to return to the NIH 
approximately 3 – 6 weeks after you have had last dose of study drug for a safety visit.  
If you completed cycle 2 and your scans did not reveal worsening disease, you will be asked to 
return approximately six weeks after your last scan for a restaging scan and safety visit. 
The visit will include the following tests: 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 5 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
x Medical history and physical exam 
x Routine blood and urine tests including pregnancy test in women who can have children 
x ECG 
x Scans if your disease has not worsened since the beginning of the study 
Long term follow up 
If after the safety visit, your disease remains stable or improved, you will continue to be scanned 
every 6 weeks until your disease gets worse. 
About once a year, regardless of whether your disease has gotten worse, we will contact you or 
your physician by telephone to ask about any other cancer therapies you may have started and 
about your survival status. 
Birth Control 
If you are a woman who is breast feeding or pregnant, you may not take part in the study because 
we don’t know how this medicine would affect your baby or your unborn child. If you are a 
woman who can become pregnant, or are the partner of a woman who can become pregnant, you 
will need to practice an effective form of birth control before starting study treatment, during 
study treatment, and for 3 months after you finish study treatment.  In addition, male subjects 
should not donate sperm during the study and for 3 months after the last dose of study therapy. If 
you think that you or your partner is pregnant, you should tell your study doctor or nurse at once.   
Effective forms of birth control include:  
x abstinence  
x intrauterine device (IUD) 
x hormonal [birth control pills, injections, or implants] 
x tubal ligation 
x vasectomy 
Risks or Discomforts of Participation 
Risks and Possible Undesirable Effects of LMB-100 
Because LMB-100 is still being tested for safety, we do not know all of the possible side effects.  
However, below is a list of the most common and most serious side effects occurring on an 
earlier and ongoing studies, some occurring at higher doses than will be used in this study. 
The most common side effects (some were serious) were: 
x Low levels of the blood protein albumin which may lead to swelling, muscle weakness or 
loss of appetite 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 6 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
x Tiredness 
x Swelling of the arms and legs 
x Nausea 
x Fever 
x Decreased appetite 
x Shortness of breath 
x Pain in muscles  
x Reactions during or following the infusion of the drug which may cause fever, chills, rash 
or low blood pressure 
Less common, but serious side effects included: 
x Fluid in the organs which may cause low blood pressure, shortness of breath, swelling of 
ankles 
x Abnormal heartbeat 
x Pain in joints 
x Kidney damage which may cause swelling, may require dialysis 
Other possible side effects 
Other possible side effects discussed below are based on side effects that occurred when testing a 
similar agent, SS1P and also in animal studies of LMB-100.  It is possible that there may be 
other unexpected side-effects that occur in addition to those listed below. 
LMB-100 may cause inflammation to membranes causing chest pain, shortness of breath, low 
blood pressure, and heart failure.  In animals, some mild kidney toxicity was seen, characterized 
by increased enzymes and protein in the urine. This will be checked for with regular blood and 
urine tests. 
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. 
There may also be pain and swelling at the infusion site. 
It is important that you contact your doctor as soon as you experience any side effects whether 
you think the treatment has caused them or not.  You must also tell your doctor if you have 
started any new medication or had a change to your existing medication.  This includes 
medications available without a prescription (over the counter) and alternative medicines.  If you 
have any questions or concerns about any of the information provided above, about the possible 
side effects of treatment, or the possible consequences of treatment for those side effects, please 
ask the principal investigator or the research staff for more information.  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 7 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
The most important symptoms you need to report to your doctor immediately are: 
o possible infusion or allergic reactions (symptoms that start during or within a few 
hours of the infusion, e.g. wheezing, tightness in the throat or chest, rash, and 
facial swelling) 
o chest pain 
o shortness of breath 
o palpitations (fast heart beat) 
o bleeding and high fever 
o impaired brain function (e.g., dizziness, blurred vision, confusion) 
 
 
 
If you experience any severe or dangerous side effect, you should: 
1. Seek professional medical help immediately. 
2. Call your study doctor. 
3. If necessary, go to the nearest emergency room. 
 
Risks of nab-paclitaxel 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving nab-paclitaxel, more than 20 and up to 100 may have: 
x Anemia which may cause tiredness, or may require blood transfusions 
x Infection, especially when white blood cell count is low 
x Diarrhea, nausea, vomiting 
x Sores in mouth which may cause difficulty swallowing 
x Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, 
swelling of the face or throat 
x Bruising, bleeding 
x Pain 
x Muscle weakness 
x Numbness, tingling or pain of the arms and legs 
x Hair loss 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving nab-paclitaxel, from 4 to 20 may have: 
x Abnormal heartbeat 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 8 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving nab-paclitaxel, from 4 to 20 may have: 
x Damage to the lungs which may cause shortness of breath 
x Blood clot which may cause swelling, pain, shortness of breath 
 
RARE, AND SERIOUS 
In 100 people receiving nab-paclitaxel, 3 or fewer may have: 
x Heart attack or heart failure which may cause shortness of breath, swelling of ankles, and 
tiredness 
x A tear or a hole in the stomach which may cause belly pain or that may require surgery 
 
Nab-paclitaxel may cause serious birth defects. Please refer to the section about birth control for 
more information on how to protect yourself if you are a female who is able to get pregnant or a 
male patient who has a partner who is able to get pregnant. Nab-paclitaxel can cause irreversible 
infertility in male patients. Male patients should seek advice on conservation of sperm prior to 
treatment. 
Risks from pre-medications 
Acetaminophen  
Acetaminophen is considered to be safe and effective in the recommended doses. However, 
when taken incorrectly acetaminophen can cause liver damage. Your risk of liver damage may 
be increased if you drink more than three alcoholic drinks every day, take more than the 
recommended dose (overdose), or if you take any additional drugs that also contain 
acetaminophen at the same time. 
Diphenhydramine 
Drowsiness, dizziness, constipation, stomach upset, blurred vision, or dry mouth/nose/throat may 
occur when taking diphenhydramine.Ranitidine:   
It can cause constipation, diarrhea, headache, nausea or upset stomach.  Rare serious side effects 
include severe allergic reaction with rash, hives, itching, difficulty breathing; confusion, dark 
urine, depression, fast or slow heartbeat, unusual bruising or bleeding, yellowing of the eyes or 
skin (indicating liver damage). 
Dexamethasone:   
Stomach upset, headache, dizziness, changes in your period, trouble sleeping, increased appetite, 
or weight gain may occur. Rarely patients using dexamethasone have experienced increased 
infection, bone/joint pain, thirst, increased urination, irregular heartbeat, eye pain, vision 
problems, black stools, vomit that looks like coffee grounds, puffy face, swelling of the feet and 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 9 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
ankles, pain/redness/swelling of the arms or legs, tiredness, mood changes, unusual hair/skin 
growth, muscle cramps, weakness, easy bruising/bleeding, slow wound healing, thinning skin 
and seizures. 
Risks from Study Procedures 
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.  
ECGs 
The glue used to keep the electrodes in place during the ECG may irritate your skin and caused 
redness.  
Central Line Insertion 
x Contamination of the catheter which would result in a serious blood stream infection, 
requiring admission to the hospital and giving you antibiotics through the vein. 
x Collapsed lung particularly if the central line is placed in the vein under your collarbone. 
Collapsed lung is treated with a chest tube when necessary. 
x During the insertion of some types of central lines, the heart may be irritated by the 
process while the line travels through the blood vessels near the heart, causing an 
alteration in the heart's rhythm. This typically gets better once the line is in place but may 
require medication for some rare individuals. 
x Air embolism, a condition where air enters the blood stream and begins to travel through 
the body. This condition, which is very serious, is also very rare and largely preventable. 
Potential Benefits of Participation 
Are there benefits to taking part in this study?  
The aim of this study is to find a safe dose as well as to see if this experimental treatment will 
cause your tumors to shrink.  We do not know if you will receive personal, medical benefit from 
taking part in this study.  These potential benefits could include shrinking of your tumor or 
lessening of 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, although the knowledge gained from this study may help others in 
the future who have cancer.   


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 10 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
What other choices do I have if I do not take part in this study?  
Instead of being in this study, you have these options: 
x Getting treatment or care for your cancer without being in a study, including standard 
options such as nanoliposomal irinotecan (Onivyde) 
x Taking part in another study 
x Getting comfort care, also called palliative care.  This type of care helps reduce pain, 
tiredness, appetite problems and other problems caused by the cancer.  It does not treat 
the cancer directly.  Instead, it tries to improve how you feel.  Comfort care tries to keep 
you as active and comfortable as possible. 
Please talk to your doctor about these and other options. 
Research Subject’s Rights 
What are the costs of taking part in this study?  
If you choose to take part in the study, the following will apply, in keeping with the NIH policy: 
x 
You will receive study treatment at no charge to you. This may include 
surgery, medicines, laboratory testing, x-rays or scans done at the 
Clinical Center, National Institutes of Health (NIH), or arranged for you 
by the research team to be done outside the Clinical Center, NIH if the 
study related treatment is not available at the NIH.  
x 
There are limited funds available to cover the cost of some tests and 
procedures performed outside the Clinical Center, NIH.  You may have 
to pay for these costs if they are not covered by your insurance company. 
x 
Medicines that are not part of the study treatment will not be provided or 
paid for by the Clinical Center, NIH. 
x 
Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
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: 
x The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), which are involved in keeping research safe for people. 
x NIH Intramural Institutional Review Board 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 11 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
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.  
Certificate of Confidentiality  
To help us protect your privacy, we have obtained a Certificate of Confidentiality. The 
researchers can use this Certificate to legally refuse to disclose information that may identify you 
in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for 
example, if there is a court subpoena. The researchers will use the Certificate to resist any 
demands for information that would identify you, except as explained below. 
You should also know that there are several circumstances in which the Certificate does not 
provide coverage. These include when information:  
x will be used for auditing or program evaluation internally by the NIH; or  
x must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA).  
x is necessary for your medical treatment and you have consented to this disclosure;  
x is for other research.  
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible 
as evidence or used for any purpose in any action, suit, or proceeding without your consent.  
You should understand that a Certificate of Confidentiality does not prevent you or a member of 
your family from voluntarily releasing information about yourself or your involvement in this 
research. If an insurer, employer, or other person obtains your written consent to receive research 
information, then the researchers will not use the Certificate to withhold that information. 
The Certificate of Confidentiality will not protect against the required reporting by hospital staff 
of information on suspected child abuse, reportable communicable diseases, and/or possible 
threat of harm to self or others. 
Stopping Therapy  
Your doctor may decide to stop your therapy for the following reasons: 
x if he/she believes that it is in your best interest 
x if your disease comes back during treatment 
x if you become pregnant 
x if you have side effects from the treatment that your doctor thinks are too severe 
x if new information shows that another treatment would be better for you 
In this case, you will be informed of the reason therapy is being stopped. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 12 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
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. However, according to FDA guidelines, 
information collected on you up to that point may still be provided to collaborators or designated 
representatives. If you withdraw your consent and leave the trial, any samples of yours that have 
been obtained for the study and stored at the NCI can be destroyed upon request. However, any 
samples and data generated from the samples that have already been distributed to other 
researchers or placed in the research databases cannot be recalled and destroyed. 
Conflict of Interest 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a Protocol Review Guide.  You may ask your research 
team for a copy of the Protocol Review Guide or for more information.  Members of the research 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study.  This is allowed under federal rules and is not a 
conflict of interest.  
The National Institutes of Health and the research team for this study have developed a drug 
being used in this study.  This means it is possible that the results of this study could lead to 
payments to NIH scientists and to the NIH. By law, government scientists are required to receive 
such payments for their inventions. You will not receive any money from the development of 
LMB-100 in combination with nab-paclitaxel.  
Use of Specimens and Data for Future Research 
To advance science, it is helpful for researchers to share information they get from studying 
human samples.  They do this by putting it into one or more scientific databases, where it is 
stored along with information from other studies. A researcher who wants to study the 
information must apply to the database and be approved.  Researchers use specimens and data 
stored in scientific databases to advance science and learn about health and disease.   
We plan to keep some of your specimens and data that we collect and use them for future 
research and share them with other researchers. We will not contact you to ask about each of 
these future uses.  These specimens and data will be stripped of identifiers such as name, address 
or account number, so that it may be used for future research on any topic and shared broadly for 
research purposes. Your specimens and data will be used for research purposes only and will not 
benefit you.  It is also possible that the stored specimens and data may never be used.  Results of 
research done on your specimens and data will not be available to you or your doctor.  It might 
help people who have cancer and other diseases in the future.   


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 13 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
If do not want your stored specimens and data used for future research, please contact us in 
writing and let us know that you do not want us to use your specimens and/or data.  Then any 
specimens that have not already been used or shared will be destroyed and your data will not be 
used for future research. However, it may not be possible to withdraw or delete materials or data 
once they have been shared with other researchers. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 16-C-0128 
CONTINUATION: page 14 of 15 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
OTHER PERTINENT INFORMATION 
1. 
Confidentiality.  When results of an NIH research study are reported in medical journals 
or at scientific meetings, the people who take part are not named and identified.  In most cases, 
the NIH will not release any information about your research involvement without your written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance 
company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration (FDA), 
members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
2. 
Policy Regarding Research-Related Injuries.  The 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 National Institutes of Health, the Clinical Center, or the Federal Government.  
However, you have the right to pursue legal remedy if you believe that your injury justifies such 
action. 
3. 
Payments.  The amount of payment to research volunteers is guided by the National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies at 
the National Institutes of Health.  Reimbursement of travel and subsistence will be offered 
consistent with NIH guidelines. 
4. 
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, Christine Alewine, M.D., Ph.D., Building 37, Room 5116, Telephone:  
240-760-6146. You may also call the Clinical Center Patient Representative at 301-496-2626. If 
you have any questions about the use of your specimens or data for future research studies, you 
may also contact the Office of the Clinical Director, Telephone:  240-760-6070. 
5. 
Consent Document.  Please keep a copy of this document in case you want to read it 
again. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 16-C-0128 
CONTINUATION: page 15 of 15 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
 
 
 
Signature of Adult Patient/ 
Legal Representative 
Date 
 
 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to 
participate in the study. 
 
  
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM AUGUST 31, 2020 THROUGH AUGUST 30, 2021.  
 
 
 
 
 
 
 
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name 
 

Prot_SAP_000.pdf: 
Abbreviated Title: LMB-100 + Abrx in PDA 
Version Date: 12/11/2018 
 
1 
 
Abbreviated Title: LMB-100 + Abrx in PDA 
CC Protocol #: 16C0128 L 
Version Date: December 11, 2018 
NCT #: NCT02810418 
 
Title: A Phase I/II Study of Mesothelin-Targeted Immunotoxin LMB-100 Alone or in 
Combination with Nab-Paclitaxel in Participants with Previously Treated Metastatic and/ or 
Locally Advanced Pancreatic Ductal Adenocarcinoma and Mesothelin Expressing Solid Tumors  
NCI Principal Investigator: 
Christine Alewine, M.D., Ph.D. 
Laboratory of Molecular Biology (LMB), CCR, NCI 
Building 37, Room 5116 
9000 Rockville Pike 
Phone: 240-760-6146 
Email: Christine.alewine@nih.gov 
 
Investigational Agents:     
Drug Name: 
LMB-100 (formerly RO6927005) 
Mesothelin Expression Testing 
IND Number: 
123332 
NSR device 
Sponsor/Holder: 
Center for Cancer Research, NCI, 
NIH 
Center for Cancer Research 
Manufacturer: 
F. Hoffman-La Roche Ltd 
NCI Laboratory of Pathology 
 
Commercial Agents 
NAB Paclitaxel will be obtained from commercial sources by the NIH CC pharmacy.  


Abbreviated Title: LMB-100 + Abrx in PDA 
Version Date: 12/11/2018 
 
2 
 
PRÉCIS  
Background: 
x Pancreatic cancer is the fourth most common cause of cancer death in the United States, 
claiming more than 40,000 lives each year. 
x Incidence nearly equals mortality with just 6% of participants living five years beyond their 
diagnosis. Most patients are diagnosed at an advanced stage, but even patients with early 
stage disease have a long term survival of less than 20%. 
x Mesothelin is specifically a marker of adenocarcinoma in the human disease and is not 
expressed in preceding pre-malignant stages of tumor development  
x Expression of mesothelin in pancreatic ductal adenocarcinoma (PDA) has been examined 
in several published studies and ranges from 86 to 100% 
x Recombinant immunotoxins (RITs) are antibody-based therapeutics that carry a toxin 
payload.  RITs that target mesothelin contain a genetically engineered variant of 
Pseudomonas exotoxin A (PE) in which the native cell-binding domain of PE is replaced 
by the mesothelin-binding antibody fragment. SS1P was the first mesothelin-targeted RIT 
tested in patients.  
x LMB-100 contains a newly engineered PE fragment that has improved activity against most 
pancreatic cancer cell lines in vitro, and is also much less toxic than SS1P in pre-clinical 
models. The new PE contains modifications specifically designed to reduce 
immunogenicity of the molecule. 
x Pre-administration of paclitaxel with SS1P was demonstrated to increase the amount of 
immunotoxin internalized by tumor cells and to reduce levels of shed mesothelin in the 
intra-tumoral environment so that more immunotoxin could bind tumor cells. The effect is 
even more pronounced with NAB-paclitaxel in a pancreatic cancer model. 
x Initial clinical testing of LMB-100 was performed by Roche in a multi-center international 
first in human trial (NCT02317419). The agent was well tolerated and appeared to have 
decreased immunogenicity compared to SS1P based on preliminary results. 
x In initial and subsequent clinical testing, LMB-100 was found to have half-life of ~60 mins.  
This is shorter then that measured for previous RITs used in the clinical setting. 
Primary Objectives: 
¾ Arm A1 (Phase I, short infusion): 
x To determine the maximum tolerated dose of short infusion LMB-100 in combination nab-
paclitaxel chemotherapy in participants with advanced pancreatic cancer  
¾ Arm B1 (Continuous infusion single agent lead-in): 
x To determine the maximum tolerated dose of LMB-100 given in a continuous infusion 
format over 24 - 96 hours to patients with advanced solid tumors that express mesothelin 
¾ Arm B2 (Continuous infusion combination therapy): 
x Establish a tolerated dose of LMB-100 given by continuous infusion in combination with 
nab-paclitaxel chemotherapy in participants with advanced pancreatic cancer  


Abbreviated Title: LMB-100 + Abrx in PDA 
Version Date: 12/11/2018 
 
3 
 
¾ Arm A2 (Phase II, short infusion): 
x To determine the objective response rate (PR+CR) according to RECIST 1.1 criteria of short 
infusion LMB-100 in combination with nab-paclitaxel chemotherapy in participants with 
advanced pancreatic cancer 
Eligibility: 
x Age ≥ 18 years 
x Histologically confirmed recurrent, metastatic and/or advanced pancreatic ductal 
adenocarcinoma (Except for Arm B1 [Single Agent Lead-in]) 
x For Arm B1 (Single Agent Lead-in), ONLY: Histologically confirmed solid tumor 
malignancy for which no curative therapy exists with at least 25% of tumor cells expressing 
mesothelin as determined by NCI Laboratory of Pathology. Determination can be made 
using archival tumor tissue or fresh biopsy. 
x Treatment must include at least one prior chemotherapy regimen 
x No nab-paclitaxel or paclitaxel treatment in the last four months (Except for Arm B1 [Single 
Agent Lead-in]) 
x Adequate organ function 
x Participants with HIV, active HBV or HCV infections are eligible only for the Arm B1 
(Single Agent Lead-in) 
Design: 
x This study is a Phase I/II open label study to assess the safety and efficacy of LMB-100 in 
combination with the standard of care agent nab-paclitaxel in participants metastatic and/or 
locally advanced pancreatic ductal adenocarcinoma 
x Subjects will be treated for up to 2 or 3 cycles depending on arm. 
x In Arm A1 (Phase I, short infusion) of the study, up to 3 dose levels will be evaluated. LMB-
100 will be administered on days 1, 3 and 5 of a 21-day cycle and nab-paclitaxel will be 
administered on days 1 and 8 
x In Arm A2 (Phase II, short infusion), if explored, up to 20 evaluable participants (including 
those treated at 65 mcg/kg, will be enrolled. Arm A2 will not be explored if 65 mcg/kg is 
not deemed safe in Arm A1 
x In Arm B1 (Continuous infusion, single Agent Lead-in), escalating doses of single agent 
LMB-100 will be administered.  The study drug will be given as a continuous infusion for 
the 1, 2, 3, or 4 days of a 21-day cycle. 
x Arm B2 (Continuous infusion, combination therapy) will be initiated after completion of 
both Arm A1 and Arm B1 Single Agent Lead-in.  It will test a single dose level of LMB-
100 based on data from the Lead-in given in combination with nab-paclitaxel.  LMB-100 
will be given as a continuous infusion for 24 hours on Day 1 of a 14-day cycle. Nab-
paclitaxel will also be given on Day 1. 
x The Arm A2 (Phase II, short infusion) portion of the study, if explored, will be conducted 
in a Simon Minimax two stage phase II design.  The first stage will enroll 13 evaluable 
participants, including the six participants treated at 65 mcg/kg. If 1 or more has a response, 
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TABLE OF CONTENTS  
PRÉCIS ............................................................................................................................................2 
TABLE OF CONTENTS .................................................................................................................4 
1 
INTRODUCTION ..................................................................................................................9 
1.1 
Study Objectives ...............................................................................................................9 
1.1.1 
Primary Objective: ......................................................................................................9 
1.1.2 
Secondary Objectives: ................................................................................................9 
1.1.3 
Exploratory Objectives: ..............................................................................................9 
1.2 
Background and Rationale ..............................................................................................10 
1.2.1 
Background on Disease.............................................................................................10 
1.2.2 
Mesothelin (MSLN) as a therapeutic target ..............................................................10 
1.2.3 
Recombinant Immunotoxins (RITs) .........................................................................13 
1.2.4 
LMB-100...................................................................................................................15 
1.2.5 
Pharmacokinetics of LMB-100 and modeling of continuous infusion .....................24 
1.2.6 
Rationale for treating pancreatic cancer patients with LMB-100 and NAB-
paclitaxel combination ..............................................................................................25 
1.2.7 
Rationale for assessing continuous infusion of LMB-100 ........................................25 
1.2.8 
Rationale for the initial dose and schedule and subsequent dose escalation of 
continuous infusion LMB-100 ..................................................................................27 
1.2.9 
Rationale for use of mesothelin testing (NSR device) ..............................................28 
2 
ELIGIBILITY ASSESSMENT AND ENROLLMENT .......................................................29 
2.1 
Eligibility Criteria ...........................................................................................................29 
2.1.1 
Inclusion Criteria ......................................................................................................29 
2.1.2 
Exclusion Criteria .....................................................................................................31 
2.2 
Screening Evaluation ......................................................................................................31 
2.3 
Registration Procedures ..................................................................................................32 
2.3.1 
Arm B1, Single Agent Lead in Cohort Subjects with Diseases other than 
Epithelioid Mesothelioma or Pancreatic Adenocarcinoma Only ..............................32 
2.3.2 
All other subjects ......................................................................................................33 
2.3.3 
Treatment Assignment  Procedures ..........................................................................33 
3 
STUDY IMPLEMENTATION ............................................................................................34 
3.1 
Study Design ...................................................................................................................34 


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3.1.1 
Study Schema for short infusion LMB-100 with nab-paclitaxel (Arm A1 (Phase 
I))...............................................................................................................................35 
3.1.2 
Study Schema for continuous infusion LMB-100 (Arm B1 [Single Agent Lead-
in]) .............................................................................................................................36 
3.1.3 
Study Schema for continuous infusion LMB-100 with nab-paclitaxel (Arm B2) ....36 
3.1.4 
Study Schema for Phase II ........................................................................................37 
3.1.5 
Dose Limiting Toxicity .............................................................................................37 
3.1.6 
Dose Escalation .........................................................................................................38 
3.2 
Drug Administration .......................................................................................................42 
3.2.1 
LMB-100...................................................................................................................42 
3.2.2 
Nab-Paclitaxel ...........................................................................................................46 
3.2.3 
Co-administration of Nab-paclitaxel and LMB-100 .................................................46 
3.3 
Dose Modifications .........................................................................................................46 
3.3.1 
LMB-100...................................................................................................................47 
3.3.2 
Nab-paclitaxel ...........................................................................................................50 
3.4 
Study Calendars ..............................................................................................................51 
3.4.1 
Calendar for patient receiving short infusion LMB-100 (Arms A1 and A2) ...........51 
3.4.2 
Calendars subjects in Arm B1 (single agent continuous infusion LMB-100) ..........54 
3.4.3 
Calendar for Subjects in Arm B2 (LMB-100 24-hour continuous infusion 
combination therapy) ................................................................................................60 
3.5 
Criteria for Removal from Protocol Therapy and Off Study Criteria .............................63 
3.5.1 
Criteria for removal from protocol therapy ..............................................................63 
3.5.2 
Off-Study Criteria .....................................................................................................63 
4 
CONCOMITANT MEDICATIONS/MEASURES ..............................................................63 
4.1.1 
Permitted Therapy .....................................................................................................63 
4.1.2 
Prohibited Therapy....................................................................................................63 
5 
BIOSPECIMEN COLLECTION ..........................................................................................64 
5.1 
Correlative Studies for Research/Pharmacokinetic Studies ............................................64 
5.1.1 
LMB-100 Pharmacokinetic Assessments .................................................................64 
5.1.2 
Nab-Paclitaxel Pharmacokinetic Assessments .........................................................65 
5.1.3 
Pharmacogenetic Studies ..........................................................................................66 
5.1.4 
Assessment of anti-drug antibodies (ADAs) ............................................................66 
5.1.5 
Retrospective Analysis of Mesothelin Expression in tumor tissue ...........................67 


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5.1.6 
Cytokines for identification of mechanism for PE-mediated capillary leak 
syndrome ...................................................................................................................67 
5.1.7 
Circulating endothelial cells (CEP and CEC) for identification of mechanism for 
PE-mediated capillary leak syndrome ......................................................................68 
5.1.8 
Immune subset analysis ............................................................................................68 
5.1.9 
Peripheral blood immune gene expression ...............................................................69 
5.1.10 Circulating tumor cells ..............................................................................................70 
5.1.11 Treatment Effect on Tumor Microenvironment .......................................................70 
5.1.12 Serum Megakaryocyte Potentiating Factor (MPF) level ..........................................70 
5.2 
Sample Collection schedule ............................................................................................72 
5.2.1 
Sample Collection for Patients receiving short infusion LMB-100 (Arms A1 and 
A2) ............................................................................................................................72 
5.2.2 
Sample Collection for Patients receiving continuous infusion of LMB-100 (Arms 
B1 and B2) ................................................................................................................74 
5.3 
Sample Storage, Tracking and Disposition .....................................................................80 
5.3.1 
Clinical Pharmacology Program ...............................................................................80 
5.3.2 
Leidos Biomedical, Inc. Lab .....................................................................................80 
5.3.3 
Laboratory of Jane Trepel .........................................................................................81 
5.3.4 
Protocol Completion/Sample Destruction ................................................................81 
5.4 
Samples for Genetic Analysis .........................................................................................82 
6 
DATA COLLECTION AND EVALUATION .....................................................................82 
6.1 
Data Collection ...............................................................................................................82 
6.2 
Data Sharing Plans ..........................................................................................................83 
6.2.1 
Human Data Sharing Plan .........................................................................................83 
6.2.2 
Genomic Data Sharing Plan ......................................................................................83 
6.3 
Response Criteria ............................................................................................................83 
6.3.1 
Definitions.................................................................................................................84 
6.3.2 
All Diseases except pleural mesothelioma ...............................................................84 
6.3.3 
Pleural Mesothelioma ...............................................................................................89 
6.3.4 
Duration of Response ................................................................................................91 
6.3.5 
Progression-Free Survival .........................................................................................91 
6.3.6 
Objective Response Rate ..........................................................................................91 
6.3.7 
Disease Control Rate.................................................................................................91 


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6.4 
Toxicity Criteria ..............................................................................................................91 
7 
SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING 
PLAN ....................................................................................................................................91 
7.1 
Definitions.......................................................................................................................91 
7.1.1 
Adverse Event ...........................................................................................................91 
7.1.2 
Suspected adverse reaction .......................................................................................92 
7.1.3 
Unexpected adverse reaction ....................................................................................92 
7.1.4 
Serious.......................................................................................................................92 
7.1.5 
Serious Adverse Event ..............................................................................................92 
7.1.6 
Disability ...................................................................................................................92 
7.1.7 
Life-threatening adverse drug experience .................................................................92 
7.1.8 
Protocol Deviation (NIH Definition) ........................................................................93 
7.1.9 
Non-compliance (NIH Definition) ............................................................................93 
7.1.10 Unanticipated Problem..............................................................................................93 
7.2 
NIH Intramural IRB and Clinical Director (CD) Reporting ...........................................93 
7.2.1 
NIH Intramural IRB and NCI CD Expedited Reporting of Unanticipated 
Problems and Deaths.................................................................................................93 
7.2.2 
NIH Intramural IRB Requirements for PI Reporting at Continuing Review ...........93 
7.2.3 
NIH Intramural IRB Reporting of IND Safety Reports ............................................94 
7.3 
IND Sponsor Reporting Criteria .....................................................................................94 
7.3.1 
Reporting Pregnancy .................................................................................................94 
7.4 
Data and Safety Monitoring Plan ....................................................................................95 
7.4.1 
Principal Investigator/Research Team ......................................................................95 
7.4.2 
Sponsor Monitoring Plan ..........................................................................................95 
7.4.3 
Safety Monitoring Committee ..................................................................................96 
8 
STATISTICAL CONSIDERATIONS..................................................................................96 
8.1 
Primary endpoints ...........................................................................................................96 
8.1.1 
Part A ........................................................................................................................96 
8.1.2 
Part B: .......................................................................................................................97 
8.2 
Determination of Sample Size ........................................................................................98 
9 
HUMAN SUBJECTS PROTECTIONS ...............................................................................98 
9.1 
Rationale For Subject Selection ......................................................................................98 
9.2 
Participation of Children .................................................................................................99 


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9.3 
Participation of Subjects Unable to Give Consent ..........................................................99 
9.4 
Evaluation of Benefits and Risks/Discomforts ...............................................................99 
9.4.1 
Risks from Study Drugs ............................................................................................99 
9.4.2 
Risks of study procedures .......................................................................................100 
9.5 
Risks/Benefits Analysis ................................................................................................100 
9.6 
Consent and Assent Process and Documentation .........................................................100 
9.6.1 
Consent procedure for non-English speaking patients............................................101 
9.6.2 
Telephone consent procedure .................................................................................101 
10 
PHARMACEUTICAL INFORMATION ...........................................................................101 
10.1 LMB-100 (IND # 123332) ............................................................................................102 
10.1.1 Source .....................................................................................................................102 
10.1.2 Toxicity ...................................................................................................................102 
10.1.3 Formulation and preparation ...................................................................................103 
10.1.4 Stability and Storage ...............................................................................................104 
10.1.5 Administration procedures ......................................................................................104 
10.1.6 Incompatibilities .....................................................................................................104 
10.2 Nab-paclitaxel ...............................................................................................................105 
10.2.1 Source .....................................................................................................................105 
10.2.2 Toxicity ...................................................................................................................105 
10.2.3 Formulation and preparation ...................................................................................106 
10.2.4 Stability and Storage ...............................................................................................107 
10.2.5 Administration procedures ......................................................................................108 
10.2.6 Incompatibilities .....................................................................................................108 
11 
REFERENCES ...................................................................................................................109 
12 
APPENDICES ....................................................................................................................114 
12.1 Appendix A – Performance Status Criteria ..................................................................114 
12.2 Appendix B – Cockcroft-Gault Formula for Calculation of Creatinine Clearance ......115 
12.3 Appendix C: Sample Chemotherapy Notes ..................................................................116 
12.3.1 For Part A ................................................................................................................116 
12.3.2 For Arm B1 .............................................................................................................117 
12.3.3 For Arm B2 .............................................................................................................118 
 


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1 
INTRODUCTION 
1.1 
STUDY OBJECTIVES 
1.1.1 Primary Objective: 
1.1.1.1 Arm A1 (Phase I, short infusion): 
x To determine the maximum tolerated dose (MTD) of short infusion LMB-100 when given 
in combination with nab-paclitaxel to participants with advanced pancreatic cancer  
1.1.1.2 Arm B1 (Continuous infusion single agent lead-in: 
x To determine the maximum tolerated dose of LMB-100 given in a continuous infusion 
format over 24 - 96 hours to patients with advanced solid tumors that express mesothelin 
1.1.1.3 Arm B2 (Continuous infusion combination therapy): 
x Establish a tolerated dose of LMB-100 given by continuous infusion in combination with 
nab-paclitaxel chemotherapy in participants with advanced pancreatic cancer 
1.1.1.4 Arm A2 (Phase II short infusion): 
x To determine the objective response rate (PR+CR) according to RECIST 1.1 criteria of short 
infusion LMB-100 in combination with nab-paclitaxel chemotherapy in participants with 
advanced pancreatic cancer 
1.1.2 Secondary Objectives: 
1.1.2.1 All Phases 
x 
To determine the safety and tolerability of LMB-100 or the combination with nab-
paclitaxel in participants with advanced pancreatic cancer  
x 
To assess additional measures of efficacy including: 
x 
 change in the CA 19-9 serum marker with treatment (or other appropriate tumor 
marker for Arm B1 [Single Agent Lead-in]) 
x 
objective response rate (ORR) in Arms A1, B1 and B2  
x 
disease control rate at 4 months (as defined in section 6.3.7)  
x 
progression free survival  
x 
overall survival  
x 
To define the pharmacokinetics of LMB-100 in the absence and presence of participant 
LMB-100 anti-drug antibodies (ADAs)  
1.1.3 Exploratory Objectives: 
Both phases 
x 
To identify a threshold titer of participant LMB-100 ADAs that predicts inadequate 
drug exposure 
x 
To examine the relationship between MSLN expression and response to treatment 
x 
To identify the mechanism for Pseudomonas endotoxin-mediated capillary leak 
syndrome 
x 
To examine the effect of immunotoxin treatment on the microenvironment in the Part 


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B portion of the study 
x 
To determine the effect of LMB-100 on the pharmacokinetics of nab-paclitaxel 
x 
To correlate plasma concentrations of nab-paclitaxel to clinical response, toxicity, 
pharmacogenetic analyses and pharmacodynamic endpoints 
x 
To assess the genotype of the most relevant drug metabolizing enzymes and transporters 
(DMET) 
1.2 
BACKGROUND AND RATIONALE 
1.2.1 Background on Disease 
Pancreatic cancer is the fourth most common cause of cancer death in the United States, claiming 
more than 40,000 lives each year. Incidence nearly equals mortality with just 6% of patients living 
five years beyond their diagnosis. Most patients are diagnosed at an advanced stage, but even 
patients with early stage disease have a long term survival of less than 20%.[1] Combination 
chemotherapy with FOLFIRINOX provides the greatest survival advantage for patients who have 
advanced disease, but the median overall survival (OS) for this regimen does not reach one year 
and most pancreatic cancer patients are not fit enough to tolerate it.[2] Gemcitabine with NAB-
paclitaxel is an alternative regimen and extends median overall survival to 8.5 months from 6.7 
months with gemcitabine alone.  The response rate (RR) to this regimen in the first-line is 23% 
with less than 1% of patients achieving a complete response (CR).[3] Prospective and retrospective 
cohort studies have estimated a 17% RR to this regimen when given in second-line to good 
performance status patients following FOLFIRINOX.[4, 5] Single agent gemcitabine remains the 
recommended treatment for patients with poor performance status. Erlotinib is the only targeted 
therapy with efficacy against this disease and extends median OS by approximately 10 days when 
added to gemcitabine at the expense of significant toxicity.[6] Median survival of patients able to 
receive second line therapy is approximately 3-6 months.[7] New paradigms for the effective 
treatment of pancreatic cancer are sorely needed.   
1.2.2 Mesothelin (MSLN) as a therapeutic target 
MSLN is a cell surface glycoprotein that is a differentiation antigen for mesothelial cells; 
expression in normal tissues is confined to the pleura, pericardium and peritoneum. The normal 
function of MSLN is unknown. MSLN is expressed by a wide variety of solid tumors (Table 1) 
Expression of MSLN in PDAC has been reported in several published studies and ranges from 86 
to 100%.[8-10] Please see Table 2 below for a summary of this expression. MSLN is also expressed 
in tumors from genetically engineered mouse models (GEMMs) of PDAC, including the KPC 
model.[11]  MSLN is specifically a marker of adenocarcinoma in the human disease and is not 
expressed in preceding pre-malignant stages of tumor development.[12] Increased MSLN 
expression in early stage PDAC participants who undergo surgical resection confers decreased 
survival.[13] MSLN expression is also associated with more aggressive disease in 
cholangiocarcinoma, lung, ovarian and breast cancers.[14-17] In pancreatic cancer cell lines, 
overexpression of MSLN increases proliferation, motility and invasion and decreases survival of 
mice bearing tumors grown from these cells.[18] These properties make MSLN an attractive target 
for anti-neoplastic therapies, and more than five anti-MSLN agents are currently undergoing 
clinical testing.  


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Table 1. Prevalence of MSLN expression by tumor type[19] 
 
Table 2. Pancreatic ductal adenocarcinoma (5B2 antibody)[10] 
 


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1.2.3 Recombinant Immunotoxins (RITs)  
1.2.3.1 Mechanism and structure of RITs 
RITs are antibody-based therapeutics that carry a 
toxin payload.  RITs that target MSLN contain a 
genetically engineered variant of Pseudomonas 
exotoxin A (PE) in which the native cell-binding 
domain of PE is replaced by a MSLN-binding 
antibody fragment. In this way, the RIT binds 
specifically to MSLN on the cell surface and gets 
internalized through endocytic processes. In the 
cytosol, PE catalyzes an irreversible, inactivating 
modification of eukaryotic Elongation Factor-2 
(eEF-2). This prevents the elongation step of protein 
synthesis, halting production of new cellular 
proteins, a stressor that triggers apoptosis. This 
mechanism of action results in cytotoxicity to both 
proliferating and non-dividing cells, therefore 
proper targeting is critical to the safety profile.[20]   
 
Tumor-targeted bacterial toxins that inhibit the protein synthesis of cancer cells have previously 
shown signs of preclinical and clinical efficacy. For instance, SS1P, a classical immunotoxin 
format molecule derived from mouse anti-mesothelin antibody SS1 and a 38 kDa PE toxin 
fragment (PE38) is one example. Besides SS1P, the most clinically advanced PE-based 
immunotoxins are moxetumomab pasudotox, a CD22-targeted fusion protein in development by 
Astra Zeneca/ Medimmune, and LMB2, a CD25-targeted PE fusion protein developed by the 
National Cancer Institute (NCI). Both agents have shown encouraging signs of efficacy in different 
hematological malignancies and are currently in Phase II and III clinical trials. Denileukin difitox 
is the only immunotoxin approved by the US Food and Drug Administration (FDA); a fusion 
protein of diphtheria toxin with interleukin-2 that is clinically used for intravenous treatment of 
cutaneous T cell lymphoma.  
1.2.3.2 Rationale for the development of LMB-100 
The clinical use of SS1P, and of immunotoxins in general, has been hampered mainly by two key 
issues: firstly their high immunogenicity and secondly that they cause vascular leak syndrome 
(VLS) as a common severe side effect that is clinically difficult to manage.  LMB-100 (see Figure 
1 for structure) is a next generation PE-fusion protein that has been protein-engineered to 
maximally reduce its immunogenicity and its propensity to induce VLS by: 
 
1. Using a fully humanized Fab fragment derived from the anti-mesothelin antibody SS1 for 
tumor targeting 
2. Substituting the bulk of domain II (residues 251–273 and 284–394 of native PE) by an 
extended furin cleavable linker whose sequence is devoid of any T cell neoepitopes 
3. Deimmunizing domain III of PE, which has the catalytic activity for ADP-ribosylation by 
introducing 7 point mutations that silence B- and T-cell epitopes 
 
Figure 1: RIT Structure 


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Classical PE-based immunotoxins, such as SS1P, contain a 38 kD fragment of the exotoxin 
encompassing the so called translocation domain II and the catalytic domain III. Omission of the 
domain II from LMB-100 has not only removed a highly immunogenic 14 kD portion of PE that 
contains the main T-cell epitopes,[21] but has also resulted in reduced incidence of VLS.[22] 
1.2.3.3 Nonclinical summary of previous generation MSLN-targeted RIT SS1P 
The SS1P molecule is composed of the VL from SS1, an affinity-matured derivative of an anti-
MSLN monoclonal antibody, disulfide bonded to a fusion of VH of SS1 with PE38. Compared to 
wild type toxin, the PE38 fragment lacks the cell-binding domain I (residues 1–252) as well as the 
toxin portion encompassing positions 365380. 
Viability of tumor cell lines expressing mesothelin is potently reduced by treatment with SS1P, 
resulting in half-maximal inhibitory concentration values (IC50) in the single digit ng/mL range 
(equivalent to ~10 pM) or even lower for some tumor cell lines, while mesothelin-negative cancer 
cells are insensitive to SS1P even at 100 ng/mL.[23, 24] 
Using primary tumor cells from ascites or pleural effusion from nine mesothelioma patients, Zhang 
et al.[25] found that in most cases mesothelin expression was lost upon in vitro culture. However, 
for the few samples that retained mesothelin positivity, the mesothelin level on the cell surface, 
which ranged from 600200,000 sites/cell, correlated with SS1P sensitivity. 
In mice, SS1P had severe off-target toxic effects on the liver, limiting the maximum tolerated dose 
(MTD) in a 3 uper week QOD schedule to d0.5 mg/kg.[22] Using MTDs and the 3 uper week 
QOD regimen, SS1P was shown to have significant monotherapy efficacy in xenograft models of 
the NCI-H226 cell line (derived from pleural effusions of a mesothelioma patient).[26] 
Monotherapy anti-tumor efficacy of SS1P has also been shown in xenografts of the stably 
transfected A431 K5 cell line,[27] that expresses very high levels of mesothelin on the cell surface 
(25 million molecules per cell). In the same study, synergistic antitumor activity was found for 
the combination of SS1P with paclitaxel in vivo but not in vitro. The underlying mechanism has 
subsequently been claimed to be related to improved tumor penetration and intratumoral 
distribution of SS1P associated with a paclitaxel-mediated reduction of shedding of mesothelin 
from the tumor cells.[28, 29] 
When given to BALB/c mice as IV bolus injections (100 μL/mouse) at doses of 0.125 or 0.4 
mg/kg, SS1P has been reported to have a serum half-life of about 26 minutes, reaching a maximum 
serum concentration of 3.4 Pg/mL at 30 minutes post-injection. The mean residence time has been 
reported as 0.64 minutes and the area under the plasma concentration curve as 0.36 minutes 
mg/mL.[30] 
Toxicology studies of SS1P were conducted in cynomolgus monkeys with different doses and 
schedules, including a 1 mg/kg 3 uper week QOD schedule. Decreased appetite and physical 
activity was observed in animals treated with the 1 mg/kg dose level of SS1P. Necropsy studies of 
SS1P-treated cynomolgus monkeys showed dose-dependent, microscopic inflammation of serosal 
membranes, suggesting that pleuritis and/or pericarditis could be dose limiting.[31] 
 


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1.2.3.4 Clinical Summary of previous generation MSLN-targeted RIT SS1P 
SS1P has been tested in a clinical setting by the NCI in the United States.[31] The related adverse 
events (AEs) included pleuritic pain, VLS, hypoalbuminemia, weight gain, fatigue, fever, and 
edema. In an initial Phase I trial, a cohort of 17 patients received SS1P QOD u6 doses. The MTD 
was 18 Pg/kg and the dose-limiting toxicities (DLTs) included Grade 3 urticaria (1 patient) and 
Grade 3 VLS (2 patients). To allow further SS1P dose escalation, another 17 patients were treated 
on a QOD u3 doses schedule with the MTD reaching 45 μg/kg. The DLT observed was Grade 3 
pleuritis (2 of 2 patients treated at 60 Pg/kg and 1 of 9 patients treated at 45 μg/kg). A second trial 
evaluated the safety and PK profile of SS1P given as continuous infusion for 10 days.[31] The MTD 
in this study was 25 μg/kg/day u10 doses, where 1 of 6 patients had a DLT due to reversible VLS. 
The most common adverse events were edema (71%), hypoalbuminemia (62%), fatigue, (62%), 
weight gain/VLS (54%), nausea (46%), fever (46%), hypotension (38%), and allergy/rash (33%). 
The clinical efficacy of SS1P in humans has been limited to date, with 4 minor responses out of 
33 evaluable patients in the initial IV bolus monotherapy trial[31] and 1 partial response out of 24 
patients in the continuous infusion trial.[31] This is most likely due to the immunogenicity of the 
compound, which led to the development of neutralizing ADAs in the vast majority of the patients 
after 1 cycle of therapy in both the IV bolus and the continuous infusion trials. This hypothesis is 
supported by an exploratory trial currently ongoing by the NCI in which patients are pretreated 
with an immunosuppressive chemotherapy regimen (pentostatin and cyclophosphamide) for 14 
days prior to administration of SS1P. In this trial, 3 out of 10 patients achieved a partial response 
and another 3 patients achieved durable disease stabilization.[31, 32] One of the three patients 
achieving a partial response did so after receiving just two cycles of SS1P before developing 
neutralizing anti-SS1P antibodies and coming off treatment. In addition, a recent Phase1b study 
was published where SS1P was given with pemetrexed and cisplatin in advanced malignant pleural 
mesothelioma (MPM). SS1P was shown to be safe and well tolerated and exhibited significant 
antitumor activity in patients with unresectable, advanced pleural mesothelioma.[33] 
Based on the safety profile described previously for SS1P when given as single agent or in 
combination, the potential risks of treatment with LMB-100 were expected to include VLS, 
hypoalbuminemia, edema, pleuritis, infusion-related reactions, and immunogenicity. Precautions 
for diagnosis, monitoring, prevention, and treatment of adverse events will be provided in the 
Phase I studies. 
1.2.4 LMB-100 
1.2.4.1 Nonclinical Studies of LMB-100 
1.2.4.1.1 Nonclinical Pharmacology 
In vitro LMB-100 inhibited viability of a variety of mesothelin-positive cancer cell lines at 
effective concentrations typically around 14 pM (~1 ng/mL). The cytotoxic potency of LMB-100 
varied between 0.35 ng/mL in primary mesothelioma cells (RH21) and 15.7 ng/mL in an 
adenosquamous lung carcinoma cell line (H596). Binding studies showed that while the Fab 
fragment did not bind to mouse or rat mesothelin, the binding affinities to cynomolgus and human 
mesothelin were identical. In agreement with this, LMB-100 induced apoptosis in mesothelin-
positive primary cynomolgus pericardial cells and significantly impaired viability of HEK293 cells 
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cells. In addition, control experiments showed that free PE24 was 1001000 fold less potent on 
mesothelin-positive target cell lines, confirming low cytotoxic potential of PE24 lacking a 
targeting moiety. 
Animal studies demonstrated that a single cycle of LMB-100 treatment given at an optimal dose 
of approximately 2 mg/kg, 3 uper week, every other day (QOD) achieved tumor regressions in 
subcutaneous xenografts of adenosquamous lung carcinoma (H596) in severe combined 
immunodeficient (SCID) beige mice. Three consecutive treatment cycles, given with 1 week 
breaks in between, led to massive shrinkage of large tumors with an average initial volume of 600 
mm3. Tumor regressions in monotherapy were also achieved when treating subcutaneous 
xenografts of mesothelioma (NCI-H226), gastric (MKN-28), and triple negative breast (HCC70) 
cancer cell lines in athymic nude mice. Highly synergistic antitumor efficacy was observed in 
combination therapy with paclitaxel when treating subcutaneous xenografts of the recombinant 
high mesothelin expressing A431H9 cell line or the pancreatic cancer cell line KLM1. These 
results support evidence that LMB-100 may provide clinical benefit to participants with cancer. 
1.2.4.1.2 Combination of taxane with LMB-100  
A favorable in vivo interaction between paclitaxel and SS1P was first described by the Pastan lab 
nearly ten years ago[27] Pre-administration of paclitaxel was demonstrated to increase the amount 
of immunotoxin internalized by tumor cells and to reduce levels of shed MSLN in the intra-tumoral 
environment so that more immunotoxin could 
bind tumor cells.[28] Consistent with this 
mechanism, no synergy was observed in vitro.  A 
similar effect has been observed with LMB-
100.[34, 35] The effect is even more pronounced 
with NAB-paclitaxel in a pancreatic cancer model, 
where all combination treated mice develop 
complete regressions of their tumors (Figure 2). 
Strikingly, the tumors never regrew in most of the 
animals. Similar results have been seen with in 
A431 cells stably overexpressing MSLN and also 
in tumors grown from primary mesothelioma 
cells. Research in our laboratory has demonstrated 
that this synergistic interaction can also be 
observed in vitro suggesting that a direct 
mechanism accounts for at least part of the effect 
(data not shown, manuscript in preparation).  The 
exact mechanism remains under investigation. 
These data support testing of this combination in 
the clinic as it may have clinical benefit for 
pancreatic cancer patients.  
Figure 2 


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17 
 
1.2.4.1.3 Pharmacokinetics in Animals 
The pharmacokinetics (PK) of LMB-100 were tested in cynomolgus monkeys following single IV 
administration at doses ranging from 0.03 mg/kg to 0.3 mg/kg. Two different enzyme-linked 
immunosorbent based formats were used for analyzing plasma levels of LMB-100; free and total 
drug assay (where the total drug assay was the sum of free LMB-100 and LMB-100 complexed 
with binding molecules). LMB-100 showed a relatively rapid plasma clearance and a volume of 
distribution at steady-state similar to the plasma volume. Within the dose range tested, non-linear 
PK was observed for free drug with an extended half-life at higher doses (mean terminal half-life 
approximately 0.6 hours at 0.3 mg/kg compared to 0.3 hours at 0.03 mg/kg) suggesting saturation 
of MSLN-mediated clearance pathways. Clearance of total drug was consistently lower than that 
for free drug implying the presence of soluble binding partners such as soluble mesothelin and 
ADAs. Induction of anti-drug antibodies (ADA) responses was frequently detectable in all dose 
groups tested. Overall, given the limited predictive value of immunogenicity reactions in animals 
to human, a risk for immunogenicity in humans cannot be excluded. Toxicokinetics after repeated 
IV dosing in cynomolgus monkeys demonstrated an increase in total exposure in a dose 
proportional manner between 0.1 mg/kg and 3.0 mg/kg. No accumulation was observed over 5 
consecutive days of treatment or over two dosing cycles with 3 uper week dosing. Almost all 
monkeys developed ADAs upon treatment, while induction of high ADA levels impaired the 
exposure of free drug. In some cases, the induction of ADAs may have induced a slight increase 
in exposure 
The relationship between systemic drug exposure and anti-tumoral activity of LMB-100 was 
investigated on human lung cancer NCI-H596 xenograft growth in female SCID beige mice. Free 
and total drug profiles were similar in mice. Modeling estimated a plasma concentration of 6800 
ng/mL (r36%) to trigger a half maximal rate of tumor regression. Concentrations of LMB-100 
above this level resulted in potent tumor regression after dosing. Normalized for exposure, SS1P 
was found to be ~3-fold more potent than LMB-100 in terms of tumor growth inhibition. 
1.2.4.1.4 Toxicology and Safety Pharmacology 
The toxicological profile of LMB-100 was assessed after repeated intravenous administration to 
cynomolgus monkeys, the only relevant species, for a maximum of 5 daily doses for one week or 
2 cycles with QOD u3 dosing, separated by a 9 day dosing free period. Four daily doses of 3 
mg/kg exceeded the maximum tolerated dose with animals being found in moribund condition, 
indicated by clinical signs of hypoactivity, hunched posture, ataxia, and tremors. There were no 
histopathological changes to account specifically for the deteriorating physical condition of these 
animals. 
Histopathological findings such as kidney tubular degeneration/regeneration and changes at 
serosal-lining tissues were observed at lower doses as well. In general, administration of LMB-
100 resulted in both on- and off-target toxicities. 
On-target effects were observed on serosal-lining tissues, consistent with high expression of 
mesothelin. Mesothelium hypertrophy accompanied by subpleural cellular hypertrophy and 
serosal fibrin exudate was observed in the lung at doses t1 mg/kg. Mesothelium hypertrophy also 
occurred in heart (epicardium), spleen, and stomach. Off-target or non-specific toxicity included 
degeneration/regeneration of kidney tubular epithelium after repeated doses of t0.3 mg/kg. Local 
inflammatory findings at the injection sites were observed after administration of LMB-100 in 


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18 
 
several studies. Clinically, reddening of the skin, swelling, and skin being warm to touch or flaky 
injection sites were reported. In the 2-cycle GLP study (3 intermittent doses over a 5-day period, 
9-days apart), impaired movement of animals from all dose groups was likely related to injection 
site findings and an overall inflammatory profile. One female at 1 mg/kg was sacrificed early on 
Day 4 after 2 doses due to severe clinical signs most likely attributed to inflammatory changes at 
injection sites resulting in moribundity of the animal. Clinically observed inflammatory changes 
correlated with histopathological changes such as hemorrhages and/or acute inflammation at the 
injection sites and clinical pathology changes consistent with an overall inflammatory profile 
(increases in monocytes, neutrophils, CRP, and haptoglobin). Microscopic changes reversed 
completely after the 4-week recovery period in the 2-cycle GLP study. The Highest Non Severely 
Toxic Dose in this study was 0.3 mg/kg, which resulted in a mean AUC for total drug of 16.0 
μg·h/mL (study day 1, preliminary data). In a subsequent 1 cycle GLP study (QOD u3 dosing), 
markedly reduced Injection site findings were observed after administration of a batch with 
reduced levels of product related modifications of LMB-100. In this study, the HNSTD was 1 
mg/kg, resulting in an AUC for total drug of 27.4 and 23.6 μg·h/mL after the first and third dose 
(preliminary data). 
The potential of LMB-100 to induce off-target vascular leak in lungs was assessed in female Wistar 
rats. Mild perivascular edema was reported microscopically, but did not correlate with 
macroscopic or serum chemistry findings consistent with VLS. Ultrasound evaluation in the NHP 
GLP study revealed minimal accumulation of pericardial fluid with limited biological significance 
at the highest dose of 1 mg/kg. No appreciable accumulation of pleural fluid was observed at 
necropsy. 
In vitro evaluation of LMB-100 in human whole blood assay indicated a low risk for cytokine-
mediated infusion related reaction (IRR)/cytokine release syndrome (CRS) upon first 
administrations. LMB-100 caused no hemolysis when added to human peripheral blood up to the 
highest concentrations of 0.5 mg/L. 
1.2.4.2 Previous Roche clinical study of LMB-100  
Initial clinical testing of LMB-100 was performed by Roche in a multi-center international first in 
human trial (NCT02317419). The primary objective of the Phase I study was to define the safety 
and tolerability (including the MTD) and pharmacokinetics of the drug in participants with MSLN-
expressing metastatic or locally advanced solid tumors for whom no standard therapy was 
available. Secondary objectives included determination of the RP2D and schedule, exploration of 
preliminary anti-tumor activity by assessing objective response rate (ORR) and disease control 
rate (DCR), and assessment of pharmacodynamic effects.  
A total of 15 participants were enrolled onto the study before termination. Median age of 
participants was 60.8 years and 53.3% were female.  All participants had received prior anti-cancer 
therapy for their tumors. Enrolled participants had advanced mesothelioma (7), ovarian cancer (3), 
pancreatic cancer (3), and gastroesophageal cancer (2). Tumors from 13 of the 15 participants 
treated had moderately to strongly positive MSLN expression as measured by central IHC analysis.  
LMB-100 was administered intravenously on Days 1, 3 and 5 of a 21-day treatment cycle. No pre-
medications were given. Treatment was initiated at the MTD of SS1P, 45 mcg/ kg. Five different 
dose levels were tested (see Table 3). Dose limiting toxicity (DLT) was reached at 250 mcg/kg, 
with 2 of 4 participants treated at this dose level experiencing vascular leak syndrome (grade 2 and 


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19 
 
grade 4). Additional toxicities were associated with this toxic dose level. At this point, a sixth 
cohort receiving 200 mcg/kg of study drug was enrolled, however, the study was terminated by 
the company before the two accrued participants completed cycle 1 of therapy. Therefore, the 
single agent MTD was not determined.   
Table 3. LMB-100 Dose escalation study- NCT02317419 
Dose (mcg/kg) 
No. of patients 
Pts with DLT 
45 
1 
0 
65 
1 
0 
100 
3 
0 
170 
4 
0 
200 
2 
NE 
250 
4 
2 
DLTs were vascular leak syndrome and proteinuria 
NE, Study terminated before DLT assessment period was complete and 
patients only received single dose of RG7787 
1.2.4.2.1 LMB-100 Adverse Events 
Overall, 14 participants (93.3%) experienced at least one AE.  The most common AEs were 
hypoalbuminemia (60.0%), fatigue (53.3%), peripheral edema (53.3%), nausea (46.7%), pyrexia 
(40.0%), decreased appetite (33.3%), dyspnea (33.3%), and myalgia (33.3%). SAEs included 
vascular leak syndrome, pyrexia, atrial flutter, infusion related reaction, arthritis, 
glomerulonephritis minimal lesion and dyspnea.  No participants experienced an AE that led to 
withdrawal of study treatment. Four participants experienced a total of 8 infusion-related reactions 
that were independent of drug dose level.  All of these AEs were non-serious and resolved within 
approximately 1 hour of onset. Pre-medication for infusion reaction was administered to these 
participants prior to subsequent doses of LMB-100. Two suspected Type III hypersensitivity 
reactions were observed. These consisted of arthritis (1) and rash with fever (1), both of which 
were fully reversible. When other AEs attributed to the study drug are presented by dose level of 
drug, it becomes clear that toxicity was strongly associated with the 250 mcg/kg dose level at 
which DLT was reached (see Table 4 and Table 5 which are adapted from Roche Final Study 
Report, “Summary of Adverse Events Related to Study Medication, Safety-Evaluable Patients 
Protocol: BP29387”). Two of four patients treated at 250 mcg/kg experienced serious VLS which 
manifested with hypotension, respiratory compromise, serosal membrane reaction and 
hyponatremia as well as the hypoalbuminemia and edema that can be seen with mild VLS. Other 
symptoms associated with the DLT dose were fatigue, nausea, vomiting, decreased appetite and 
mild elevation of transaminases. In summary, safety and tolerability of LMB-100 were as 
expected. 


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20 
 
Table 4: Grade 3 or 4 Adverse Events Attributed to LMB-1001 
Dose (mcg/kg) 
45 
65 
100 
170 
250 
ALL 
# of patients treated 
1 
1 
3 
4 
4 
13 
Vascular leak (gr 4) 
- 
- 
- 
- 
1 
1 
Hyponatremia (gr 3) 
- 
- 
- 
- 
1 
1 
Anemia (gr 3) 
- 
- 
- 
1 
- 
1 
Decreased lymphocytes (gr 3) 
- 
- 
- 
- 
1 
1 
Dyspnea (gr 3) 
- 
- 
- 
- 
1 
1 
Infusion-related reaction (gr 3) 
- 
- 
1 
- 
- 
1 
Arthritis (gr 3) 
- 
- 
1 
- 
- 
1 
1 adapted from Clinical Study Report No 1066017 from Roche dated December 2015, “Summary of Adverse Events 
Related to Study Medication, Safety-Evaluable Patients Protocol: BP29387” See pages 175-193 of the report. 
Table 5: Adverse Events attributed to LMB-1001 
Dose (mcg/kg) 
45 
65 
100 
170 
250 
ALL 
# of patients treated 
1 
1 
3 
4 
4 
13 
Vascular Leak 
- 
- 
1 
1 
2 
4 
grade 3 or 4 vascular leak 
- 
- 
- 
- 
1 
1 
hypotension 
- 
- 
- 
- 
2 
2 
hypoalbuminemia 
- 
1 
3 
2 
3 
9 
peripheral edema 
1 
1 
3 
2 
4 
11 
facial edema 
- 
1 
2 
- 
1 
4 
weight gain 
- 
- 
1 
- 
1 
2 
hyponatremia 
- 
- 
- 
- 
3 
3 
hypophosphatemia 
- 
- 
- 
- 
1 
1 
dyspnea 
- 
1 
- 
- 
2 
3 
Infusion related reaction 
- 
- 
2 
- 
2 
4 
Constitutional  
  
  
  
  
  
  
fatigue 
- 
- 
- 
1 
4 
5 
asthenia 
- 
- 
3 
- 
- 
3 
fever 
1 
- 
2 
1 
2 
6 
Musculoskeletal 
  
  
  
  
  
  
myalgia 
- 
- 
1 
1 
2 
4 
arthralgia 
1 
- 
- 
- 
1 
2 
arthritis 
- 
- 
1 
- 
- 
1 
muscle spasm 
- 
- 
- 
1 
- 
1 
Cardiac 
  
  
  
  
  
  
pericardial effusion 
- 
- 
- 
- 
1 
1 
Atrial flutter 
- 
- 
- 
1 
- 
1 


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21 
 
Dose (mcg/kg) 
45 
65 
100 
170 
250 
ALL 
# of patients treated 
1 
1 
3 
4 
4 
13 
Renal Disorders 
glomerulonephritis minimal 
- 
- 
- 
1 
- 
1 
proteinuria 
- 
- 
- 
1 
1 
2 
Creatinine increase 
- 
- 
- 
- 
2 
2 
Gastrointestinal 
  
  
  
  
  
  
decreased appetite 
- 
1 
- 
1 
2 
4 
nausea 
1 
- 
1 
1 
4 
7 
abdominal pain 
- 
1 
- 
1 
1 
3 
diarrhea 
1 
- 
1 
- 
- 
2 
vomiting 
- 
- 
- 
- 
2 
2 
abdominal distension 
- 
1 
- 
- 
- 
1 
constipation 
- 
- 
- 
1 
- 
1 
dyspepsia 
- 
- 
- 
1 
- 
1 
AST increase 
- 
- 
- 
- 
2 
2 
Hematologic 
  
  
  
  
  
  
anemia 
- 
- 
- 
1 
- 
1 
decreased lymphocytes 
- 
- 
- 
- 
1 
1 
Total Grade 3 or greater 
- 
- 
2 
1 
2 
5 
Orange highlighting indicates that one of the patients experienced a grade 3 or 4 toxicity in this category.  Please 
note that there was only 1 patient who experienced a high grade toxicity of each type. 
1 adapted from Clinical Study Report No 1066017 from Roche dated December 2015, “Summary of Adverse 
Events Related to Study Medication, Safety-Evaluable Patients Protocol: BP29387” See pages 175-193 of the 
report.” 
1.2.4.2.2 Anti-Drug Antibodies (ADAs) and LMB-100 Drug Levels 
Twelve participants were evaluable for efficacy.  The best confirmed overall response was stable 
disease in 3 participants.  A Roche-developed ELISA test was used to retrospectively assess anti-
drug antibody (ADA) titers. 5 of 15 participants had detectable ADAs at study enrollment while 
the remaining participants did not, however, the remaining participants developed detectable 
ADAs by the end of Cycle 2. Immunogenicity of LMB-100 did affect serum drug levels.  These 
data are summarized in Figure 3. All evaluable participants achieved expected serum drug levels 
during the first cycle of treatment. Six of 7 participants without pre-existing ADAs achieved 
effective drug levels during the second cycle, while 0 of 2 participants with pre-existing ADAs 
did. One of 3 participants that received a third cycle of treatment also achieved effective drug 
levels during this cycle.  A positive test for ADAs did not definitively predict poor blood levels in 
the subsequent cycle (see patient 1101 in Table 7 ). In summary these data show that the presence 
of ADAs is not predictive of ability to achieve measurable LMB-100 concentration in the serum, 
which is the most important parameter for drug efficacy. 
 


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22 
 
Figure 3: LMB-100 ADAs and Blood Levels 
 
Table 6: LMB-100 drug levels and ADAs in patients WITH pre-existing ADAs 
 
 
Cycle 1 
Cycle 2 
Patient  
Dose 
(mcg/kg) 
ADA 
(Day1) 
Cmax 
(ng/ml) 
ADA 
(Day1) 
Cmax 
(ng/ml) 
dC1/dC2 
(%) 
1001 
45 
2700 
620 
196830 
0 
-100 
1201 
100 
8100 
495 
196830 
0 
-100 
1501* 
250 
2700 
3730 
196830 
- 
- 
1003 
250 
900 
2960 
196830 
- 
- 
* Patient’s treatment stopped due to study closure 
Table 7: LMB-100 drug levels and ADAs in patients WITHOUT pre-existing ADAs 
Cycle 1 
Cycle 2 
Cycle 3 
Patien
t  
Dose 
(mcg/kg) 
ADA 
(Day1) 
Cmax 
(ng/ml) 
ADA 
(Day1) 
Cmax 
(ng/ml) 
dC1/dC 
(%) 
ADA 
(Day1) 
Cmax 
(ng/ml) 
dC1/dC 
(%) 
1002 
65 
0 
1150 
8100 
711 
-38 
- 
- 
- 
1401* 
100 
0 
1790 
0 
1610 
-10 
24300 
267 
-85 
1402 
100 
0 
1650 
0 
1360 
-18 
8100 
0 
-100 
1101* 
170 
0 
2760 
300 
3950 
43 
900 
3490 
26 
1202 
170 
0 
3040 
0 
1940 
-36 
- 
- 
- 
1301 
170 
0 
3430 
72900 
527 
-85 
- 
- 
- 
1403 
170 
0 
1930 
900 
1550 
-20 
- 
- 
- 
1102* 
250 
0 
5480 
0 
4770 
-13 
- 
- 
- 
1302 
250 
0 
4340 
- 
- 
- 
- 
- 
- 


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23 
 
* Patient’s treatment stopped due to study closure 
ADA data are from Roche "Bioanalytical Report (ADA) for Clinical Study BP29387“with ADA time 
point codes translated as specified in the BP29837 Lab Manual Version 1.0. Cmax data were taken from 
the Roche final study report. 
 
1.2.4.2.3 Comparison of toxicity and immunogenicity of LMB-100 to SS1P  
In the Roche Phase 1 trial, LMB-100 was safely administered to four patients at 170 mcg/kg 
without DLT.  This is nearly four times the maximum tolerated dose (MTD) of SS1P.  Most 
patients without pre-existing ADAs were able to achieve effective drug levels of LMB-100 for 2 
cycles, unlike what has been seen previously with SS1P (see Figure 4). These data demonstrate 
that LMB-100 is both less toxic and less immunogenic than SS1P.  
Figure 4: LMB-100 vs SS1P[31] Cycle 2 Blood Levels 
 
p>0.001 by two tailed Fisher’s exact test 
1.2.4.3 NCI Phase I study of LMB-100 in patients with malignant mesothelioma 
Clinical testing of LMB-100 in a second single agent study has recently been completed.  In this 
trial, LMB-100 given by short infusion dosing was assessed in 10 patients with malignant 
mesothelioma (NCT02798536). Doses of 170 mcg/kg and 140 mcg/kg given as a 30-120 minute 
infusion every other day x3 doses were tested.  Reversible renal toxicity that prolonged 
hospitalization was observed at the 170 mcg/kg dose. Therefore, single agent short infusion MTD 
of 140 mcg/kg was established. Toxicities and peak drug levels have thus far been similar to what 
was seen in the completed Roche study.  Low serum LMB-100 levels and a high rate of infusion-
related reactions were observed after cycle 2, presumably due to the development of anti-LMB-
100 antibodies. 
1.2.4.4 Results in current study (16C0128 as of 16 July 2018) 
Part A – short infusion 
As of 7/16/2018, 14 subjects have been enrolled to receive escalating doses of LMB-100 in 
combination with a fixed dose (125 mg/m2) of nab-paclitaxel. LMB-100 was administered on days 
1, 3 and 5 of a 21-day cycle, while nab-paclitaxel was administered on days 1 and 8.  Six subjects 


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24 
 
received LMB-100 at dose level 1 (100 mcg/kg), of whom five were evaluable.  Of the five, two 
experienced DLTs of grade 3 myalgia. Therefore, per dose escalation rules, the next LMB-100 
dose level evaluated was 65 mcg/kg (dose level -1). Eight subjects have been enrolled, two of 
whom are deemed inevaluable. One of the six evaluable subjects experienced DLT of grade 3 
edema related to LMB-100 vascular leak.. This arm of the study (Arm A1) is now completed and 
closed to further accrual. Dose Level -1 is the recommended Phase 2 dose. Arm A2 has opened to 
accrual of patients at this dose and schedule. 
Part B – continuous infusion 
Subjects are being evaluated on Arm B1, dose exploration for continuous infusion LMB-100 
monotherapy.  Dose level 1 was discarded after treatment of 3 patients due to erratic PK results. 1 
of 6 patients at dose level 2 experienced DLT (grade 3 proteinuria). However, a planned dose de-
escalation was initiated to try to determine a better tolerated schedule since 3 of 6 patients at dose 
level 2 experienced non-DLT VLS resulting in >5 kg weight gain. As of 7/16/18, 6 participants 
have been treated at dose level 3 and completed the DLT period. None of the participants 
experienced significant VLS. 3 of the 6 participants received on the Day 1 and not the Day 4 dose 
of LMB-100 due to complications from their disease unrelated to study drug (question of partial 
small bowel obstruction, fever and hypotension from cholangitis, dehydration from nausea and 
vomiting due to overeating), and were therefore inevaluable. 1 of the 3 evaluable participants did 
not receive the Day 4 dose of LMB-100 due to transient grade 2 creatinine elevation that was 
attributed at least partially to study drug. This was considered an investigator-determined DLT 
since the patient was unable to receive the full course of treatment due to a study-drug related 
toxicity.   
1.2.5 Pharmacokinetics of LMB-100 and modeling of continuous infusion 
The initial Roche trial demonstrated that 
LMB-100 has an unexpectedly short drug 
half-life of 61 minutes as compared to 466 
minutes for the predecessor drug SS1P.[36] 
It is not known what factors contribute to 
the longer half-life in circulation of SS1P. 
Using these clinical pharmacokinetic data, 
estimations of individual pharmacokinetic 
parameters that would be achieved with a 
continuous 
infusion 
format 
can 
be 
calculated (see Table 8).  Using a one 
compartment population PK model, it is 
estimated through simulations that steady 
state maximum plasma concentration will 
be reached by 7 hours and that drug 
concentration will remain at this plateau 
level until the infusion is stopped (Figure 5). Peak plasma drug concentration (C max) using the 
continuous infusion is expected to be 92% lower than those seen following short infusion of the 
same amount of drug. Following completion of the continuous infusion, drug levels are expected 
to fall to near zero within 5 hours from the end of infusion. Results from patients enrolled onto the 
first Level of the Arm B1 Single Agent Lead-in have confirmed Cmax at or lower than that 
Figure 5 


Abbreviated Title: LMB-100 + Abrx in PDA 
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25 
 
predicted by the model and also that drug levels fall to near zero in less than 4 hours from the end 
of infusion. 
Table 8. LMB-100 drug exposure comparison 
 
 
1.2.6 Rationale for treating pancreatic cancer patients with LMB-100 and NAB-paclitaxel 
combination 
LMB-100 targets the cell surface antigen MSLN and is ineffective against tumor or normal cells 
that lack MSLN.  Expression of MSLN in pancreatic adenocarcinoma has been examined in 
several published studies and ranges from 86 to 100%,[8-10] making this tumor type a good target 
for LMB-100.  There is clearly an unmet need to identify improved therapies for this patient 
population as patients with metastatic pancreatic cancer have a median OS of less than one year 
with the best currently available therapies.  Pre-clinical studies have demonstrated that 
combination of LMB-100 with nab-paclitaxel results in synergistic anti-tumor efficacy.  NAB-
paclitaxel is part of an FDA approved regimen for patients with advanced pancreatic cancer and 
addition of LMB-100 to nab-paclitaxel may improve outcomes for these patients.  Given the 
overall poor prognosis of these patients, the potential to directly benefit from treatment with the 
combination regimen outweighs the risks of participating in the study. 
1.2.7 Rationale for assessing continuous infusion of LMB-100 
Clinical trials have shown that LMB-100 has a short half-life in humans of only 1 hour. Drugs 
with short half-lives can be administered by continuous infusion in order to improve drug 
exposure. Short half-life standard of care chemotherapies such as 5-FU and cytarabine are 
preferentially administered in this format. In the case of 5-FU the continuous infusion is preceded 
by a single bolus dose. Short half-life protein based therapeutics also appear to benefit from 
continuous infusion.  For example, the dual specificity CD19/ CD3 bispecific T cell engaging 
(BiTE) antibody construct, blinatumomab, has a half-life of just over 2 hours. In initial clinical 
trials using a 2-4 hour infusion given 2-3 times per week, the drug performed poorly and these 


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26 
 
trials were terminated early due to poor risk to benefit ratio.[37] Subsequently, the drug was 
reintroduced in a continuous infusion format. Decreased toxicity and significant efficacy, 
including complete remissions in patients with chemotherapy-refractory disease, were 
observed.[38] Blinatumomab has since been approved by the FDA for administration in the 
continuous infusion format.  
We hypothesize that sustained infusion of LMB-100 will be 
safer and more effective than short infusion. We expect LMB-
100 toxicity to decrease when given in the continuous infusion 
format because peak drug levels (Cmax) will be lower and this 
should reduce non-specific toxicity from the drug.  We expect 
greater efficacy because pre-clinical data suggest that duration 
of exposure to LMB-100 rather than peak dose may be more 
important for killing tumor cells. Specifically, we have found 
that sustained exposure of cultured cells to lower doses of 
LMB-100 can be more cytotoxic than treatments with higher 
doses given for shorter durations (Figure 6). In addition, 
previously published studies in mouse models with another 
short half-life immunotoxin demonstrated that continuous 
infusion of immunotoxin administered by means of surgically 
inserted intraperitoneal osmotic pump is less toxic; continuous 
infusion of these immunotoxins at MTD resulted in at least 2.5 
times higher AUC than could be achieved safely with a short 
infusion at MTD. Because of this, better anti-tumor efficacy was achieved with the continuous 
infusion dosing.[39]  
Instability of LMB-100 at 37°C precludes the ability to directly test its efficacy when administered 
continuously for several days in mouse pre-clinical tumor models. This is because the drug must 
be administered in a pump kept within the peritoneal cavity at mouse body temperature throughout 
the experiment and the drug loses activity within 24 hours when stored at these temperatures. 
However, preliminary data from pre-clinical studies performed by the LMB Immunotoxin group 
have shown increased efficacy and decreased toxicity when using 1) intraperitoneal continuous 
delivery of a related short half-life MSLN-targeted immunotoxin that is stable at 37°C and 2) bolus 
dosing of a long-half-life anti-MSLN immunotoxin that contains an albumin-binding domain that 
prolongs half-life. Both studies demonstrated increased anti-tumor efficacy compared to bolus 
dosing of LMB-100 (Figure 7).   
Figure 6 


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Version Date: 12/11/2018 
 
27 
 
Figure 7 
 
Continuous infusion dosing of the LMB-100 predecessor drug, SS1P, has been examined in a 
Phase I clinical trial. Although the long half-life of SS1P is expected to lessen the clinical impact 
of switching from short to continuous infusion format, these data also support our hypothesis. As 
predicted by the preclinical modeling, using a continuous infusion format allowed patients to 
achieve a higher total drug exposure. At MTD, continuous infusion resulted in an AUC of 1800 
mcg min/ mL[40] as compared to 590 mcg min/mL with the short infusion.[36] Unfortunately, 
comparative efficacy of the two formats could not be adequately assessed since the 
immunogenicity of SS1P prevented effective dosing over multiple cycles. Since multiple cycles 
of LMB-100 can be administered to most patients prior to the development of anti-drug antibodies, 
this provides an ideal opportunity to determine whether a continuous infusion format can improve 
therapeutic window in the clinic as predicted by pre-clinical models. 
Continuous LMB-100 will be delivered at a slow rate, i.e. which may be less than one mL per hour 
in some cases.  The FDA has issued a warning regarding such low infusion rates particularly 
pertaining to high risk or life-sustaining therapies.  However, LMB-100, is not considered to be a 
high risk (based on the fact that patients are currently tolerating infusions given over 30-60 
minutes) or life-sustaining therapy. 
1.2.8 Rationale for the initial dose and schedule and subsequent dose escalation of continuous 
infusion LMB-100 
Continuous infusion of 96 hours was deemed to be the optimal duration for infusion after taking 
into consideration feasibility of administration and the potential risk to participants from 


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28 
 
deconditioning while in hospital receiving continuous infusion of study drug, balanced against the 
possibility for increased efficacy with longer exposure times.  
As outlined in section 1.2.5 existing clinical PK data were used to generate a model that could 
simulate PK parameters during continuous infusion of LMB-100. This model predicts that 
continuous infusion of the same dose of LMB-100 over each 24 hours by continuous infusion as 
compared to daily bolus dosing would result in similar total LMB-100 exposure levels but much 
lower Cmax. Lower Cmax should result in decreased off-target toxicity (such as VLS), and our pre-
clinical data suggest this should not adversely affect efficacy. The effect of lower Cmax on on-target 
off-tumor toxicities (such as serosal membrane irritation) is not predictable, although increased 
on-target off-tumor toxicity was not apparent during clinical trial using a continuous infusion 
format of a predecessor mesothelin-targeted immunotoxin.[40]  
Taking potential risk for increased on-target off-tumor toxicity into consideration, a reduction in 
starting dose compared to short-infusion MTD will be used.  A dose of 65 mcg/ kg was chosen as 
the initial dose for the escalation because it had been a) previously tested in the short infusion 
format in the Roche study of single agent LMB-100, and b) would also result in participants 
receiving ~60% less drug per cycle compared to short infusion LMB-100 given at the MTD of 140 
mcg/kg every 48 hours for 3 doses (19.5 mg/ cycle versus 31.5 mg/cycle).  Based upon our 
simulations, we predict that participant drug exposure during a 96-hour continuous infusion of 65 
mcg/ kg/ day of LMB-100 will be 80% of that compared to patients who receive short-infusion 
LMB-100 given at MTD (5528 versus 6927 hr*ng/ml/ cycle).  Subsequent dose levels 
administering 100, 140 and 200 mcg/kg/day over 96 hour continuous infusion were included 
although simulated drug exposures will exceed that of the short infusion MTD because the 
unacceptable toxicities seen with short-infusion LMB-100 at dosages higher than the established 
MTD for this format (VLS and reversible acute kidney injury which prolonged hospitalization) are 
off-target toxicities, and likely to be minimized by the lower Cmax that is predicted with continuous 
infusion. 
Although 96 hours is considered the optimal duration for continuous infusion, initial dose levels 
will test continuous infusions of 65 mcg/kg/day of drug for shorter durations since simulated drug 
exposure over each 48 hours of continuous infusion at 65 mcg/kg/day is 20% higher than for the 
short infusion MTD (2764 versus 2309 hr*ng/mL/48hr).  This is because just one dose of LMB-
100 is given over 48 hours in the short infusion format.   
A loading dose of 40 mcg/kg LMB-100 given over 30-180 minutes will be administered prior to 
initiation of the continuous infusion beginning after Level 1. The loading dose is expected to 
improve efficacy by reducing tumor site barrier effect. Such affect has been observed in pre-
clinical studies and may impair access of LMB-100 to the tumor during continuous infusion. 
1.2.9 Rationale for use of mesothelin testing (NSR device) 
In order to be eligible for the Arm B1 lead in portion of the study, participants are required to have 
positive mesothelin expression in archival tumor tissue, defined as at least 25% of tumor cells 
expressing mesothelin. Mesothelin expression testing is not FDA approved for this purpose; 
however, it is being used as an in-vitro diagnostic device.  According to 21 CFR 812.3(m), a 
significant risk device presents a potential for serious risk to the health, safety and welfare of a 
subject and meets the significant risk criteria listed in the table below along with the sponsor’s 


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29 
 
conclusions with regard to the applicability of these criteria to the current study. The device has 
been assessed by the sponsor as non-significant risk per the below. 
 
Significant Risk Criteria 
Applicable to 
current study 
Justification 
Is an implant 
No 
The mesothelin test is not introduced into 
the subject 
Is used in supporting or 
sustaining human life 
No 
The device is diagnostic 
Is of substantial importance in 
diagnosing 
mitigating 
or 
treating disease or preventing 
impairment of human health 
No 
While the device is diagnostic, we do not 
believe in presents a potential for serious 
risk to the health and welfare of the subject. 
The assessment of mesothelin positivity is 
only used in tumors that may not have a 
high rate of mesothelin expression, and is 
assessed to help to increase the possibility 
that all persons enrolling on the study might 
derive benefit from therapy.  Persons that 
are deemed ineligible to enroll on the basis 
of this test are eligible for studies within 
TGMB that are not reliant on this test.   
Otherwise poses a risk 
No 
Testing will be performed on archival 
samples or on fresh tissue that is collected 
at screening for confirmation of diagnosis.  
No additional collection of tissue will occur 
for purposes of mesothelin testing. 
2 
ELIGIBILITY ASSESSMENT AND ENROLLMENT  
2.1 
ELIGIBILITY CRITERIA 
2.1.1 Inclusion Criteria 
2.1.1.1 For participants who will be receiving nab-paclitaxel (all arms except Arm B1 Single 
Agent Lead-in) 
2.1.1.1.1 Histologically confirmed recurrent, advanced or metastatic pancreatic ductal 
adenocarcinoma as determined by NCI Laboratory of Pathology. 
2.1.1.1.2 No treatment with paclitaxel or nab-paclitaxel within 4 months prior to initiation of 
study therapy 
2.1.1.1.3 ECOG performance status (PS) 01 (Appendix A). 


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2.1.1.1.4 Adequate hematological function: neutrophil count of t1.0 u109 cells/L, platelet count 
of t95,000/PL, hemoglobin ≥9 g/dL 
2.1.1.1.5 Measurable disease as per the RECIST Criteria v 1.1 (see section 6.3) 
2.1.1.2 For participants who will NOT receive nab-paclitaxel (Arm B1 Single Agent Lead-in 
only) 
2.1.1.2.1 Histologically confirmed solid tumor malignancy for which no curative therapy exists 
with at least 25% of tumor cells expressing mesothelin as determined by NCI 
Laboratory of Pathology. Determination can be made using archival tumor tissue or 
fresh biopsy. Subjects with epithelioid mesothelioma and pancreatic adenocarcinoma 
are automatically eligible and are not required to have this test 
2.1.1.2.2 ECOG performance status (PS) 02 (Appendix A). 
2.1.1.2.3 Adequate hematological function: neutrophil count of t1.0 u109 cells/L, platelet count 
of t85,000/Pl, hemoglobin ≥8.5 g/dL 
2.1.1.2.4 Measurable and/or evaluable disease as per the RECIST Criteria v 1.1 (see section 6.3) 
2.1.1.3 For all arms of the protocol 
2.1.1.3.1 Participants must have received at least one prior chemotherapy regimen for their 
disease. 
2.1.1.3.2 Age ≥18 years. Because no dosing or adverse event data are currently available on the 
use of LMB-100 alone or in combination with nab-paclitaxel in persons <18 years of 
age, children are excluded from this study.  
2.1.1.3.3 Participants must be more than 14 days removed from most recent minor surgical 
procedure (such as biliary stenting), 28 days from most recent major surgical procedure, 
14 days removed from most recent radiation therapy, chemotherapy or experimental 
drug treatment with published half-life known to be 72 hours or less and 28 days 
removed from last experimental drug treatment with unpublished or half-life greater 
than 72 hours. 
2.1.1.3.4 All acute toxic effects of any prior radiotherapy, chemotherapy, experimental drug 
treatment or surgical procedure must have resolved to Grade d1, except alopecia (any 
grade) and peripheral neuropathy. 
2.1.1.3.5 Serum albumin ≥ 2.5 mg/dL without intravenous supplementation 
2.1.1.3.6 Adequate liver function: Bilirubin, AST and ALT < 2.5 x ULN. AST and ALT up to 5x 
ULN is permitted for patients with liver metastases. 
2.1.1.3.7 Adequate renal function: creatinine clearance (by Cockcroft Gault formula Appendix B 
or measured) t50 mL/min. 
2.1.1.3.8 Must have left ventricular ejection fraction ≥ 50% 
2.1.1.3.9 Must have an ambulatory oxygen saturation of > 88% on room air 
2.1.1.3.10 The effects of LMB-100 alone or in combination with nab-paclitaxel on the developing 
human fetus are unknown.  For this reason, women of child-bearing potential and men 
must agree to use adequate contraception (hormonal or barrier method of birth control; 
abstinence) prior to study entry until 3 months the last dose of study therapy.  Should a 
woman become pregnant or suspect she is pregnant while she or her partner is 
participating in this study, she should inform her treating physician immediately. 


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2.1.1.3.11 Ability of participant to understand and the willingness to sign a written informed 
consent document. 
2.1.2 Exclusion Criteria 
2.1.2.1 Exclusion criteria for all study arms 
2.1.2.1.1 Known or clinically suspected CNS primary tumors or metastases including 
leptomeningeal metastases. History or clinical evidence of CNS metastases unless they 
have been previously treated, are asymptomatic, and have had no requirement for 
steroids or enzyme-inducing anticonvulsants in the last 14 days. 
2.1.2.1.2 Evidence of significant, uncontrolled concomitant diseases which could affect 
compliance with the protocol or interpretation of results, including significant 
pulmonary disease other than that related to the primary cancer, uncontrolled diabetes 
mellitus, and/or significant cardiovascular disease (such as New York Heart Association 
Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable 
arrhythmias, unstable angina, or clinically significant pericardial effusion)  
2.1.2.1.3 Any known diagnoses, metabolic dysfunction, physical examination finding, or clinical 
laboratory finding giving reasonable suspicion of a disease or condition (other than 
mesothelin [+] cancer diagnosis) that would contraindicate the use of an investigational 
drug, interfere with tumor measurement or lead to an expected life expectancy of less 
than 6 months as judged by the investigator 
2.1.2.1.4 Active or uncontrolled infections. 
2.1.2.1.5 Live attenuated vaccinations within 14 days prior to treatment 
2.1.2.1.6 Dementia or altered mental status that would prohibit informed consent 
2.1.2.1.7 Pregnant women are excluded from this study because the effects of LMB-100 on the 
developing fetus are unknown and may have the potential to cause teratogenic or 
abortifacient effects.  Because there is an unknown but potential risk for adverse events 
in nursing infants secondary to treatment of the mother with LMB-100, breastfeeding 
should be discontinued if the mother is treated with LMB-100.  These potential risks 
may also apply to other agents used in this study. 
2.1.2.1.8 Known hypersensitivity to any of the components of LMB-100 
2.1.2.1.9 Baseline QTcF interval of > 470 ms, participants with baseline resting bradycardia < 45 
beats per minute, or baseline resting tachycardia !100 beats per minute. 
2.1.2.2  Exclusion criteria specific to patients who will be receiving nab-paclitaxel (all arms 
except Arm B1 Single Agent Lead-in) 
2.1.2.2.1 Participants with contra-indication and/or history of severe hypersensitivity reactions to 
nab-paclitaxel  
2.1.2.2.2 Participants with baseline peripheral neuropathy greater than grade 2. 
2.1.2.2.3 HIV or active HBV or HCV infection due to risk of progression while receiving 
immunosuppressive chemotherapy 
2.2 
SCREENING EVALUATION 
Assessments will be performed any time prior to study enrollment. 


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32 
 
x Archival tumor sample for NCI LP confirmation of diagnosis.  A block of primary tissue 
(or 10 unstained sections on charged slides) from the time of diagnosis will be required 
from each participant.  Tissue blocks from a known recurrence will be accepted if original 
tumor samples are unavailable.  Referring institutions will send the tumor block or 10 
unstained sections on charged slides to CCR/NCI for correlative studies and confirmation 
of diagnosis.  A fresh biopsy may be collected if tumor tissue is not available. 
x For patients on the Arm B1 Single Agent Lead-in who do not have a diagnosis of 
epithelioid mesothelioma or pancreatic adenocarcinoma ONLY: archival tissue or fresh 
biopsy samples sufficient to assess tumor MSLN expression by immunohistochemistry 
analysis. 
Assessments performed within 28 days prior to study enrollment 
x History and physical exam 
x Vital signs including ambulatory oxygen saturation by pulse oximetry 
x ECOG performance status 
x Pregnancy test in women of childbearing potential 
x ECG 
x Echocardiogram 
x CT scan of chest, abdomen and/or pelvis and areas of known or suspected disease 
involvement; MRI may also be performed when appropriate 
x CBC with differential, Acute Care Panel (sodium, potassium, chloride, bicarbonate, 
creatinine, glucose, BUN), Hepatic Panel (alkaline phosphatase, AST, ALT, total bilirubin, 
direct bilirubin), Mineral Panel (albumin, calcium, magnesium, phosphorus), creatine 
kinase, C-reactive protein, CK, vitamin D, 1,25-dihydroxy, Coagulation (PT, PTT), lactate 
dehydrogenase 
x CA 19-9 serum tumor marker for pancreatic cancer patients (or other appropriate tumor 
marker for patients enrolled in Arm B1 Single Agent Lead-in who do not have pancreatic 
cancer) 
x Testing for HIV, HCV, HBV: anti-HIV antibody, Anti-HCV Antibody, HBs Ag Screening 
(except for Arm B1 Single Agent Lead-in) 
x Urinalysis 
2.3 
REGISTRATION PROCEDURES 
2.3.1 Arm B1, Single Agent Lead in Cohort Subjects with Diseases other than Epithelioid 
Mesothelioma or Pancreatic Adenocarcinoma Only 
Registration will be a two-part process as patients in this cohort that are not diagnosed with 
pancreatic adenocarcinoma or epithelioid mesothelioma are screened on this protocol. Authorized 
staff must register an eligible candidate with NCI Central Registration Office (CRO) within 24 
hours of signing consent. To initially register a subject after the participant has signed the consent, 
complete the top portion the registration Eligibility Checklist from the website 
(http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) indicating that the patient is being 
registered for screening and send via encrypted email to: NCI Central Registration Office 


Abbreviated Title: LMB-100 + Abrx in PDA 
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33 
 
ncicentralregistration-l@mail.nih.gov. Once eligibility is confirmed after completion of screening 
studies, complete the remainder of the form which is the eligibility checklist, indicating that the 
patient is being registered for treatment and email the completed registration checklist to the CRO 
at NCI Central Registration Office ncicentralregistration-l@mail.nih.gov. After confirmation of 
eligibility at Central Registration Office, CRO staff will call pharmacy to advise them of the 
acceptance of the patient on the protocol prior to the release of any investigational 
agents.  Verification of Registration will be forwarded electronically via e-mail to the research 
team. A recorder is available during non-working hours.  
Subjects that do not meet screening criteria should be removed from the study following the 
procedure in section 3.5.2.1. 
2.3.2 All other subjects 
Authorized staff must register an eligible candidate with NCI Central Registration Office (CRO) 
within 24 hours of signing consent.  A registration Eligibility Checklist from the web site 
(http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) must be completed and sent via 
encrypted email to:  NCI Central Registration Office ncicentralregistration-l@mail.nih.gov.  After 
confirmation of eligibility at Central Registration Office, CRO staff will call pharmacy to advise 
them of the acceptance of the participant on the protocol prior to the release of any investigational 
agents.  Verification of Registration will be forwarded electronically via e-mail to the research 
team. A recorder is available during non-working hours.  
2.3.3 Treatment Assignment  Procedures 
Cohorts 
Number 
Name 
Description 
A1 
Phase I Short Infusion 
Cohort 
The first 6 – 12 subjects with pancreatic cancer meeting nab-
paclitaxel eligibility criteria* to determine an MTD for part A. 
A2 
Phase II Short Infusion 
Cohort 
The next 14 – 20 subjects with pancreatic cancer meeting nab-
paclitaxel eligibility criteria* (until at least 13 subjects have 
been evaluated at the Part A MTD [stage 1]– a determination 
will then be made on whether to continue to 20 [stage 2]) 
B1 
Continuous Infusion, 
Single Agent Lead-In 
Cohort  
Up to 30 evaluable subjects with pancreatic cancer not meeting 
nab-paclitaxel eligibility criteria* or subjects with other 
mesothelin expressing tumors for part B MTD determination. 
B2 
Continuous Infusion, 
Combination Therapy 
Cohort 
Up to 6 subjects with pancreatic cancer meeting nab-paclitaxel 
eligibility criteria, followed by an additional 4 subjects if 
safety is established.  
* criteria specific for nab-paclitaxel are found in sections 2.1.1.1 and 2.1.2.2; criteria specific for 
subjects not receiving nab-paclitaxel are found in section 2.1.1.2 


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34 
 
Arms 
Number 
Name 
Description 
A1 
Phase I, Short infusion  
Subjects infused with escalating doses of LMB-100 on days 1, 
3 and 5 of each 21-day cycle.  Infusion length 30 – 180 
minutes.  Subjects will also receive nab-paclitaxel on day 1 of 
each cycle. 
A2 
Phase II, Short infusion  
Subjects infused at the LMB-100 dose determined in A1.  
Subjects will also receive nab-paclitaxel on day 1 of each 
cycle. 
B1 
Continuous Infusion, 
Single Agent Lead-In  
Subjects infused with LMB-100 monotherapy at escalating 
doses or escalating durations once per cycle– duration may 
range from 24 – 96 hours 
B2 
Continuous Infusion, 
Combination Therapy 
Subjects infused with LMB-100 at the dose level/dose 
duration determined after B1 is complete.  Subjects will also 
receive nab-paclitaxel on day 1 of each 14-day cycle. 
Arm Assignment 
Subjects will be directly assigned to each arm as follows: 
x Subjects in Cohort A1 will be directly assigned to Arm A1. 
x Subjects in Cohort A2 will be directly assigned to Arm A2 once an MTD has been 
determined in Arm A1.  Accrual to stage 2 of Arm A2 may commence after stage 1 is 
completed, but priority will be given to Arms B1 and B2. Note: Cohort/Arm A2 will not 
be opened if dose level -1 is not deemed safe in part Cohort/Arm A1. 
x Subjects in Cohort B1 will be enrolled concurrently with subjects in Arm A1 & Arm A2 
(if this arm is opened) and will be directly assigned to Arm B1.  Priority will be given to 
Arm A1 followed by B1 then A2. 
x Subjects in Cohort B2 will be enrolled after Cohort/Arm B1.  These subjects are directly 
assigned to Arm B2. Enrollment to Arm B2 will be given priority over Arm A2 if these 
arms enroll concurrently.  
3 
STUDY IMPLEMENTATION 
3.1 
STUDY DESIGN 
This is a first-in-human, open-label, Phase I/II study of LMB-100. It will be conducted in four 
parts. Three of the four parts accrue the same population of patients with advanced pancreatic 
cancer (indicated by black outline around the arrows in the schema below): 
 
 


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35 
 
 
 
x Arm A1 (Phase I study): Dose escalation of short infusion LMB-100 with fixed dose nab-
paclitaxel in patients with advanced pancreatic cancer 
x Arm B1 Single Agent Lead-in: Dose escalation of continuous infusion LMB-100 as a 
single agent in patients with any solid tumor malignancy expressing MSLN. This part will 
run concurrently with Arm A1 since it accrues a different patient population. 
x Arm B2: Single dose level of continuous infusion LMB-100 with fixed dose nab-paclitaxel 
in patients with advanced pancreatic cancer. This part can begin accrual after completion 
of Arm B1 Single Agent Lead-in. 
x Arm A2 (Phase II study): Investigates the clinical activity at MTD and/or RP2D for short 
infusion combination therapy with nab-paclitaxel in a 2-stage design.  The arm may not be 
explored if dose level -1 is deemed to be unsafe in Arm A1. If Arm A2 is opened, stage 2 
will only be accrued if pre-specified response criteria for Stage 1 are met.  Priority will be 
given to accrual of Arm B2 (which requires the same patient population) over either stage 
of Arm 2.  
* Eligibility requirements allow for accrual of patients with any solid tumor malignancy that 
expresses MSLN. Participants in this arm will NOT receive nab-paclitaxel 
3.1.1 Study Schema for short infusion LMB-100 with nab-paclitaxel (Arm A1 (Phase I)) 
 
 
 
Cycles 1–2 
(21 days) 


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36 
 
Participants will be treated with short infusion LMB-100 in combination with nab-paclitaxel for 2 
cycles or until unacceptable toxicities, disease progression (per PI discretion), withdrawal from 
treatment for other reasons, or death, whichever occurs first.  During the phase I portion of the 
study, participants who withdraw prior to completing the DLT assessment period (for any reason 
other than toxicity) will be replaced.  
Arm A1 (Phase I) will utilize a dose escalation with LMB-100 administered in combination with 
a fixed dose of nab-paclitaxel (IV, 125 mg/m2). All cycles will be 21-days.  Nab-paclitaxel will be 
administered on days 1 and 8.  Participants will receive LMB-100 IV over 30 -180 minutes on 
Days 1, 3 and 5 (QOD x3). 
 
3.1.2 Study Schema for continuous infusion LMB-100 (Arm B1 [Single Agent Lead-in]) 
 
Participants will be treated with LMB-100 by continuous infusion over 24 - 96 hours with or 
without a loading dose depending on dose level for 2 cycles or until unacceptable toxicities, disease 
progression (per PI discretion), withdrawal from treatment for other reasons, or death, whichever 
occurs first.  During the phase I portion of the study, participants who withdraw prior to completing 
the DLT assessment period, for any reason other than toxicity, will be replaced. 
This arm will utilize a dose escalation of LMB-100.  All cycles will be 21-days.  Participants will 
receive continuous infusion of LMB-100 IV for the 1, 2, 3 or 4 days of each cycle depending on 
dose level. 
 
3.1.3 Study Schema for continuous infusion LMB-100 with nab-paclitaxel (Arm B2) 
 


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37 
 
Up to 6 evaluable participants will be treated with LMB-100 by continuous infusion over 24  hours 
with a loading dose in combination with nab-paclitaxel for 3 cycles of 14 days duration or until 
unacceptable toxicities, disease progression (per PI discretion), withdrawal from treatment for 
other reasons, or death, whichever occurs first.  The DLT period will include the first 28 days 
following initial infusion of LMB-100 on C1D1. Participants who withdraw prior to completing 
the DLT assessment period, for any reason other than toxicity, will be replaced. Participants may 
be enrolled concurrently. If no more than 2 of the 6 evaluable subjects experience unacceptable 
toxicity (as defined by DLT criteria in section 3.1.5), up to 4 additional participants may be accrued 
concurrently to better assess the safety and activity of this regimen. 
This arm will utilize a single dose of LMB-100 in combination with a fixed dose of nab-paclitaxel 
(IV, 125 mg/m2).  All cycles will be 14 days.  Nab-paclitaxel will be administered on Day 1 . 
Participants will receive a 24-hour infusion of LMB-100 IV on Day 1 of each cycle for a total of 
3 cycles. 
3.1.4 Study Schema for Phase II 
Participants enrolled on the Phase II portion of the trial will be treated using the same schedule of 
short infusion LMB-100 and nab-paclitaxel as given for Arm A1 (See Section 3.1.1), at the 65 
mcg/kg  dose of LMB-100, the RP2D in Part A. They will be treated for 2 cycles or until 
unacceptable toxicities, disease progression (per PI discretion), withdrawal from treatment for 
other reasons, or death, whichever occurs first. During the phase II portion of the study, 
participants who are not evaluable for response assessment will be replaced. 
The phase II study (Arm A2) will be conducted in a Simon Minimax two stage phase II design.  
The first stage will enroll 13 evaluable participants, including the six participants treated at 65 
mcg/kg. If 1 or more has a response, then accrual would continue until a total of 20 evaluable 
participants have been enrolled. 
3.1.5 Dose Limiting Toxicity 
The DLT period for Arm A1, A2 and B1 will consist of the 21 days following first administration 
of LMB-100 (1 cycle), while that for Arm B2 will include 28 days following first administration 
of LMB-100 (2 cycles). For the purpose of this study, a DLT will be defined as any of the following 
events attributed to LMB-100 (i.e. related to LMB-100) and occurring during the DLT period: 
Hematological toxicities: 
x 
Grade 4 neutropenia (i.e. absolute neutrophil count (ANC) <0.5 x 109 cells/L) for a 
minimum duration of 7 days) 
x 
Grade 3 and 4 febrile neutropenia (i.e. ANC < 1.0 x109 cells/L with a single 
temperature of >38.3°C or a sustained temperature of ≥38°C for more than one hour 
x 
Grade 4 thrombocytopenia (≤25.0 x109 cells/L) 
x 
Grade 3 thrombocytopenia associated with bleeding episodes 
Grade ≥3 non-hematological toxicity with the exception of: 
x 
Grade 3 nausea and vomiting without appropriate treatment 
x 
Grade 3 diarrhea lasting for ≤2 days with no fever or dehydration 
x 
Grade 3 infusion-related reactions are not considered to be DLTs since, based on 


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38 
 
experience with monoclonal antibodies, IRRs are idiosyncratic and not dose-related 
events.  
x 
Asymptomatic grade 3 elevation of ALT, AST, GGT, bilirubin or alkaline 
phosphatase attributable to study drug that persists for less than 7 days.  (Please 
note that all grade 4 elevations in these parameters should be considered a DLT) 
x 
Asymptomatic laboratory values (other than ALT, AST, GGT, bilirubin, 
alkaline phosphatase or creatinine) of Grade 3 that are judged not clinically 
significant by the investigator.  
x 
Isolated Grade 3 fever (without signs and/or symptoms of an infection) 
occurring within 48 hours of LMB-100 infusion and resolving within 48 hours 
to ≤ Grade 2 and fully resolved within 1 week 
Grade ≥ 4 non-hematological toxicity: 
x 
Infusion-related reactions 
Other toxicities: 
x 
Any other drug related toxicity considered significant enough to be qualified as a 
DLT in the opinion of the principal investigator. 
If a participant experiences a DLT of any grade, the investigator will have the option to either stop 
the LMB-100 treatment or to resume the treatment at the next lowest dose level of LMB-100 based 
on best clinical judgment. This can be done to allow participants, who could potentially benefit 
from LMB-100, to remain on the study drug treatment, if considered the most beneficial therapeutic 
option for the participant while managing and monitoring the participant’s safety risks. 
3.1.6 Dose Escalation 
Dose escalation will proceed in cohorts of 3–6 participants. The MTD is the dose level at which 
no more than 1 of up to 6 participants experience DLT during cycle 1, and the dose below that at 
which at least 2 (of ≤6) participants have DLT from the study drug. If a participant did not 
experience DLT and did not finish treatment, he or she will not be evaluable for toxicity and will 
be replaced in the dose level to ensure that at least 3 participants in each cohort have been assessed 
for the full DLT period prior to moving to the next dose level. If 2 or more DLTs occur at dose 
level 1, dose level -1 will be evaluated. 
3.1.6.1 Dose escalation tables. 
3.1.6.1.1 Arm A1 (Phase 1 short infusion) 
Dose Escalation Schedule Arm A1 (Phase I) 
Dose Level 
Dose of LMB-100 in μg/kg  
Level -1 
65  
Level 1 
100 
Level 2 
140 


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39 
 
 
3.1.6.1.2 Arm B1 (Single Agent Lead-in Continuous Infusion) 
Table 9 
Dose/ Duration Escalation Scheme 
  
LMB-100 
(mcg/kg/day) 
Schedule 
Level 1 
65 
48h 
Level 2 
100 
48h 
Level 3 
100 
24h, D1 & 4 
Level 3R 
100 
24 h, D1 only 
Level 4 
140 
24 h, D1 &4 
R(educed) - As the occurrence of more than 1 DLT will not 
automatically trigger a return to a previously attempted dose 
level, dose levels with an R designation will be identified for 
exploration as the study proceeds should more than 1 DLT 
occur in a previously named dose level 
Table 10 
Dose Steps 
LMB-100 
(mcg/kg/day) 
I 
65 
II 
100 
III 
140 
IV 
200 
Table 11 
Duration 
Steps 
Infusion Duration 
(hrs) 
A 
24 
B 
24, D1 & D4 
C 
48 
D 
72 
E 
96 
 
For Arm B1 (Single Agent Lead-in), the initial dose for Level 1 was defined at 65 mcg/kg/day 
over 48 hours and was completed after accrual of 3 participants (2 of whom were evaluable for 


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40 
 
DLT). No safety or efficacy signal was observed at this dose level. Based on these results, Dose 
Step I (65 mcg/kg/d) may no longer be used, such that the minimum Dose Step after Dose Level 
1 is Dose Step II (100 mcg/kg/d).  Beginning with Level 2, participants will receive short infusion 
of 40 mcg/kg LMB-100 over the first 30-180 minutes followed by the continuous infusion defined 
in Table 9.  DLT was observed in 1/6 patients at Level 2, and testing proceeded to Level 3, a 
planned dose de-escalation. After accruing 6 patients to dose level 3, 3 of which were evaluable 
for toxicity due to hold of day 4 dose for toxicity unrelated to study drug, it was determined by the 
investigator to close this arm of the and begin accrual to Arm B2. 
If a Level is determined to be unsafe as defined in section 3.1.6.1.3, then: a) the preceding Level 
may be declared the MTD, or b) additional Levels may be tested so long as either the dose or the 
duration of infusion is stepped down) to a lower level that has not been previously tested as pre-
defined in Table 10 and Table 11.  Such doses carry the R designation for reduced in Table 9. For 
this arm of the study, there is no pre-defined number of dose levels.  Dose tuning may continue 
until both the maximum drug dose and duration of infusion are defined or a maximum of 30 
participants are treated on this arm. As dose tuning progresses, slots must be reserved in a manner 
that insures at least 6 participants can be treated at the RP2D. 
For Arm B2, a single dose of LMB-100 has been chosen based upon safety and tolerability seen 
with single agent LMB-100 given in continuous infusion format in Arm B1 and taking into 
consideration safety and tolerability seen in Arm A1 with the combination. Given the low 
incidence of VLS causing weight gain greater than 5 kg with 24-hour continuous infusion given 
on Day 1 and that 48-hour continuous infusion given on Day 1 is the MTD for long infusion, the 
following LMB-100 dose will be tested in combination with standard nab-paclitaxel (125 mg/m2): 
x 40 mcg/kg IV loading dose of LMB-100 given over 30 minutes (to follow nab-paclitaxel 
administration by 30 minutes ±20 minutes) on Day 1 
x 100 mcg/kg LMB-100 IV given over 24 hours to immediately following loading dose 
These drugs will be given on a 14-day cycle to improve tolerability, rather than giving nab-
paclitaxel on Days 1 and 8 as in Part A. 
 


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3.1.6.1.3 Dose finding will follow the rules outlined in the Table below. 
Number of Participants 
with DLT 
at a Given Dose Level 
Escalation /De-Escalation Decision Rule 
0 out of 3 
Enter up to 3 participants at the next (integer) dose 
level OR may treat 1-3 additional participants to better 
define safety signal. 
> 2 
Per the discretion of the investigator, dose escalation 
may be stopped.  This dose level will be declared the 
maximally 
administered 
dose 
(highest 
dose 
administered).  Up to three (3) additional participants 
will be entered at the next lowest previously explored 
dose level that resulted in fewer than 2 DLTs if only 3 
participants were treated previously at that dose. 
OR 
Enter up to 3 participants at the next dose level (R 
designation) meeting criteria of not previously 
explored and at either lower dose or lower infusion 
duration  
1 out of 3 
Enter up to 3 more participants at this dose level. 
x If 0 of these 3 participants experience DLT, 
proceed to the next integer dose level. 
x If 1 or more of this group suffer DLT, then: 
o dose escalation may be stopped per PI 
discretion, and this dose is declared the 
maximally administered dose.  UP to three (3) 
additional participants will be entered at the 
next lowest dose level that resulted in fewer 
than 2 DLTs if only 3 participants were 
treated previously at that dose. 
OR 
o Enter up to 3 participants at the next dose level 
(R designation) meeting criteria of not 
previously explored and at either lower dose 
or lower duration 
<1 out of 6 at highest dose 
level below the maximally 
administered dose 
This is the MTD.   
 


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3.2 
DRUG ADMINISTRATION 
Standard templates for a Chemotherapy Note for a patient on this study are available in Appendix 
C. 
3.2.1 LMB-100 
The qualified health care professional responsible for dispensing the study drug will prepare the 
correct dose according to the cohort or group allocation of each participant.  
Short infusion LMB-100 will be given as an IV solution on Days 1, 3 and 5 (QOD x3) of a 21-day 
cycle. Infusion duration should be 30-180 minutes. Continuous infusion LMB-100 will be given 
as an IV solution by syringe driver pump 1, 2, 3 or 4 days of a 21-day cycle depending on dose 
level. For continuous infusion Levels 2 and above, a loading dose of 40 mcg/kg LMB-100 given 
as an IV solution over 30-180 minutes will precede the start of continuous infusion on Day 1 and 
if applicable, Day 4.   
LMB-100 must be administered in a hospital or clinic equipped for IV chemotherapy. Full 
emergency resuscitation facilities should be immediately available and participants should be 
under close supervision of the investigator or delegate at all times.  
The compatibility and stability of the active ingredient was tested under simulated 
preparation/administration conditions. 
3.2.1.1 General Instructions 
1. LMB-100 drug product should be inspected visually for particulates prior to 
administration. 
2. LMB-100 is to be handled following all hazardous precautions. 
3. Do not use the solution if there is particulate matter or if it is discolored. 
4. Do not shake or freeze the vial contents. 
5. Ensure the drug vial content is protected from light during preparation and administration 
(ambient light conditions are acceptable but avoid exposure to direct sunlight). 
6. LMB-100 drug product does not contain any preservatives. Vials are for single use only 
and partially used vials must not be reused.   
7. Any unused product should be kept for drug reconciliation. 
8. No dilution of LMB-100 drug product into 0.9% saline bags should be performed. 
9. Do not administer as IV push or bolus. 
10. Other drugs that require parenteral co-administration (if applicable) should be delivered 
via separate infusion lines and at separate infusion sites and should not be mixed with the 
study drug. 
3.2.1.2 Specific Instructions  
LMB-100 is diluted with 0.9% NaCl in-line immediately prior to administration (see Figure 8 
below).  


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The undiluted LMB-100 drug product (DP), filled in a disposable syringe, is administered by 
intravenous syringe infusion using a syringe driver pump. So as not to compromise drug product 
physico-chemical stability, the dilution with 0.9% NaCl should be done in line, immediately prior 
to administration of the neat DP. 
In order to allow in-line dilution (1:10) immediately prior to administration of neat drug product, 
a side flow with 0.9% NaCl must be applied (as illustrated in Figure 8).  The side flow should be 
set-up at 1:10 in order to deliver 0.1 mg/mL DP. During continuous infusion, the minimum rate 
for 0.9% NaCl infusion should be 20 mL/ hour (to prevent line occlusion), even if this results in a 
less concentrated infusion of study drug. An IV infusion pump and syringe driver should be used 
to control the infusion rate of isotonic 0.9% NaCl solution and LMB-100 respectively.   
LMB-100 must be administered using a central venous catheter or an existing mediport for 
infusions lasting longer than 150 minutes. Central line access is neither required nor anticipated 
for patients in the short-infusion cohorts; however, a central line or use of an existing mediport 
may be permitted per PI discretion.  For continuous infusion, syringes should be switched out 
every 12 hours (± 1 hour), which will require 2 syringes per 24 hour infusion, 4 syringes per 48 
hour infusion, 6 syringes per 72 hour infusion and 8 syringes per 96 hour infusion.  
 
 
 
Figure 8:  
Schematic view of the administration set-up. 
The stopcock will be changed every 24 hours to prevent microbial ingress.  In line 
filters for the LMB-100 drug product as well as the saline will be used as depicted.   
1. The syringes for administration must be prepared under appropriate aseptic conditions as 
LMB-100 drug product does not contain antimicrobial preservatives. All preparation 


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should be conducted under laminar flow hood with safety glasses, lab coat and arm 
protection and a work procedure to minimize particle contamination.  
2. An in-line filter will be used to filter the undiluted drug product (LMB-100) during syringe 
infusion before side-flow dilution. For this, an in-line filter (0.2 or 0.22 μm pore size) 
should be positioned between the syringe extension line and the injection/infusion valve 
(see Figure 8). The filtration must occur before in-line dilution with 0.9% saline. 
An in-line filter will be used during saline infusion as shown in Figure 8.   
3. Withdraw up to 3 ml excess volume of LMB-100 to the intended dosing volume into the 
syringe for priming and purging the syringe extension lines before administration (see step 
9).   
4. The prepared syringe should be stored and transported with a closing cone/stopper. 
5. Since LMB-100 drug product does not contain antimicrobial preservatives and to comply 
with the chemical and physical in-use stability, the prepared syringes for infusion should 
be used immediately. If not used immediately, total storage times of prepared syringes 
should not exceed 12 hours to limit microbial growth in case of potential accidental 
contamination.  Storage conditions should generally be at 2°C to 8°C, but syringes may be 
held at room temperature for up to a maximum of 4 hours.  The temperature during syringe 
preparation, storage and drug administration must not exceed 25 °C. 
6. A freshly prepared syringe of drug product is required for every 12 hours of LMB-100 
infusion and for the loading dose. To limit the potential for microbial growth, when 
preparing syringes for continuous infusion, drug vials may not be stored and reused to 
prepare syringes at later time points.  The syringe for the loading dose and that for the 
initial 12 hours of continuous infusion may be prepared from the same vial.  All other 
syringes must be prepared from a fresh vial. Saline bags must be changed at least every 24 
hours. 
7. Continuous infusion may be stopped for a total of up to 90 minutes within each 24 hour 
period for logistical purposed.  All stoppages should be documented in CRIS (both actual 
or estimated stop time and actual restart time) 
8. Establish the saline flow first by flushing the lines including the 4-way stopcock and 
extension lines with saline.  
9. Put the filled syringe in the pre-programmed syringe driver, remove the cap and attach the 
infusion set. Follow the syringe driver manual/local instructions regarding how to set up 
and prime/purge the system before the line is attached to the closed 4-way stopcock before 
starting the administration. 
10. The end of infusion is defined as the time point at which the syringe driver finishes 
administering the total volume of IMP to be infused.  
11. In case of any adverse events related to the infusion, please refer to the specific 
recommendation described in section 3.3.1.  
12. The line for drawing blood for PK samples should be placed in the opposite extremity from 
the one with the infusion line. 


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3.2.1.3 Monitoring 
3.2.1.3.1 Short Infusion 
During short infusion, vital signs (including, if possible, supine diastolic and systolic blood 
pressure, pulse rate, and temperature) must be monitored pre-infusion, every 15 minutes (± 5 
minutes) until the end of the infusion, and thereafter, every 30 minutes (±10 minutes) for 2 hours 
after the end of the first infusion. For subsequent infusions, if no IRR has been reported, monitoring 
will continue for 30 minutes after the end of the infusion. Vital signs during the infusion are not 
required to be captured in the eCRF unless abnormalities are observed. 
3.2.1.3.2 Continuous Infusion 
During continuous infusion, vital signs including, if possible, supine diastolic and systolic blood 
pressure, pulse rate, and temperature) must be monitored pre-infusion, every 15 minutes (± 5 
minutes) for the first two hours of the infusion, and thereafter, every 60 minutes (±10 minutes) for 
the next 4 hours of the infusion, and then every 6 hours until the infusion is completed. Vital signs 
should also be recorded 2 hours (±10 minutes) after the end of infusion. 
3.2.1.4 Standard Pre-medication for Participants Receiving LMB-100 
Due to the prevalence of infusion related reactions (IRRs) seen in the previous study of LMB-100, 
all patients will be pre-medicated 30-60 minutes (+30 minutes) prior to each LMB-100 
administration with the following medications: 
o Diphenhydramine 25-50 mg PO or IV 
o Ranitidine 150 mg PO 
o Acetaminophen 650 mg PO 
Dexamethasone 8 mg IV should be physically available in the infusion unit in case of severe IRR 
during LMB-100 administration.   
3.2.1.4.1 Additional Precautions at subsequent Infusions of LMB-100 in patients with prior IRR 
during short infusion of LMB-100 
Participants receiving short infusion having experienced an IRR of Grade 2 to 4 on a previous 
infusion despite standard pre-mediation should also receive: 
o Dexamethasone 20 mg, PO, 6-12 hours prior to LMB-100 administration, OR 
o Dexamethasone 8 mg, IV, 30 – 60 minutes (+30 minutes) prior to LMB-100 
administration, OR 
o equivalent dose of another corticosteroid as clinically indicated 
(See section 3.3.1 for complete instructions on response to IRRs) 
Participants who experienced an IRR of Grade 3 or 4 on a previous infusion where dexamethasone 
or another steroid was pre-administered should not receive further LMB-100 and will be 
discontinued from study therapy 
 
3.2.1.4.2 Additional Precautions for administration of LMB-100 in patients with IRR during 
continuous infusion of LMB-10 


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Participants receiving continuous LMB-100 infusion having experienced an IRR of Grade 2 to 4 
earlier in the current infusion or during a previous infusion despite standard pre-mediation should 
receive for the remainder of the infusion and all subsequent infusions accompanied by: 
o Diphenhydramine 25-50 mg PO or IV, q6 hours 
o Ranitidine 150 mg PO, q12 hours 
o Acetaminophen 650 mg PO, q12 hours 
o Dexamethasone as described earlier in this section, q12 hours 
(See section 3.3.1 for complete instructions on response to IRRs) 
Participants who experienced an IRR of Grade 3 or 4 where dexamethasone or another steroid was 
pre-administered within the last 12 hours should not receive further LMB-100 and will be 
discontinued from study therapy. 
Table 12 - Premedications for LMB-100 
Dose (mg) 
Route 
Acetaminophen 
650 
PO 
Diphenhydramine 
25-50 
PO or IV 
Ranitidine 
150 
PO 
Dexamethasone PRN 
8 
OR 
IV 
Dexamethasone PRN 
20 
PO 
3.2.2 Nab-Paclitaxel  
Nab-paclitaxel will be administered according to the package inserts at a dose of 125 mg/m2, 
intravenously over 30 minutes ± 10 minutes on Days 1 and 8 of each 21-day cycle. Detailed 
information about the preparation of the infusion solution and administration of nab-paclitaxel 
including information about compatible infusion bags, administration sets, and in line filters can be 
found in the package insert. 
3.2.3 Co-administration of Nab-paclitaxel and LMB-100 
On days when both LMB-100 and nab-paclitaxel are both scheduled to be administered (Day 1 of 
each cycle), nab-paclitaxel will be administered first.  LMB-100 infusion will be initiated 30 
minutes ± 20 minutes after completion of the nab-paclitaxel.  
3.3 
DOSE MODIFICATIONS 
Potential overlapping toxicities of LMB-100 and nab-paclitaxel must be considered. In this 
context, peripheral edema (10%) and arthralgia (11-13%) have been seen with both drugs.  Nab-
paclitaxel has been shown to cause life-threatening pneumonitis in a small percentage of patients. 


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Symptomatology of pneumonitis related to nab-paclitaxel could overlap with pleuritis, which is an 
identified toxicity risk with LMB-100. Study participants will be carefully monitored for adverse 
events associated with these organ systems. 
3.3.1 LMB-100 
Table 13 below provides a guideline on how to manage certain toxicities which are expected with 
LMB-100 based on preclinical studies and previous clinical experience with LMB-100 and 
molecules in the same class. 
Table 13 - Guidelines for Managing Specific LMB-100 Adverse Events 
Event 
Action to Be Taken 
IRR/hypersensitivity reaction during 
short infusion of LMB-100 
(Arms A1 and A2) 
If an IRR/hypersensitivity develops, the infusion of LMB-100 
should be temporarily interrupted. The participant should be 
monitored until complete resolution of the symptoms and treated 
as clinically indicated. Treatment or concomitant medication 
may include IV saline, oxygen, bronchodilators, corticosteroids, 
and vasopressors depending on the symptoms. 
If the short infusion is interrupted (Arms A1 or A2): 
o 
In the event of IRR CTCAE Grade1, upon resolution of 
symptoms, the infusion will resume at the same rate (the 
rate being used at the time that the IRR occurred). 
o 
In the event of IRR Grade 2 or 3, upon resolution of 
symptoms, the infusion will resume at one-half the 
previous rate. The infusion can be re-escalated to initial rate 
if considered well tolerated after 1 hour of infusion. 
o 
In the event of IRR CTCAE Grade 3, or CTCAE Grade 4 
(which may include pulmonary or cardiac events) or an 
anaphylactic reaction: 
 The infusion must be stopped and the participant should 
receive aggressive treatment 
 Participants experiencing IRR CTCAE Grade 4 or 
anaphylaxis must be permanently discontinued from 
study treatment 
For participants receiving short infusion LMB-100 who 
previously experienced IRR CTCAE tGrade 2, the infusion rate 
for subsequent LMB-100 infusion should be reduced to one-half 
of the previous rate and corticosteroids premedication should be 
given 30 minutes prior to infusion in addition to standard pre-
medications: 
o 
Dexamethasone (20 mg PO 6 -12hrs before infusion or 8 
mg IV, 30 - 60 min [+ 30 minutes] before infusion) or 
equivalent dose of another corticosteroid as clinically 
indicated 


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Event 
Action to Be Taken 
IRR/hypersensitivity reaction during 
continuous infusion of LMB-100 
(Arms B1 and B2) 
If an IRR/hypersensitivity develops, the infusion of LMB-100 
should be temporarily interrupted. The participant should be 
monitored until complete resolution of the symptoms and treated 
as clinically indicated. Treatment or concomitant medication 
may include IV saline, oxygen, bronchodilators, corticosteroids, 
and vasopressors depending on the symptoms. 
In the event of IRR CTCAE Grade 4 (which may include 
pulmonary or cardiac events) or an anaphylactic reaction: 
 The participant should receive aggressive treatment 
 Participants experiencing IRR CTCAE Grade 4 or 
anaphylaxis must be permanently discontinued from 
study treatment 
In the event of IRR CTCAE Grade 1, 2, 3, upon resolution of 
symptoms, 
o 
If the loading dose is interrupted, the remainder of the 
loading dose should be omitted and the patient should 
resume with the continuous infusion. 
o 
If the continuous infusion is interrupted: 
 Patients should be retreated with the standard pre-
medications if the infusion has already proceeded for 6 
hours or more 
 The infusion will resume at the same rate 
 Patients should receive repeated dosing of the standard 
pre-medications and dexamethasone at the intervals 
specified in Section 3.2.1.4.2 
Participants receiving continuous infusion LMB-100 who have 
experienced IRR CTCAE tGrade 2  infusion, should receive: 
o 
Standard pre-medications 30-60 minutes prior to start of 
infusion 
o 
Standard corticosteroids premedication should be given 30 
minutes prior to subsequent infusion in addition to standard 
pre-medications: 
 Dexamethasone (20 mg PO 6 -12hrs before infusion or 8 
mg IV, 30 - 60 min [+ 30 minutes] before infusion) or 
equivalent dose of another corticosteroid as clinically 
indicated 
o 
Repeated dosing of standard pre-medications and 
dexamethasone at the following intervals: 
 Dexamethasone, q12 hours  
 Diphenhydramine, q6 hours 
 Acetaminophen, q12 hours 


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Event 
Action to Be Taken 
 Ranitidine, q12 hours 
Vascular leak syndrome 
In the event of Grade ≥2 CTCAE vascular leak syndrome 
(medical intervention indicated): 
o 
Vasopressor support (e.g., phenylephrine) if indicated to 
stabilize blood pressure 
o 
Administer colloidal solutions (e.g., albumin) if there is a 
clinically significant, symptomatic and persistent systolic 
blood pressure drop, urine output significantly declines or 
serum albumin falls to 2.5 mg/dL or lower 
o 
For pulmonary congestion provide diuretic and/or albumin 
treatment as appropriate 
o 
Progressive shortness of breath may require endotracheal 
intubation or drainage of a pleural effusion 
o 
For oliguria and /or rising serum creatinine level delay 
LMB-100 if Grade 3 urine output (<10 mL/hr) 
o 
Use dopamine if participant is unresponsive to or unable to 
tolerate fluids.  
o 
In the event of Grade ≥2 CTCAE pericardial effusion 
(asymptomatic effusion small to moderate size), consider 
delaying LMB-100 administration. In the event of Grade 
≥3 CTCAE pericardial effusion (effusion with physiologic 
consequences) stop LMB-100 treatment until full 
resolution 
Inflammatory reactions to serosal 
membranes  
o 
Hydrocortisone (200 mg IV) or equivalent dose of another 
corticosteroid as clinically indicated 
o 
In the event of Grade 2 CTCAE pericardial effusion 
(asymptomatic effusion small to moderate size), consider 
delaying LMB-100 administration. In the event of Grade 
≥3 CTCAE pericardial effusion (effusion with physiologic 
consequences) stop LMB-100 treatment until full 
resolution 
o 
In the event of pleuritis resulting in mild to severe pleuritic 
pain, treat with analgesics or steroids as clinically indicated 
o 
For participants who have previously experienced pleuritis 
consider administration of dexamethasone 4 mg, PO bid 
beginning with first LMB-100 infusion and completing 24 
hours after the last LMB-100 infusion of the cycle. (If 
participant is already receiving corticosteroids at dose and 
schedule at or above this amount as part of the pre-
medication regimen, do not give additional steroids for 
pleuritis) 
Dehydration 
Encourage that participants maintain oral hydration (~1.5 L/ day) 


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Event 
Action to Be Taken 
Nausea 
Ondansetron or another anti-emetic should be available as needed 
during Days 1-6 of each cycle 
Renal toxicity 
In the event of Grade 1 or greater renal toxicity consider 
increasing oral or intravenous hydration, consider delaying 
LMB-100 administration by up to 48hrs. 
In the event of Grade 2 or great renal toxicity hold LMB-100 
administration until recovery to Grade 1 or better.  If this does 
not occur within 48hrs, no further LMB-100 should be given 
during the cycle.  
IRR = infusion related reaction; IV = intravenous; CTCAE = Common Terminology Criteria for Adverse 
Events 
3.3.2 Nab-paclitaxel 
If nab-paclitaxel is withdrawn prior to completion of treatment, LMB-100 may still be continued 
in the absence of progressive disease. 
3.3.2.1 Dose levels 
Dose modifications of nab-paclitaxel for myelosuppression and other chemotherapy related 
toxicities will be made as per package insert. 
 


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3.4 
STUDY CALENDARS 
3.4.1 Calendar for patient receiving short infusion LMB-100 (Arms A1 and A2) 
1 cycle = 21-days,  
Unless otherwise indicated, screening assessments must occur within 28 days prior to enrollment.  Cycle 1, day 1 assessments with the exception of 
imaging studies may occur up to 3 days prior to treatment initiation. Imaging studies must be completed ± 7 days from the indicated time. If screening 
assessments are performed within the appropriate timeframe for Cycle 1 Day 1 assessments, they do not need to be repeated on that day. 
Beyond cycle 1, performance status and standard laboratory assessments may be performed up to 1 day prior to the indicated time. 
Dosing cycles after cycle 1 may be delayed for up to one week to accommodate schedule conflicts, Federal holidays and inclement weather, etc. 
They may be delayed for up to two weeks due to toxicity. 
Cycle 1 -2 
Post Therapy 
Procedure 
Screening 
Day 1 
Day 3 
Day 5 
Day 8 
Withdrawal 
visit5 
Safety Follow 
Up Visit6 
Long Term 
Follow Up 
Nab-paclitaxel 
 
X 
 
 
X 
 
 
 
LMB-100 
 
X 
X 
X 
 
 
 
 
History and PE 
X 
X 
 
 
 
X 
X 
 
Weight 
 
X 
X 
X 
X 
X 
X 
 
Height 
 
X 
 
 
 
 
 
 
Vital signs1 
X 
X 
X 
X 
X 
X 
X 
 
PS 
X 
X 
 
 
 
X 
 
 
Labs2 
X 
X 
X 
X 
X 
X 
X 
 
1,25-dihydroxy Vit D 
X 
 
 
 
 
X 
 
 
Hepatitis and HIV screening panel 
X 
 
 


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Cycle 1 -2 
Post Therapy 
Procedure 
Screening 
Day 1 
Day 3 
Day 5 
Day 8 
Withdrawal 
visit5 
Safety Follow 
Up Visit6 
Long Term 
Follow Up 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
 
Pregnancy test3 
X 
X 
X 
 
Confirmation of Dx4 
X 
 
 
CT CAP and/or MRI 
X 
X 
X6 
X7 
CA 19-9 
X 
X 
X 
 
 
ECG 
X 
X 
X 
X 
 
Echocardiogram 
X 
 
 
Ambulatory Oxygen Saturation 
X 
 
 
 
 
 
 
 
Chest X-ray 
 
X8 
 
 
 
 
 
 
NIH Advance Directives Form7 
 
X9 
 
 
 
 
 
 
PKs 
 
Please refer to section 5.2.1 
 
 
 
Correlative Studies 
 
Please refer to section 5.2.1 
 
Annual phone call to monitor 
survival and additional CA therapy 
 
 
 
 
 
 
 
X 
Adverse events 
 
continuous 
X 
X 
 
Concomitant meds 
 
continuous 
 
 
 
1 
During the infusions of all study, vital signs (heart rate, blood pressure, oxygen saturation) have to be monitored pre-infusion and 
every 15 minutes (± 5 minutes) during the infusion and then every 30 minutes (± 10 minutes) until 2 hours post-infusion.  
2 
CBC with differential, Acute Care Panel, Hepatic Panel, Mineral Panel, ,  C-reactive protein (CRP), creatine kinase (CK), PT, PTT, 
LDH 


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Cycle 1 -2 
Post Therapy 
Procedure 
Screening 
Day 1 
Day 3 
Day 5 
Day 8 
Withdrawal 
visit5 
Safety Follow 
Up Visit6 
Long Term 
Follow Up 
3 
Pregnancy test required in women of childbearing potential; i.e. premenopausal women and women ≤ 2 years after menopause 
(menopause is defined as amenorrhea for > 2 years. 
4 
Assessment may occur at any time prior to enrollment 
5 
For participants who complete both cycles of therapy, the withdrawal visit should be scheduled for any time between Day 20 of and 
7 days following the end of Cycle 2. For participants who do not complete both cycles of therapy, the withdrawal visit should be 
scheduled 3-6 weeks from last treatment. Imaging studies do not need to be repeated if most recent were performed within the prior 
20 days.   
6 
Safety follow up will occur 3 – 6 weeks after last dose of study therapy in patients that have progressed. The safety assessment will 
occur 6 weeks +/-2 weeks after the previous scan in those that have stable disease, partial response or complete response. The 
assessments listed refer to those that will be performed if the patient is seen in clinic. If withdrawal visit occurred within this 
timeframe, it can be used as the safety follow up visit. If the patient is unable to return to the clinic for the follow up visit, an adverse 
event assessment will be performed by telephone. 
7 
Scans, every 6 weeks, will only be performed until disease progression. Note: for patients on long term follow up, scans may be 
performed outside of NIH. 
8 
Chest x-ray to be done within 7 days prior to treatment on cycle 1 only. 
9 
As indicated in section 9.3, all subjects will be offered the opportunity to complete an NIH advanced directives form. This should be 
done preferably at baseline but can be done at any time during the study as long as the capacity to do so is retained. The completion 
of the form is strongly recommended, but is not required. 
 
 


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3.4.2 Calendars subjects in Arm B1 (single agent continuous infusion LMB-100) 
3.4.2.1 24 HOUR INFUSION (on Day 1 OR Day 1 & 4) 
1 cycle = 21 days  
Unless otherwise indicated, screening assessments must occur within 28 days prior to enrollment.  Cycle 1, day 1 assessments with the exception of 
imaging studies may occur up to 3 days prior to treatment initiation.  Imaging studies must be completed ± 7 days from the indicated time. If 
screening assessments are performed within the appropriate timeframe for Cycle 1 Day 1 assessments, they do not need to be repeated on that day. 
Beyond cycle 1, performance status and standard laboratory assessments may be performed up to 1 day prior to the indicated time. 
Dosing cycles after cycle 1 may be delayed for up to one week to accommodate schedule conflicts, Federal holidays and inclement 
weather, etc. They may be delayed for up to two weeks due to toxicity. 
 
 
Cycle 1 & 2 
Post Therapy 
Procedure 
Screening 
Day 1 
Day 2 
Day 3 
Day 
4-5*  
Day 6* 
Day 8 
Withdrawal 
visit7 
Safety 
Follow 
Up 
Visit8 
Long 
Term 
Follow 
Up 
LMB-100 
 
X 
X 
 
X 
 
 
 
 
 
History and PE 
X 
X 
 
 
 
 
 
X 
X 
 
Weight 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height 
 
C1 only 
 
 
 
 
 
 
 
 
Vital signs1 
X 
X 
X 
X 
X 
X 
X1 
X 
X 
 
PS 
X 
X 
 
 
 
 
 
X 
 
 
Labs2 
X 
X 
X 
X 
X 
X 
X1 
X 
X 
 
1,25-dihydroxy Vit D 
X 
 
 
 
 
 
 
X 
 
 
Urinalysis 
X 
X 
X 
X 
X 
X 
X1 
X 
X 
 
Pregnancy test3 
X 
X 
 
 
 
 
 
 
X 
 
Confirmation of Dx4 
X 
  
  
  
  
  
  
  
  
  


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Cycle 1 & 2 
Post Therapy 
Procedure 
Screening 
Day 1 
Day 2 
Day 3 
Day 
4-5*  
Day 6* 
Day 8 
Withdrawal 
visit7 
Safety 
Follow 
Up 
Visit8 
Long 
Term 
Follow 
Up 
Assessment of tumor 
MSLN expression4,  
X 
  
  
  
  
  
  
  
  
  
CT CAP and/or MRI 
X 
 
X 
X9 
X9 
CA 19-95  
X 
X 
 
X 
 
 
ECG 
X 
X 
X 
 
 
 
X 
X 
 
Echocardiogram 
X 
 
 
 
Ambulatory Oxygen 
Saturation 
X 
 
 
 
Chest X-ray 
 
X10 
 
 
 
 
 
 
 
 
NIH Advance 
Directives Form6 
 
X6 
 
 
 
 
 
 
 
 
PKs 
  
                          Please refer to section 5.2.2.1 
 
 
  
Correlative Studies, 
including optional 
biopsy 
 
Please refer to section 5.2.2.1 
 
Annual phone call to 
monitor survival and 
additional CA therapy 
 
 
 
 
 
 
 
 
 
X 
Adverse events 
 
continuous 
X 
X 
 
Concomitant meds 
 
continuous 
 
 
 
 * For the D1&4 continuous infusion level only (and not for participants just getting 24 hr infusion on D1) 


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1 
During continuous infusion, vital signs including, if possible, supine diastolic and systolic blood pressure, pulse rate, and oxygen saturation) 
must be monitored pre-infusion, every 30 minutes (± 5 minutes) for the first two hours of the infusion beginning with the start of loading 
dose, and thereafter, every 6 hours (±60 minutes)  until the infusion finishes. Vital signs during the first 2 hours of infusion are not required 
to be captured in the eCRF unless abnormalities are observed. 
2 
CBC with differential, Acute Care Panel, Hepatic Panel, Mineral Panel, C-reactive protein (CRP), Creatine Kinase (CK), CK, PT, PTT, 
LDH 
3 
Pregnancy test required in women of childbearing potential; i.e. premenopausal women and women ≤ 2 years after menopause (menopause 
is defined as amenorrhea for > 2 years 
4 
Assessment may occur at any time prior to enrollment 
5 
For patients with diagnosis pancreatic or biliary cancers (cholangiocarcinoma) only 
6 
As indicated in section 9.3, all subjects will be offered the opportunity to complete an NIH advanced directives form.  This should be done 
preferably at baseline but can be done at any time during the study as long as the capacity to do so is retained.  The completion of the form 
is strongly recommended, but is not required. 
7 
For participants who complete both cycles of therapy, the withdrawal visit should be scheduled for any time between Day 20 of and 7 days 
following the end of Cycle 2.  For participants who do not complete both cycles of therapy, the withdrawal visit should be scheduled 3-6 
weeks from last treatment.  Imaging studies do not need to be repeated if most recent were performed within the prior 20 days.   
8 
Safety follow up will occur 3 – 6 weeks after last dose of study therapy in patients that have progressed. The safety assessment will occur 6 
weeks +/-2 weeks after the previous scan in those that have stable disease, partial response or complete response. The assessments listed 
refer to those that will be performed if the patient is seen in clinic. If withdrawal visit occurred within this timeframe, it can be used as the 
safety follow up visit.  If the patient is unable to return to the clinic for the follow up visit, an adverse event assessment will be performed 
by telephone. 
9 
Scans, every 6 weeks, will only be performed until disease progression. Note:  for patients on long term follow up, scans may be performed 
outside of NIH. 
10 Chest x-ray to be done within 7 days prior to treatment on cycle 1 only 
 
 


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3.4.2.2 48 HOUR INFUSION 
Unless otherwise indicated, screening assessments must occur within 28 days prior to enrollment.  Cycle 1, day 1 assessments with the exception of 
imaging studies may occur up to 3 days prior to treatment initiation.  Imaging studies must be completed ± 7 days from the indicated time. If 
screening assessments are performed within the appropriate timeframe for Cycle 1 Day 1 assessments, they do not need to be repeated on that day. 
Beyond cycle 1, performance status and standard laboratory assessments may be performed up to 1 day prior to the indicated time. 
Dosing cycles after cycle 1 may be delayed for up to one week to accommodate schedule conflicts, Federal holidays and inclement weather, etc. 
They may be delayed for up to two weeks due to toxicity. 
  
Cycle 1 & 2 
Post Therapy 
Procedure 
Screening 
Day 1 
Day 2-3 
Day 4 
Day 5 
Day 8 
Withdraw
al visit7 
Safety 
Follow 
Up Visit8 
Long 
Term 
Follow 
Up 
LMB-100 
X 
X 
 
 
 
History and PE 
X 
X 
 
 
 
 
X 
X 
 
Weight 
 
X 
X 
X 
 
X 
X 
X 
 
Height 
 
C1 only 
 
 
 
 
 
 
 
Vital signs1 
X 
X 
X 
X 
 
X1 
X 
X 
 
PS 
X 
X 
 
 
 
 
X 
 
 
Labs2 
X 
X 
X 
X 
 
X1 
X 
X 
 
1,25-dihydroxy Vit D 
X 
 
 
 
 
 
X 
 
 
Urinalysis 
X 
X 
X 
X 
 
X1 
X 
X 
 
Pregnancy test3 
X 
X 
 
 
 
 
 
X 
 
Confirmation of Dx4 
X 
 
 
 


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Cycle 1 & 2 
Post Therapy 
Procedure 
Screening 
Day 1 
Day 2-3 
Day 4 
Day 5 
Day 8 
Withdraw
al visit7 
Safety 
Follow 
Up Visit8 
Long 
Term 
Follow 
Up 
Assessment of tumor MSLN 
expression4,  
X 
 
 
 
 
 
 
 
 
CT CAP and/or MRI 
X 
 
X 
X9 
X9 
CA 19-95  
X 
X 
 
X 
 
 
ECG 
X 
X 
Day 3 
only 
 
X 
X 
 
Echocardiogram 
X 
 
 
 
 
 
 
 
 
Ambulatory Oxygen 
Saturation 
X 
 
 
 
 
 
 
 
 
Chest X-ray 
 
X10 
 
 
 
 
 
 
 
NIH Advance Directives 
Form6 
 
X6 
 
 
 
 
 
 
 
PKs 
 
Please refer to section 5.2.2.2 
 
 
 
Correlative Studies, 
including optional biopsy 
 
Please refer to section 5.2.2.2 
 
Annual phone call to 
monitor survival and 
additional CA therapy 
 
 
 
 
 
 
 
 
X 
Adverse events 
continuous 
X 
X 
 


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Cycle 1 & 2 
Post Therapy 
Procedure 
Screening 
Day 1 
Day 2-3 
Day 4 
Day 5 
Day 8 
Withdraw
al visit7 
Safety 
Follow 
Up Visit8 
Long 
Term 
Follow 
Up 
Concomitant meds 
continuous 
 
 
1 
During continuous infusion, vital signs including, if possible, supine diastolic and systolic blood pressure, pulse rate, and oxygen saturation) must be 
monitored pre-infusion, every 30 minutes (± 5 minutes) for the first two hours of the infusion beginning with the start of loading dose, and thereafter, 
every 6 hours (±60 minutes)  until the infusion finishes. Vital signs during the first 2 hours of infusion are not required to be captured in the eCRF unless 
abnormalities are observed. 
2 
CBC with differential, Acute Care Panel, Hepatic Panel, Mineral Panel, , C-reactive protein (CRP), Creatine Kinase (CK), PT, PTT, LDH 
3 
Pregnancy test required in women of childbearing potential; i.e. premenopausal women and women ≤ 2 years after menopause (menopause is defined as 
amenorrhea for > 2 years 
4 
Assessment may occur at any time prior to enrollment 
5 
For patients with diagnosis pancreatic or biliary cancers (cholangiocarcinoma) only 
6 
As indicated in section 9.3, all subjects will be offered the opportunity to complete an NIH advanced directives form.  This should be done preferably at 
baseline but can be done at any time during the study as long as the capacity to do so is retained.  The completion of the form is strongly recommended, 
but is not required. 
7 
For participants who complete both cycles of therapy, the withdrawal visit should be scheduled for any time between Day 20 of and 7 days following the 
end of Cycle 2.  For participants who do not complete both cycles of therapy, the withdrawal visit should be scheduled 3-6 weeks from last treatment.  
Imaging studies do not need to be repeated if most recent were performed within the prior 20 days.   
8 
Safety follow up will occur 3 – 6 weeks after last dose of study therapy in patients that have progressed. The safety assessment will occur 6 weeks +/-2 
weeks after the previous scan in those that have stable disease, partial response or complete response. The assessments listed refer to those that will be 
performed if the patient is seen in clinic. If withdrawal visit occurred within this timeframe, it can be used as the safety follow up visit.  If the patient is 
unable to return to the clinic for the follow up visit, an adverse event assessment will be performed by telephone. 
9 
Scans, every 6 weeks, will only be performed until disease progression. Note:  for patients on long term follow up, scans may be performed outside of 
NIH. 
10 
Chest x-ray to be done within 7 days prior to treatment on cycle 1 only 
 
 
 


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3.4.3  Calendar for Subjects in Arm B2 (LMB-100 24-hour continuous infusion combination therapy) 
1 cycle = 14 days  
Unless otherwise indicated, screening assessments must occur within 28 days prior to enrollment.  Cycle 1, day 1 assessments with the exception of 
imaging studies may occur up to 3 days prior to treatment initiation.  Imaging studies must be completed ± 7 days from the indicated time. If 
screening assessments are performed within the appropriate timeframe for Cycle 1 Day 1 assessments, they do not need to be repeated on that day. 
Beyond cycle 1, performance status and standard laboratory assessments may be performed up to 1 day prior to the indicated time. 
Dosing cycles after cycle 1 may be delayed for up to one week to accommodate schedule conflicts, Federal holidays and inclement 
weather, etc. They may be delayed for up to two weeks due to toxicity. 
 
  
  
All cycles 
Post Therapy 
Procedure 
Screening 
Day 1 
Day 2 
Day 3 
Withdrawal 
visit7 
Safety 
Follow Up 
Visit8 
Long Term 
Follow Up 
Nab-paclitaxel 
 
X 
 
 
 
 
 
LMB-100 
 
X 
X 
 
 
 
 
History and PE 
X 
X 
 
 
X 
X 
 
Weight 
 
X 
X 
C1 only 
X 
X 
 
Height 
 
C1 only 
 
 
 
 
 
Vital signs1 
X 
X 
X 
C1 only 
X 
X 
 
PS 
X 
X 
 
 
X 
 
 
Labs2 
X 
X 
X 
C1 only 
X 
X 
 
1,25-dihydroxy Vit D 
X 
 
 
 
X 
 
 
Hepatitis and HIV screening 
panel 
X 
 
 
Urinalysis 
X 
X 
X 
C1 only 
X 
X 
 


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All cycles 
Post Therapy 
Procedure 
Screening 
Day 1 
Day 2 
Day 3 
Withdrawal 
visit7 
Safety 
Follow Up 
Visit8 
Long Term 
Follow Up 
Pregnancy test3 
X 
X 
X 
 
Confirmation of Dx4 
X 
  
  
  
  
  
CT CAP and/or MRI 
X 
 
 
 
X 
X9 
X9 
CA 19-95 
X 
X 
X 
 
 
ECG 
X 
X 
X 
 
X 
X 
 
Echocardiogram 
X 
  
 
Ambulatory Oxygen Saturation 
X 
 
 
 
 
 
 
Chest X-ray 
 
X10 
 
 
 
 
 
NIH Advance Directives Form6 
 
X6 
 
 
 
 
 
PKs 
  
Please refer to section 5.2.2.1 
 
 
  
Correlative Studies, including 
optional biopsy 
 
Please refer to section 5.2.2.1 
 
 
Annual phone call to monitor 
survival and additional CA 
therapy 
 
 
 
 
 
 
X 
Adverse events 
 
continuous 
X 
X 
 
Concomitant meds 
 
continuous 
 
 
 
1 
During continuous infusion, vital signs including, if possible, supine diastolic and systolic blood pressure, pulse rate, and oxygen saturation) 
must be monitored pre-infusion, every 30 minutes (± 5 minutes) for the first two hours of the infusion beginning with the start of loading 


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dose, and thereafter, every 6 hours (±60 minutes) until the infusion finishes. Vital signs during the first 2 hours of infusion are not required 
to be captured in the eCRF unless abnormalities are observed. 
2 
CBC with differential, Acute Care Panel, Hepatic Panel, Mineral Panel, C-reactive protein (CRP), Creatine Kinase (CK), CK, PT, PTT, 
LDH 
3 
Pregnancy test required in women of childbearing potential; i.e. premenopausal women and women ≤ 2 years after menopause (menopause 
is defined as amenorrhea for > 2 years 
4 
Assessment may occur at any time prior to enrollment 
5 
For patients with diagnosis pancreatic or biliary cancers (cholangiocarcinoma) only 
6 
As indicated in section 9.3, all subjects will be offered the opportunity to complete an NIH advanced directives form.  This should be done 
preferably at baseline but can be done at any time during the study as long as the capacity to do so is retained.  The completion of the form 
is strongly recommended, but is not required. 
7 
For participants who complete all cycles of therapy, the withdrawal visit should be scheduled for any time between Day 20 of and 7 days 
following the end of Cycle 2.  For participants who do not complete all cycles of therapy, the withdrawal visit should be scheduled 3-6 
weeks from last treatment.  Imaging studies do not need to be repeated if most recent were performed within the prior 20 days.   
8 
Safety follow up will occur 3 – 6 weeks after last dose of study therapy in patients that have progressed. The safety assessment will occur 6 
weeks +/-2 weeks after the previous scan in those that have stable disease, partial response or complete response. The assessments listed 
refer to those that will be performed if the patient is seen in clinic. If withdrawal visit occurred within this timeframe, it can be used as the 
safety follow up visit.  If the patient is unable to return to the clinic for the follow up visit, an adverse event assessment will be performed 
by telephone. 
9 
Scans, every 6 weeks, will only be performed until disease progression. Note:  for patients on long term follow up, scans may be performed 
outside of NIH. 
10 Chest x-ray to be done within 7 days prior to treatment on cycle 1 only 
 
 


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3.5 
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA 
Prior to removal from study, effort must be made to have all subjects complete a safety visit as 
indicated in the Study Calendar following the last dose of study therapy. 
3.5.1 Criteria for removal from protocol therapy 
x Progressive disease 
x Participant has completed planned number of cycles of study therapy 
x Participant requests to be withdrawn from active therapy 
x Pregnancy 
x Unacceptable Toxicity as defined in sections 3.1.2 and 3.3 
x Investigator discretion 
3.5.2 Off-Study Criteria 
x Screen failure 
x Participant lost to follow-up 
x Participant requests to be withdrawn from study 
x Death 
3.5.2.1 Off Protocol Therapy and Off-Study Procedure 
Authorized staff must notify Central Registration Office (CRO) when a subject is taken off 
protocol therapy and when a subject is taken off-study. A Participant Status Updates Form from 
the website (http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) main page must be 
completed and sent via encrypted email to:  NCI Central Registration Office 
ncicentralregistration-l@mail.nih.gov. 
4 
CONCOMITANT MEDICATIONS/MEASURES 
4.1.1 Permitted Therapy 
Concomitant therapy includes any medication (e.g., prescription drugs, over-the-counter (OTC) 
drugs, approved dietary and herbal supplements, nutritional supplements) used by a participant 
from the screening period until the follow-up visit. If any treatment is given within 4 weeks prior 
to screening this should be reported to the investigator and recorded in the eCRF. 
All therapy and/or medication administered to manage adverse events should be recorded on the 
Adverse Event eCRF. 
4.1.2 Prohibited Therapy 
Participants should be treated for all concomitant conditions and adverse events according to 
accepted standards of medical care at the discretion of the investigator. The following treatments 
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x Any other investigational therapy 
x Cytotoxic chemotherapy agents other than nab-paclitaxel 
x Radiotherapy. Note: palliative 8Gy radiotherapy is allowed. 
x Immunosuppressive therapy and chronically administered glucocorticoids (high dose is 
considered as !20 mg of dexamethasone a day [or equivalent)] for !7 consecutive days)  
x Other systemic anti-neoplastic agents and targeted therapies 
If any anti-neoplastic or investigational therapies listed above are needed, the participant will be 
considered to have evidence of progressive neoplastic disease and have experienced treatment 
failure with study treatment and should be withdrawn from study treatment. 
Caution should be exercised when drugs that are known to be substrates (e.g., midazolam, 
buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, and triazolam), inhibitors (e.g., 
atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, 
saquinavir, and telithromycin), and inducers (e.g., rifampin and carbamazepine) of CYP3A4 are to 
be co-administered with paclitaxel. Caution should also be exercised when paclitaxel is 
concomitantly administered with known substrates (e.g., repaglinide and rosiglitazone), inhibitors 
(e.g., gemfibrozil), and inducers (e.g., rifampin) of CYP2C8. 
All concomitant treatments must be documented in the eCRF. 
5 
BIOSPECIMEN COLLECTION 
5.1 
CORRELATIVE STUDIES FOR RESEARCH/PHARMACOKINETIC STUDIES 
5.1.1 LMB-100 Pharmacokinetic Assessments 
All blood samples for PK assessment will be collected from an IV line different to that receiving 
the infusion to measure free and total concentrations for LMB-100 for all patients. The date and 
time of each sample collection will be recorded. If multiple samples are drawn at a given time 
point, the PK sample should take precedence. 
Free and total plasma concentrations of LMB-100 will be measured using validated ligand-binding 
assays. 
5.1.1.1 Sample collection: 
Blood will be collected in 2 mL K2EDTA tubes (purple top) at the times defined in section 5.2. 
Samples should be inverted 8 to 10 times after collection.  Store on wet ice or at 4°C.  Processing 
within 60 minutes of blood collection is highly preferred.   
5.1.1.2 Sample processing 
Samples will be processed in the Clinical Pharmacology Program.  
Please e-mail NCIBloodcore@mail.nih.gov at least 24 hours before transporting samples (the 
Friday before is preferred). 
For sample pickup, page 102-11964. 
For immediate help, call 240-760-6180 (main blood processing core number) or, if no answer, 
240-760-6190 (main clinical pharmacology lab number). 


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For questions regarding sample processing, contact NCIBloodcore@mail.nih.gov. 
Upon arrival in the CPP the following procedures should be followed: 
1. Store on wet ice until centrifugation.  
2. Centrifuge 1500xg for 10 minutes at 4°C within 60 minutes of blood collection.  
3. Transfer plasma specimen to 2mL cryovials and store at -70°C.   
The analyses will be performed retrospectively in batched samples or at the end of the trial. 
5.1.1.3 Sample Shipping 
Samples will be shipped by the CPP on dry ice to Ms. Yanyu Wang in Frederick for analysis. 
Leidos Biomedical, Inc. 
Attention: Ms. Yanyu Wang and Dr. Jon Inglefield. 
Building 469, Room 200 
Miller Drive 
Frederick, MD 21702 
Phone: 301-846-6905/301-846-6865 
5.1.1.4 Sample storage 
Samples will be stored in the CPP until shipment to the Leidos Biomedical Inc. Lab in Frederick.  
5.1.2 Nab-Paclitaxel Pharmacokinetic Assessments 
Blood samples for the determination of plasma levels of abraxane (nab-paclitaxel) will be obtained 
from each patient receiving nab-paclitaxel as directed in section 5.2.   
Bioanalytical measurements will be conducted on an ultra HPLC-MSMS system using an assay 
developed and validated by the Clinical Pharmacology Program. 
This data will be used to monitor nab-paclitaxel plasma concentrations both in the absence and 
presence of LMB-100 to assess any drug interactions as well as correlate to pharmacodynamic 
endpoints, clinical response, toxicity, and pharmacogenetic analyses.  
5.1.2.1 Sample Collection 
See section 5.2 for schedule, volumes and tube types. Blood samples will be inverted 4-5x then 
placed on wet ice until a member of the Blood Processing Core can pick them up and process into 
plasma for database entry, aliquoting and storage. Paclitaxel is stable in blood on wet ice overnight, 
if needed. 
5.1.2.2 Sample processing 
Samples will be processed in the Clinical Pharmacology Program.  
Please e-mail NCIBloodcore@mail.nih.gov at least 24 hours before transporting samples (the 
Friday before is preferred). 
For sample pickup, page 102-11964. 
For immediate help, call 240-760-6180 (main blood processing core number) or, if no answer, 
240-760-6190 (main clinical pharmacology lab number). 


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For questions regarding sample processing, contact NCIBloodcore@mail.nih.gov. 
5.1.2.3 Sample storage 
Samples will be stored in the CPP. 
5.1.3 Pharmacogenetic Studies 
Pharmacogenetic studies will be performed to analyze the genomic DNA and assess the genotype 
of the most relevant drug metabolizing enzymes and transporters (DMET). DNA will be analyzed 
on a DMET Plus (Affymatrix) genotyping platform that tests for 1,936 genetic variations in 225 
drug disposition genes, including 47 CYP (phase I metabolism) genes, 13 non-CYP (phase I 
metabolism) genes, 78 phase II metabolizing genes (including UGTs), 63 transporters, 4 genes 
involved in facilitation of drug transporters, 9 genes involved in global regulation of drug 
metabolizing/transporting proteins, 4 drug binding proteins, and 4 drug targets. 
Of specific interest to nab-paclitaxel are polymorphisms in CYP2C8, CYP3A4/5, and ABCB1, all 
of which are included in the DMET analysis.   
Studies will be performed by the Clinical Pharmacology Program.  
5.1.3.1 Sample Collection 
One blood sample will be collected per patient. See section 5.2 for timing, volume and tube type. 
5.1.3.2 Sample processing 
Samples will be processed in the Clinical Pharmacology Program.  
Please e-mail NCIBloodcore@mail.nih.gov at least 24 hours before transporting samples (the 
Friday before is preferred). 
For sample pickup, page 102-11964. 
For immediate help, call 240-760-6180 (main blood processing core number) or, if no answer, 
240-760-6190 (main clinical pharmacology lab number). 
For questions regarding sample processing, contact NCIBloodcore@mail.nih.gov. 
5.1.3.3 Sample storage 
Samples will be stored in the CPP. 
5.1.4 Assessment of anti-drug antibodies (ADAs)  
5.1.4.1 Sample Collection   
Samples will be collected before the first dose of LMB-100 administration during each cycle. (See 
section 5.2)  
Draw 2mL into K2EDTA tube (purple top).  Samples should be inverted 8 to 10 times after 
collection. Store on wet ice or at 4°C. Processing within 60 minutes of blood collection is highly 
preferred. 
5.1.4.2 Sample Processing  
Samples will be processed in the Clinical Pharmacology Program.  


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67 
 
Please e-mail NCIBloodcore@mail.nih.gov at least 24 hours before transporting samples (the 
Friday before is preferred). 
For sample pickup, page 102-11964. 
For immediate help, call 240-760-6180 (main blood processing core number) or, if no answer, 
240-760-6190 (main clinical pharmacology lab number). 
For questions regarding sample processing, contact NCIBloodcore@mail.nih.gov.    
Upon arrival in the CPP, each sample should be processed in the following manner:  
1. Store on wet ice until centrifugation.   
2. Centrifuge 1500xg for 10 minutes at 4°C within 60 minutes of blood collection.  
3. Transfer plasma specimen to 2mL cryovials and store at -70°C.   
Autoantibody levels will be retrospectively assessed. 
5.1.4.3 Sample Shipping 
Samples will be shipped by the CPP on dry ice to Ms. Yanyu Wang in Frederick for analysis. 
Leidos Biomedical, Inc. 
Attention: Ms. Yanyu Wang and Dr. Jon Inglefield. 
Building 469, Room 200 
Miller Drive 
Frederick, MD 21702 
Phone: 301-846-6905/301-846-6865 
5.1.4.4 Sample Storage 
Samples will be stored in the CPP until shipment to the Leidos Biomedical Inc. Lab in Frederick.   
5.1.5 Retrospective Analysis of Mesothelin Expression in tumor tissue 
IHC analysis will be performed by the Laboratory of Pathology at NCI to determine mesothelin 
expression within the tumor at any time after study enrollment.  Leftover tissue from archival 
specimens or tumor biopsies obtained at screening will be used for analysis. Specimens will be 
used to correlate treatment with response with mesothelin expression in an exploratory analysis.  
5.1.6 Cytokines for identification of mechanism for PE-mediated capillary leak syndrome 
PE-based RITs cause dose-limiting CLS. At low doses CLS manifests as mild and transient weight 
gain, hypoalbuminemia, and peripheral or facial edema.  At higher doses it can cause life-
threatening cardiopulmonary compromise. Previous studies in rats have indicated that pathological 
changes indicative of CLS onset occur within just two hours of toxin administration and even when 
the PE fragment lacks a targeting domain.[41] In vitro studies with cultured endothelial cells have 
demonstrated that super-physiologic doses of PE-based RITs cannot induce endothelial cell 
toxicity unless the cells express the RIT target.[42] Together these data suggest the hypothesis that 
PE-based RITs cause CLS by triggering release of vasoactive cytokines by specific immune 
cells rather than through direct damage to endothelial cells. To test this hypothesis, we will 
collect additional serum from participants during the first hours of standard PK measurements on 


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Cycle 1 Day 1 of treatment (see section 5.2 for specific time points).  Samples will be stored for 
later analysis.   
5.1.6.1 Specimen collection  
To test this hypothesis, we will collect additional serum from participants on the days and 
timepoints shown in sections 5.2.1 and 5.2.2 respectively for short infusion and continuous 
infusion cohorts. 
5.1.6.2 Sample processing 
Serum collected at some time points will also be used for serum MPF measurements (see Section 
5.1.11) and must be aliquoted appropriately to complete both assays. 
Please e-mail NCIBloodcore@mail.nih.gov at least 24 hours before transporting samples (the 
Friday before is preferred). 
For sample pickup, page 102-11964. 
For immediate help, call 240-760-6180 (main blood processing core number) or, if no answer, 
240-760-6190 (main clinical pharmacology lab number). 
For questions regarding sample processing, contact NCIBloodcore@mail.nih.gov. 
Cytokine levels will be retrospectively assessed. 
5.1.7 Circulating endothelial cells (CEP and CEC) for identification of mechanism for PE-
mediated capillary leak syndrome 
Circulating endothelial progenitor cells (CEP) and mature circulating endothelial cells (CEC) will 
be assessed by multiparameter flow cytometry. Cells will be analyzed for forward and side scatter, 
and cells expressing hematopoietic markers will be excluded.  Endothelial cells will be identified 
using co-expression of markers, such as CD31 and CD146 for CEC, and CD31 and CD133 for 
CEP. The cell populations will also be analyzed for viability using scatter profiles and a vital stain, 
such as Hoechst 33258. Percentages of stained cells will be determined and compared with 
appropriate negative controls. Multiparameter flow cytometric analysis will be performed with a 
Miltenyi Quant equipped with FlowJo software, using a minimum of 100,000 events per analysis. 
5.1.7.1 Sample Collection 
Draw blood into one 8-cc CPT citrate (BD) tube at (1) baseline, just prior to beginning therapy, 
(2) cycle 1 at 16 to 30 hours following end of last infusion as specified in sections 5.2.1 and 5.2.2, 
and (3) cycle 2 day 1, prior to therapy.   
5.1.7.2 Sample Processing 
Contact the Trepel Lab, Developmental Therapeutics Branch, NCI by email (Jane Trepel- 
trepel@helix.nih.gov; and Sunmin Lee- lees@pop.nci.nih.gov) when the patient is scheduled and 
by phone as soon as the blood is drawn at 240 760 6330and a lab member will pick up the sample.  
5.1.8 Immune subset analysis 
Peripheral blood mononuclear cells (PBMC) will be assessed using multiparameter flow cytometry 
for immune subsets including but not necessarily limited to CD8+ T-cells, CD4+Foxp3- T-cells, 


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Tregs, Th1, Th2 and Th17+ CD4+ T-cells, monocyte subsets, MDSC subsets. Assessment will 
include functional markers, i.e. PD-1, Tim-3, CTLA-4, PD-L1, HLA-DR and/or CD40.  
5.1.8.1 Sample Collection 
Draw blood into two 8-cc CPT citrate (BD) tubes at (1) baseline, just prior to beginning therapy, 
(2) cycle 1 following end of last infusion as specified in sections 5.2.1 and 5.2.2 , and (3) cycle 2 
day 1, prior to therapy.   
5.1.8.2 Sample Processing 
Contact the Trepel Lab, Developmental Therapeutics Branch, NCI by email (Jane Trepel- 
trepel@helix.nih.gov; 
Yusuke 
Tomita- 
yusuke.tomita@nih.gov 
and 
Sunmin 
Lee- 
lees@pop.nci.nih.gov) when the patient is scheduled and by phone as soon as the blood is drawn 
at 240 760 6330. Please phone the lab as soon as it is drawn and a lab member will come to pick 
up the blood.  Please keep blood at ambient temperature.  
Members of the lab will enter the samples in a secure patient database, process the samples for 
viable cell storage, label each sample with a unique 2D barcode, and viably store the samples. 
They will prepare the samples for staining, stain and run the samples by multiparametric flow 
cytometry (MACSQuant, Miltenyi Biotec, Bergisch Gladbach, DE), and analyze the data using 
FlowJo (FlowJo LLC, Ashland, OR) software.   
5.1.9 Peripheral blood immune gene expression 
Peripheral blood immune gene expression will be evaluated by the Trepel Lab using the 
NanoString nCounter® platform (NanoString Technologies, Seattle, WA). Collect peripheral 
blood in a PAXgene Blood RNA tube (PreAnalytix; 2.5 cc peripheral blood per tube) per the 
manufacturer’s instructions.  After the blood is drawn, the tube should be inverted several times 
and placed at room temperature.  RNA will be isolated using the PAXgene Blood RNA Kit 
according to the manufacturer’s instructions.  Peripheral immune gene expression will be 
evaluated using the PanCancer Immune Profiling codeset of 730 immune genes and 40 control 
genes at baseline and post-therapy by the Trepel Lab to look for correlates of clinical response 
with innate or adaptive immunity. 
5.1.9.1 Sample Collection  
Draw blood into one 2.5 ml PAXgene RNA tube at (1) baseline, just prior to beginning therapy, 
(2) cycle 1 following end of last infusion as specified in sections 5.2.1 and 5.2.2, and (3) cycle 2 
day 1, prior to therapy.   
5.1.9.2 Sample Processing 
Contact the Trepel Lab, Developmental Therapeutics Branch, NCI by email (Jane Trepel- 
trepel@helix.nih.gov; 
Yusuke 
Tomita- 
yusuke.tomita@nih.gov 
and 
Sunmin 
Lee- 
lees@pop.nci.nih.gov) when the patient is scheduled and by phone as soon as the blood is drawn 
at 240-760-6330. Please phone the lab as soon as it is drawn and a lab member will come to pick 
up the blood. 


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5.1.10 Circulating tumor cells 
Peripheral blood will be collected to correlate changes in circulating tumor cells with clinical 
response as well as to assess immune-mediated cell death.  CTCs will be assessed using ferrofluidic 
enrichment and multi-parameter flow cytometric detection. CTCs are identified by positive 
expression of epithelial markers and a viability marker and negative expression of hematopoietic 
markers.  
5.1.10.1 Sample Collection 
Draw blood into two 7.5 ml Veridex CellSave tubes at (1) baseline, just prior to beginning therapy, 
(2) cycle 1 following end of last infusion as specified in sections 5.2.1 and 5.2.2 and (3) cycle 2 
day 1, prior to therapy.   
5.1.10.2 Sample Processing 
Contact the Trepel Lab, Developmental Therapeutics Branch, NCI by email (Jane Trepel- 
trepel@helix.nih.gov; 
Yusuke 
Tomita- 
yusuke.tomita@nih.gov 
and 
Sunmin 
Lee- 
lees@pop.nci.nih.gov) when the patient is scheduled and by phone as soon as the blood is drawn 
at 240-760-6330 and a lab member will come to pick up the blood.  Please keep blood at ambient 
temperature. Members of the lab will enter the samples in a secure patient database, and process 
the samples for immediate CTC assessment. They will prepare the samples for staining, stain and 
run the samples by multiparametric flow cytometry (MACSQuant, Miltenyi Biotec, Bergisch 
Gladbach, DE), and analyze the data using FlowJo (FloJo LLC, Ashland, OR) software. 
5.1.11 Treatment Effect on Tumor Microenvironment 
An optional biopsy may be collected in Arm B1 on day 8 of cycle 2 and in arm B2on day 3 of 
cycle 2 in order to analyze any changes in the tumor microenvironment, pre and post.  The C2 D8 
samples will be collected in Interventional Radiology, using image guidance techniques, including 
CT guidance, as required.  Biopsies will be obtained from primary tumor sites and/or metastatic sites 
(if applicable). No more than 4 cores may be obtained per site. The biopsies collected post-treatment 
will be compared to those collected at the time of enrollment (section 5.1.5).  The samples will be 
assessed by immunohistochemistry in the NCI Laboratory of Pathology. 
5.1.12 Serum Megakaryocyte Potentiating Factor (MPF) level 
MPF is a second protein product produced by the MSLN gene.  This product is secreted by the cell 
and can be detected in the circulation in some patients. We hypothesize that serum MPF level may 
be used as a marker of tumor response in patients with MSLN-producing tumors like pancreatic 
cancer.  Also, because LMB-100 halts tumor cell protein synthesis, we hypothesize that during the 
time of treatment serum MPF levels may also decline due to LMB-100 effect on tumor cells. To 
test our first hypothesis, we will collect serum from participants pre-dose for C1 and C2 as well as 
at the conclusion of the study.  To address our second hypothesis, we will collect serum at the end 
of infusion (see section 5.2 for specific time points).  Samples will be stored for later analysis in 
the Cao lab.   


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5.1.12.1 Specimen collection  
To test this hypothesis, we will collect additional serum from participants in 4 mL red SST tubes 
at the following time-points: Cycle 1 Day 1 pre-dose, Cycle 1 at end of infusion, Cycle 2 Day 1 
pre-dose, and at the time of progression or withdrawal from study.   
5.1.12.2 Sample processing 
Serum collected at some time points will also be used for serum cytokine analysis (see Section 
5.1.6).  For serum MPF analysis, aliquot 100 μL each into two cryovials with printed labels and a 
sample identifier and store at -80°C. Coded, linked samples will be provided to the laboratory of 
Liang Cao upon request of the PI. 
Please e-mail NCIBloodcore@mail.nih.gov at least 24 hours before transporting samples (the 
Friday before is preferred). 
For sample pickup, page 102-11964. 
For immediate help, call 240-760-6180 (main blood processing core number) or, if no answer, 
240-760-6190 (main clinical pharmacology lab number). 
For questions regarding sample processing, contact NCIBloodcore@mail.nih.gov.


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5.2 
SAMPLE COLLECTION SCHEDULE 
5.2.1 Sample Collection for Patients receiving short infusion LMB-100 (Arms A1 and A2) 
Timed samples should be collected within +/- 15 minutes of indicted time, except for nab-paclitaxel PKs collections drawn at 5 or more hours after 
the end of infusion.  For these, samples should be collected with + / - 60 minutes of indicated time. 
Cycle 
Day 
LMB-100 
PKs  
(5.1.1) 
Nab-paclitaxel 
PKs 
(5.1.2) 
Pharmacogenetic 
studies 
(5.1.3) 
ADA  
(5.1.2) 
PE mediated 
CLS 
(Cytokines) 
and serum 
MPF level 
(5.1.6, 5.1.12) 
CECs, Immune 
Subsets, 
CTCs 
(5.1.7, 5.1.8, 
5.1.10) 
Immune 
gene 
expression 
(5.1.9) 
Tumor 
Sample 
(5.1.5) 
2 mL 
K2EDTA 
tube 
4 mL in 6 mL 
sodium heparin 
tube 
4-6 mL in purple 
top tube 
2 mL 
K2EDTA 
tube 
4 mL red SST 
tube 
Two 7.5 mL 
Veridex 
CellSave & three 
8 mL CPT citrate 
tubes 
2.5 mL 
PAXgene 
RNA tube 
NA 
Screening 
Screening  
  
 
 
  
  
 
 
Xa 
1 
1 
Pre-dose, 
EOI, 1, 2, 
and 4 
hours after 
EOI 
pre-infusion, half 
way through 
infusion (15-min), 
2-5min prior to 
EOI (25-28min), 
EOI, and 0.5, 1, 2, 
5, 8, 12, 24, 48 and 
72 hr post dose.   
Xb 
Pre-dose 
Pre-dose, EOI, 
1, 2 and 4 hours 
after EOI 
Pre-dose 
Pre-dose 
 
2 
 
 
 
 
 
 
 
 
3  
Pre-dose, 
EOIc 
 
 
  
 
 
 
 
5 
 
 
 
 
EOI 
 
 
 
6 
 
 
 
 
 
Xd 
Xd 
 


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Cycle 
Day 
LMB-100 
PKs  
(5.1.1) 
Nab-paclitaxel 
PKs 
(5.1.2) 
Pharmacogenetic 
studies 
(5.1.3) 
ADA  
(5.1.2) 
PE mediated 
CLS 
(Cytokines) 
and serum 
MPF level 
(5.1.6, 5.1.12) 
CECs, Immune 
Subsets, 
CTCs 
(5.1.7, 5.1.8, 
5.1.10) 
Immune 
gene 
expression 
(5.1.9) 
Tumor 
Sample 
(5.1.5) 
2 mL 
K2EDTA 
tube 
4 mL in 6 mL 
sodium heparin 
tube 
4-6 mL in purple 
top tube 
2 mL 
K2EDTA 
tube 
4 mL red SST 
tube 
Two 7.5 mL 
Veridex 
CellSave & three 
8 mL CPT citrate 
tubes 
2.5 mL 
PAXgene 
RNA tube 
NA 
2 
1 
Pre-dose, 
EOI 
 
 
Pre-dose 
Pre-dose 
Pre-dose 
Pre-dose 
 
3  
Pre-dose, 
EOIc 
 
 
  
 
 
 
 
At time of 
Progression 
 
 
 
 
X 
X 
 
 
 
Withdrawal Visit 
  
  
 
 
X 
X 
 
 
 
Safety Follow-up 
Visit  
  
  
 
 
X 
X 
 
 
 
ADA =anti-drug antibody; EOI =End of infusion; PK =pharmacokinetic; CTC=circulating tumor cell; CEC=circulating endothelial cell 
a. 
Archival tissue collection or biopsy if no tissue available (mandatory).  
b. 
Collected preferably at baseline, but may be collected at any time during the study. 
c. 
Required only for patients on Arm A1.  May alternatively be drawn on day 5 to avoid a weekend draw. 
d. 
May alternatively be drawn post treatment on C1D5 to avoid a weekend draw 
 
 


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5.2.2 Sample Collection for Patients receiving continuous infusion of LMB-100 (Arms B1 and B2) 
5.2.2.1 24-hour continuous infusion 
Timed samples scheduled for within 4 hours after reference point (start of infusion or end of infusion) should be collected within +/- 15 minutes of 
indicted time.  Those collected 4 or more hours after reference point (start of infusion or end of infusion) may be collected within +/- 60 minutes of 
indicated time.  
Cycle 
Day 
LMB-100 
PKs (5.1.1)  
Nab-paclitaxel 
PKsa (5.1.2) 
Pharmacogenetic 
studies (5.1.3) 
ADA 
(5.1.2)  
PE mediated 
CLS (Cytokines) 
and serum MPF 
level 
 (5.1.6, 5.1.12) 
CECs, Immune 
Subsets, CTCs 
(5.1.7, 5.1.8, 
5.1.10) 
Immune 
gene 
expression 
(5.1.9) 
Tumor 
Sample 
(5.1.5, 5.1.11) 
2 mL 
K2EDTA 
tube 
4mL in 6 mL 
sodium heparin 
tube 
4-6 mL in purple 
top tube 
2 mL 
K2ED
TA 
tube 
4 mL red SST 
tube 
Two 
7.5 
mL 
Veridex 
CellSave 
& three 8 mL CPT 
citrate tubes 
2.5 mL 
PAXgene 
RNA tube 
NA 
Screening 
Screening  
  
  
  
  
  
  
  
Xb 
1 
1 
Pre-dose, 
End of 
loading 
dose, 2, 
and 6 hours 
after start 
of 
continuous 
infusion 
Pre-infusion, 
half way 
through dose 
(~15-min), 2-5 
min prior to 
EOI(~25-
28min), EOI, 
and 0.5, 1, 2, 5, 
8, 12 hours 
post-dose 
Xc 
Pre-
dose 
Pre-dose, 1, 2, 4 
and 6 hours after 
start of continuous 
infusion 
Pre-dose 
Pre-dose 
  
  
2 
EOI then 2 
hours after 
EOI 
24 hr post-dose 
 
  
EOI 
  
  
  


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Cycle 
Day 
LMB-100 
PKs (5.1.1)  
Nab-paclitaxel 
PKsa (5.1.2) 
Pharmacogenetic 
studies (5.1.3) 
ADA 
(5.1.2)  
PE mediated 
CLS (Cytokines) 
and serum MPF 
level 
 (5.1.6, 5.1.12) 
CECs, Immune 
Subsets, CTCs 
(5.1.7, 5.1.8, 
5.1.10) 
Immune 
gene 
expression 
(5.1.9) 
Tumor 
Sample 
(5.1.5, 5.1.11) 
2 mL 
K2EDTA 
tube 
4mL in 6 mL 
sodium heparin 
tube 
4-6 mL in purple 
top tube 
2 mL 
K2ED
TA 
tube 
4 mL red SST 
tube 
Two 
7.5 
mL 
Veridex 
CellSave 
& three 8 mL CPT 
citrate tubes 
2.5 mL 
PAXgene 
RNA tube 
NA 
  
3 
  
48 hr post-dose 
  
  
  
24 hrs after EOId 
24 hrs after 
EOId 
  
  
4 
  
72 hr post-dose 
  
  
  
  
  
  


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Cycle 
Day 
LMB-100 
PKs (5.1.1)  
Nab-paclitaxel 
PKsa (5.1.2) 
Pharmacogenetic 
studies (5.1.3) 
ADA 
(5.1.2)  
PE mediated 
CLS (Cytokines) 
and serum MPF 
level 
 (5.1.6, 5.1.12) 
CECs, Immune 
Subsets, CTCs 
(5.1.7, 5.1.8, 
5.1.10) 
Immune 
gene 
expression 
(5.1.9) 
Tumor 
Sample 
(5.1.5, 5.1.11) 
2 mL 
K2EDTA 
tube 
4mL in 6 mL 
sodium heparin 
tube 
4-6 mL in purple 
top tube 
2 mL 
K2ED
TA 
tube 
4 mL red SST 
tube 
Two 
7.5 
mL 
Veridex 
CellSave 
& three 8 mL CPT 
citrate tubes 
2.5 mL 
PAXgene 
RNA tube 
NA 
2 
1 
Pre-dose 
and end of 
loading 
dose  
  
  
Pre-
dose 
Pre-dose 
Pre-dose 
Pre-dose 
  
2 
EOI 
  
  
  
  
  
  
  
3  
(Arm B2 
only) 
 
 
 
 
 
 
 
Xe 
8  
(Arms A1, 
A2, B1) 
  
  
  
  
  
  
  
Xe 
3  
(Arm B2 
only) 
1 
 
Pre-dose 
and end of 
loading 
dose 
 
 
Pre-
dose 
 
 
 
 
2 
EOI 
 
 
 
 
 
 
 
At time of 
Progression 
 
  
  
  
  
X 
X 
  
  
  
Withdrawal 
Visit 
  
  
  
  
X 
X 
  
  
  


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Cycle 
Day 
LMB-100 
PKs (5.1.1)  
Nab-paclitaxel 
PKsa (5.1.2) 
Pharmacogenetic 
studies (5.1.3) 
ADA 
(5.1.2)  
PE mediated 
CLS (Cytokines) 
and serum MPF 
level 
 (5.1.6, 5.1.12) 
CECs, Immune 
Subsets, CTCs 
(5.1.7, 5.1.8, 
5.1.10) 
Immune 
gene 
expression 
(5.1.9) 
Tumor 
Sample 
(5.1.5, 5.1.11) 
2 mL 
K2EDTA 
tube 
4mL in 6 mL 
sodium heparin 
tube 
4-6 mL in purple 
top tube 
2 mL 
K2ED
TA 
tube 
4 mL red SST 
tube 
Two 
7.5 
mL 
Veridex 
CellSave 
& three 8 mL CPT 
citrate tubes 
2.5 mL 
PAXgene 
RNA tube 
NA 
Safety 
Follow-up 
Visit  
  
  
  
  
X 
X 
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ADA =anti-drug antibody; EOI =End of infusion; PK =pharmacokinetic; CTC=circulating tumor cell; CEC=circulating endothelial cell 
a. 
Performed only in subjects receiving nab-paclitaxel (i.e., not performed in single agent lead in) 
b. 
Archival tissue collection or biopsy if no tissue available (mandatory).  
c. 
Collected preferably at baseline, but may be collected at any time during the study. 
d. 
May alternatively be drawn on day prior (at least 2 hours post-EOI) to avoid a weekend draw 
e. 
Optional  
 
 


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5.2.2.2 48-hour continuous infusion 
Timed samples scheduled for within 4 hours after reference point (start of infusion or end of infusion) should be collected within +/- 15 minutes of 
indicted time.  Those collected 4 or more hours after reference point (start of infusion or end of infusion) may be collected within +/- 60 minutes of 
indicated time.  
Cycle 
Day 
LMB-100 PKs  
(5.1.1) 
Nab-paclitaxel PKsa 
(5.1.2) 
Pharmacogenetic 
studies 
(5.1.3) 
ADA  
(5.1.2) 
PE mediated CLS 
(Cytokines) and 
serum MPF level 
(5.1.6, 5.1.12) 
CECs, Immune 
Subsets, 
CTCs 
(5.1.7, 5.1.8, 
5.1.10) 
Immune 
gene 
expression 
(5.1.9) 
Tumor 
Sample 
(5.1.5, 
5.1.11) 
2 mL K2EDTA 
tube 
4mL in 6 mL sodium 
heparin tube 
4-6 mL in purple 
top tube 
2 mL 
K2EDTA 
tube 
4 mL red SST tube 
Two 7.5 mL 
Veridex CellSave 
& three 8 mL CPT 
citrate tubes 
2.5 mL 
PAXgene 
RNA tube 
NA 
Screening 
Screening  
  
 
 
  
  
 
 
Xb 
1 
1 
Pre-dose, End of 
loading dose, 2, 
and 6 hours after 
start of infusion 
pre-infusion, half way 
through loading dose 
(15-min), 2-5min prior 
to end of loading dose 
(25-28min), EOI, and 
0.5, 1, 2, 5, 8, 12, 24, 
48 and 72 hr post dose.   
Xc 
Pre-dose 
Pre-dose, 1, 2, 4 
and 6 hours after 
start of infusion 
Pre-dose 
Pre-dose 
 
 
2 
24 hours after 
start of infusion 
 
 
 
24 hours after start 
of infusion 
 
 
 
 
3 
EOI then 2 hours 
after EOI 
 
 
  
EOI 
 
 
 
 
4 
 
 
 
 
 
24 hrs after EOId 
24 hrs after 
EOId 
 


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Cycle 
Day 
LMB-100 PKs  
(5.1.1) 
Nab-paclitaxel PKsa 
(5.1.2) 
Pharmacogenetic 
studies 
(5.1.3) 
ADA  
(5.1.2) 
PE mediated CLS 
(Cytokines) and 
serum MPF level 
(5.1.6, 5.1.12) 
CECs, Immune 
Subsets, 
CTCs 
(5.1.7, 5.1.8, 
5.1.10) 
Immune 
gene 
expression 
(5.1.9) 
Tumor 
Sample 
(5.1.5, 
5.1.11) 
2 mL K2EDTA 
tube 
4mL in 6 mL sodium 
heparin tube 
4-6 mL in purple 
top tube 
2 mL 
K2EDTA 
tube 
4 mL red SST tube 
Two 7.5 mL 
Veridex CellSave 
& three 8 mL CPT 
citrate tubes 
2.5 mL 
PAXgene 
RNA tube 
NA 
2 
1 
Pre-dose, end of 
loading dose and 
2 hours after 
start of infusion 
 
 
Pre-dose 
Pre-dose 
Pre-dose 
Pre-dose 
 
2 
24 hours after 
start of infusion 
 
 
 
 
 
 
 
3 
EOI 
 
 
 
 
 
 
 
8 
 
 
 
 
 
 
 
Xe 
At time of 
Progression 
 
 
 
 
X 
X 
 
 
 
Withdrawal 
Visit 
 
 
 
 
X 
X 
 
 
 
Safety 
Follow-up 
Visit  
 
 
 
 
X 
X 
 
 
 
ADA =anti-drug antibody; EOI =End of infusion; PK =pharmacokinetic; CTC=circulating tumor cell; CEC=circulating endothelial cell 
a. 
Performed only in subjects receiving nab-paclitaxel (i.e., not performed in single agent lead in) 
b. 
Archival tissue collection or biopsy if no tissue available (mandatory).  
c. 
Collected preferably at baseline, but may be collected at any time during the study. 
d. 
May alternatively be drawn on day prior (at least 2 hours post-EOI) to avoid a weekend draw 
e. 
Optional 


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5.3 
SAMPLE STORAGE, TRACKING AND DISPOSITION 
Samples will be ordered in CRIS and tracked through a Clinical Trial Data Management system. 
Should a CRIS screen not be available, the CRIS downtime procedures will be followed.  Samples 
will not be sent outside NIH without IRB notification and an executed MTA.  
5.3.1 Clinical Pharmacology Program 
Upon arrival in the Clinical Pharmacology Program (CPP), OCD, CCR, NCI, all samples are 
barcoded, with data entered and stored in Patient Sample Data Management System (PSDMS), 
also known as Labrador, the system utilized by the CPP. This is a secure program, with access to 
the PSDMS system limited to defined CPP personnel, who are issued individual user accounts. 
PSDMS creates a unique barcode ID for every sample and sample box, which cannot be traced 
back to patients without PSDMS access. The data recorded for each sample includes the patient 
ID, name, trial name/protocol number, time drawn, cycle, time point, dose, material type, as well 
as box and freezer location. There are patient demographics that can be obtained to correlate with 
the samples through PSDMS. For each sample, there are notes associated with processing method 
(delay in sample processing, storage conditions on the ward, etc.) 
Barcoded samples are stored in barcoded boxes in a locked freezer at either -20°C or -80°C 
according to stability requirements. These freezers are located onsite in the CPP and offsite at NCI 
Frederick Central Repository Services in Frederick, MD. Samples will be stored until requested 
by the researcher assigned to the protocol. All requests are monitored and tracked in PSDMS. All 
researchers are required to sign a form stating that the samples are only to be used for research 
purposes associated with this trial (as per IRB approved protocol) and that any unused samples 
must be returned to the CPP. 
Following completion of this study, samples will remain in storage as detailed above. Access to 
these samples will only be granted following IRB approval of an additional protocol, granting the 
rights to use the material. 
5.3.2 Leidos Biomedical, Inc. Lab 
Blood and tissue collected during the course of this study will follow storage, handling and labeling 
procedures to ensure that security, confidentiality and sample integrity are maintained. All samples 
(blood or tissue) are tracked by distinct identification labels that include a unique patient identifier 
and date of specimen collection. Thus, samples will be de-identified of personal data, with access 
to personal data restricted to the study investigators.   
All cryopreserved samples are tracked for freezer location and storage criteria. All Samples are 
stored in a locked freezer at -70qC according to stability requirements.  These freezers are located 
offsite at NCI-Frederick, at the Leidos Biomedical, Inc. lab in Frederick, MD.  Samples will be 
stored until requested by a researcher named on the protocol.  All use and requests for use will be 
recorded by the Leidos Biomedical, Inc. Lab. Any unused samples must be returned. 
Some samples as indicated below may be stored in monitored freezers/refrigerators in the 
investigator’s laboratory at specified temperatures with alarm systems in place.  


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At the termination of this protocol, samples will remain in storage as detailed above.  Access to 
these samples will only be granted following IRB approval of an additional protocol or an 
exemption from IRB approval, granting the rights to use the material.  If specimens are to be 
discarded at any point, they will be disposed of in accordance with the environmental protection 
laws, regulations and guidelines of the Federal Government and the State of Maryland. 
If, at any time, a patient withdraws from the study and does not wish for their existing samples to 
be utilized, the individual must provide a written request. Following receipt of this request, the 
samples will be destroyed (or returned to the patient, if so requested), and reported as such to the 
IRB.    
5.3.3 Laboratory of Jane Trepel 
Samples will be processed immediately by the Trepel laboratory.  Biospecimens will be collected 
and processed using validated SOPs that will ensure both specimen quality and patient 
confidentiality. Using a computerized inventory system and a backup hardcopy process, all 
specimen collection and processing steps will be documented and the specific location of each 
specimen will be tracked. Each new specimen collected will be assigned a unique barcode 
identifier that can be linked to the original specimen collected and other relevant information 
within the inventory system.  Specimen labels will indicate: protocol number, order in which the 
patient enrolled on the trial, type of sample, collection time, and total volume collected, as 
appropriate.  The inventory process contains other security provisions sufficient to safeguard 
patient privacy and confidentiality. Access to the inventory system and associated documents will 
be restricted to appropriate individuals. Requests to use specimens stored in the repository must 
be approved. SOPs ensure that any changes in informed consent made by a patient and relayed to 
the PI will be reflected in the inventory system to ensure that specimens are destroyed as 
appropriate. All laboratory personnel will be trained to adhere to SOPs and will be monitored for 
high-quality performance. 
5.3.4 Protocol Completion/Sample Destruction 
All specimens obtained in the protocol are used as defined in the protocol. Any specimens 
remaining at the completion of the protocol will be stored in the conditions described above. The 
study will remain open as long as sample or data analysis continues. Samples from consenting 
subjects will be stored until they are no longer of scientific value or until a subject withdraws 
consent for their continued use, at which time they will be destroyed. Once primary research 
objectives for the protocol are achieved, intramural researchers can request access to remaining 
samples, provided they have an IRB-approved protocol and participant consent or an exemption 
from OHSRP.  
The PI will report any loss or destruction of samples to the NIH Intramural IRB as soon as he/she 
is made aware of such loss. The PI will report destroyed samples to the IRB if samples become 
unsalvageable because of environmental factors such as a broken freezer or lack of dry ice in a 
shipping container, or if a participant withdraws consent. Samples will also be reported as lost if 
they are lost in transit between facilities or misplaced by a researcher. Freezer problems, lost 
samples, or other problems associated with samples will also be reported to the IRB, the NCI 
Clinical Director, and the office of the CCR, NCI. 
 


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5.4 
SAMPLES FOR GENETIC ANALYSIS 
Pharmacogenetic studies will be performed on this protocol as described in section 5.1.3 and 
samples will be stored and secured as described in section 5.3.1. Because the analysis is limited to 
genes that play a role in drug metabolism, none of which are currently associated with disease 
causing genes, incidental findings will not be returned on this study. 
6 
DATA COLLECTION AND EVALUATION  
6.1 
DATA COLLECTION 
Study data will be recorded and stored in the C3D and Labmatrix databases. The PI will be 
responsible for overseeing entry of data into an in-house password protected electronic system and 
ensuring data accuracy, consistency and timeliness. The principal investigator, associate 
investigators/research nurses and/or a contracted data manager will assist with the data 
management efforts. All data obtained during the conduct of the protocol will be kept in secure 
network drives or in approved alternative sites that comply with NIH security standards. Primary 
and final analyzed data will have identifiers so that research data can be attributed to an individual 
human subject participant. 
All adverse events, including clinically significant abnormal findings on laboratory evaluations, 
regardless of severity, will be followed until return to baseline or stabilization of event. Patients 
will be followed for adverse events for 30 days after removal from study treatment or until off-
study, whichever comes first. Adverse events occurring more than 30 days after the last dose of 
study therapy are only required to be recorded only if they are considered to be serious and related 
to the investigational agent/intervention. 
An abnormal laboratory value will be recorded in the database as an AE only if the laboratory 
abnormality is characterized by any of the following: 
x 
Results in discontinuation from the study 
x 
Is associated with clinical signs or symptoms  
x 
Requires treatment or any other therapeutic intervention 
x 
Is associated with death or another serious adverse event, including hospitalization.  
x 
Is judged by the Investigator to be of significant clinical impact 
x 
If any abnormal laboratory result is considered clinically significant, the investigator will 
provide details about the action taken with respect to the test drug and about the patient’s 
outcome. 
End of study procedures: Data will be stored according to HHS, FDA regulations and NIH 
Intramural Records Retention Schedule as applicable.  
Loss or destruction of data: Should we become aware that a major breach in our plan to protect 
subject confidentiality and trial data has occurred, the IRB will be notified.  


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6.2 
DATA SHARING PLANS 
6.2.1 Human Data Sharing Plan 
What data will be shared? 
I will share human data generated in this research for future research as follows: 
_X_ Coded, linked data in an NIH-funded or approved public repository.   
_X_ Coded, linked data in BTRIS 
_X_ Identified or coded, linked data with approved outside collaborators under appropriate 
agreements. 
 
How and where will the data be shared?  
Data will be shared through: 
_X_ An NIH-funded or approved public repository.  Insert name or names:_clinicaltrials.gov__. 
_X_ BTRIS (automatic for activities in the Clinical Center) 
_X_ Approved outside collaborators under appropriate individual agreements. 
_X_ Publication and/or public presentations. 
 
When will the data be shared? 
_X_ Before publication. 
_X_ At the time of publication or shortly thereafter. 
6.2.2 Genomic Data Sharing Plan 
The SNP arrays utilized on this study (DMET chip) cover approximately 2000 genes, which are 
not defined as large scale genomic data under the GDS policy. 
6.3 
RESPONSE CRITERIA 
For the purposes of this study, participants should be re-evaluated following cycle 2, then every 6 
weeks (+/- 2 weeks) until disease progression.  In addition to a baseline scan, confirmatory scans 
should also be obtained no less than 4 weeks following initial documentation of objective response. 
Response and progression will be assessed by the investigator on the basis of physical 
examinations, computed tomography (CT) or Magnetic Resonance (MR) scans, and potentially 
other modalities according to standard of care, using the international criteria proposed by the 
revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).[43]  
Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the 
shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. For 
patients with pleural mesothelioma, modified RECIST criteria will be used to assess response. 


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ORR, DCR and PFS measured according to these criteria will be reported as exploratory 
objectives. 
6.3.1 Definitions 
Evaluable for toxicity:  All participants will be evaluable for toxicity from the time of their first 
treatment with LMB-100. 
The dose determining population will consist of all participants evaluable for DLT. Participants 
are evaluable for DLT if they are evaluable for toxicity and discontinued earlier due to DLT or 
completed the DLT observation period the first cycle during phase I and have undergone safety 
evaluations. 
Evaluable for pharmacokinetic analysis: All participants that are evaluable for toxicity will be 
included in the PK analysis population. Participants will be excluded from the PK analysis 
population if they significantly violate the inclusion or exclusion criteria, deviate from the protocol, 
or if data are unavailable or incomplete which may influence the PK analysis. Excluded cases will 
be documented with the reason for exclusion. 
Evaluable for objective response: Only those participants who have measurable disease present at 
baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will 
be considered evaluable for response.  These participants will have their response classified 
according to the definitions stated below.  (Note:  Participants who exhibit objective disease 
progression prior to the end of cycle 1 will also be considered evaluable.) 
Evaluable Non-Target Disease Response:  Participants who have lesions present at baseline that 
are evaluable but do not meet the definitions of measurable disease, have received at least one 
cycle of therapy, and have had their disease re-evaluated will be considered evaluable for non-
target disease.  The response assessment is based on the presence, absence, or unequivocal 
progression of the lesions.  
6.3.2 All Diseases except pleural mesothelioma 
6.3.2.1 Disease Parameters 
Measurable disease:  Measurable lesions are defined as those that can be accurately measured in 
at least one dimension (longest diameter to be recorded) as: 
x By chest x-ray: >20 mm;  
x By CT scan:  
o Scan slice thickness 5 mm or under: as >10 mm 
o Scan slice thickness >5 mm: double the slice thickness  
x With calipers on clinical exam: >10 mm.   
All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). 
Malignant lymph nodes.  To be considered pathologically enlarged and measurable, a lymph node 
must be >15 mm in short axis when assessed by CT scan (CT scan slice thickness recommended 
to be no greater than 5 mm).  At baseline and in follow-up, only the short axis will be measured 
and followed. 


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Non-measurable disease.  All other lesions (or sites of disease), including small lesions (longest 
diameter <10 mm or pathological lymph nodes with ≥10 to <15 mm short axis), are considered 
non-measurable disease.  Bone lesions, leptomeningeal disease, ascites, pleural/pericardial 
effusions, lymphangitis cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not 
followed by CT or MRI), are considered as non-measurable. 
Note:  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. 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesions, if 
they meet the definition of measurability described above. However, if non-cystic lesions are 
present in the same participant, these are preferred for selection as target lesions. 
Target lesions.  All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in 
total, representative of all involved organs, should be identified as target lesions and recorded and 
measured at baseline.  Target lesions should be selected on the basis of their size (lesions with the 
longest diameter), be representative of all involved organs, but in addition should be those that 
lend themselves to reproducible repeated measurements.  It may be the case that, on occasion, the 
largest lesion does not lend itself to reproducible measurement in which circumstance the next 
largest lesion which can be measured reproducibly should be selected.  A sum of the diameters 
(longest for non-nodal lesions, short axis for nodal lesions) for all target lesions will be calculated 
and reported as the baseline sum diameters.  If lymph nodes are to be included in the sum, then 
only the short axis is added into the sum.  The baseline sum diameters will be used as reference to 
further characterize any objective tumor regression in the measurable dimension of the disease. 
Non-target lesions.  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 and should also be 
recorded at baseline.  Measurements of these lesions are not required, but the presence, absence, 
or in rare cases unequivocal progression of each should be noted throughout follow-up.  
6.3.2.2 Methods for Evaluation of Measurable Disease 
All measurements should be taken and recorded in metric notation using a ruler or calipers.  All 
baseline evaluations should be performed as closely as possible to the beginning of treatment and 
never more than 4 weeks before the beginning of the treatment. 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is 
preferred to evaluation by clinical examination unless the lesion(s) being followed cannot be 
imaged but are assessable by clinical exam. 
Clinical lesions:  Clinical lesions will only be considered measurable when they are superficial 
(e.g., skin nodules and palpable lymph nodes) and t10 mm diameter as assessed using calipers 
(e.g., skin nodules).  In the case of skin lesions, documentation by color photography, including a 
ruler to estimate the size of the lesion, is recommended.  
Chest x-ray:  Lesions on chest x-ray are acceptable as measurable lesions when they are clearly 
defined and surrounded by aerated lung.  However, CT is preferable.  


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Conventional CT and MRI:  This guideline has defined measurability of lesions on CT scan based 
on the assumption that CT slice thickness is 5 mm or less.  If CT scans have slice thickness greater 
than 5 mm, the minimum size for a measurable lesion should be twice the slice thickness.  MRI is 
also acceptable in certain situations (e.g. for body scans).   
Use of MRI remains a complex issue.  MRI has excellent contrast, spatial, and temporal resolution; 
however, there are many image acquisition variables involved in MRI, which greatly impact image 
quality, lesion conspicuity, and measurement.  Furthermore, the availability of MRI is variable 
globally.  As with CT, if an MRI is performed, the technical specifications of the scanning 
sequences used should be optimized for the evaluation of the type and site of disease.  Furthermore, 
as with CT, the modality used at follow-up should be the same as was used at baseline and the 
lesions should be measured/assessed on the same pulse sequence.  It is beyond the scope of the 
RECIST guidelines to prescribe specific MRI pulse sequence parameters for all scanners, body 
parts, and diseases.  Ideally, the same type of scanner should be used and the image acquisition 
protocol should be followed as closely as possible to prior scans.  Body scans should be performed 
with breath-hold scanning techniques, if possible. 
PET-CT:  At present, the low dose or attenuation correction CT portion of a combined 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 (with IV and oral contrast), then the CT portion of the PET-CT can be used for 
RECIST measurements and can be used interchangeably with conventional CT in accurately 
measuring cancer lesions over time.  Note, however, that the PET portion of the CT introduces 
additional data which may bias an investigator if it is not routinely or serially performed.   
Ultrasound:  Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement.  Ultrasound examinations cannot be reproduced in their entirety for 
independent review at a later date and, because they are operator dependent, it cannot be 
guaranteed that the same technique and measurements will be taken from one assessment to the 
next.  If new lesions are identified by ultrasound in the course of the study, confirmation by CT or 
MRI is advised.  If there is concern about radiation exposure at CT, MRI may be used instead of 
CT in selected instances. 
Endoscopy, Laparoscopy:  The utilization of these techniques for objective tumor evaluation is not 
advised.  However, such techniques may be useful to confirm complete pathological response 
when biopsies are obtained or to determine relapse in trials where recurrence following complete 
response (CR) or surgical resection is an endpoint. 
Tumor markers:  Tumor markers alone cannot be used to assess response.  If markers are initially 
above the upper normal limit, they must normalize for a patient to be considered in complete 
clinical response.  Specific guidelines for both CA-125 response (in recurrent ovarian cancer) and 
PSA response (in recurrent prostate cancer) have been published.[44-46]  In addition, the 
Gynecologic Cancer Intergroup has developed CA-125 progression criteria which are to be 
integrated with objective tumor assessment for use in first-line trials in ovarian cancer.[47] 
Cytology, Histology:  These techniques can be used to differentiate between partial responses (PR) 
and complete responses (CR) in rare cases (e.g., residual lesions in tumor types, such as germ cell 
tumors, where known residual benign tumors can remain). 


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The cytological confirmation of the neoplastic origin of any effusion that appears or worsens 
during treatment when the measurable tumor has met criteria for response or stable disease is 
mandatory to differentiate between response or stable disease (an effusion may be a side effect of 
the treatment) and progressive disease. 
FDG-PET:  While FDG-PET response assessments need additional study, it is sometimes 
reasonable to incorporate the use of FDG-PET scanning to complement CT scanning in assessment 
of progression (particularly possible 'new' disease).  New lesions on the basis of FDG-PET imaging 
can be identified according to the following algorithm:  
a. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD 
based on a new lesion. 
b. No FDG-PET at baseline and a positive FDG-PET at follow-up:  If the positive FDG-
PET at follow-up corresponds to a new site of disease confirmed by CT, this is PD.  If 
the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT  scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial abnormal FDG-
PET scan).  If the positive FDG-PET at follow-up corresponds to a pre-existing site of 
disease on CT that is not progressing on the basis of the anatomic images, this is not 
PD. 
c. FDG-PET may be used to upgrade a response to a CR in a manner similar to a biopsy 
in cases where a residual radiographic abnormality is thought to represent fibrosis or 
scarring.  The use of FDG-PET in this circumstance should be prospectively described 
in the protocol and supported by disease-specific medical literature for the indication.  
However, it must be acknowledged that both approaches may lead to false positive CR 
due to limitations of FDG-PET and biopsy resolution/sensitivity. 
Note:  A ‘positive’ FDG-PET scan lesion means one which is FDG avid with an uptake greater 
than twice that of the surrounding tissue on the attenuation corrected image. 
6.3.2.3 RECIST 1.1 Criteria 
6.3.2.3.1 Evaluation of Target Lesions 
Complete Response (CR): Disappearance of all target lesions.  Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm. 
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking 
as reference the baseline sum of diameters. 
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest 
on study).  In addition to the relative increase of 20%, the sum must also demonstrate an absolute 
increase of at least 5 mm.  (Note:  the appearance of one or more new lesions is also considered 
progressions). 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum of diameters while on study. 
6.3.2.3.2 Evaluation of Non-Target Lesions 


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Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor 
marker level.  All lymph nodes must be non-pathological in size (<10 mm short axis). 
Note:  If tumor markers are initially above the upper normal limit, they must normalize for a 
participant to be considered in complete clinical response. 
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits. 
Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression 
of existing non-target lesions.  Unequivocal progression should not normally trump target lesion 
status.  It must be representative of overall disease status change, not a single lesion increase. 
Although a clear progression of “non-target” lesions only is exceptional, the opinion of the treating 
physician should prevail in such circumstances, and the progression status should be confirmed at 
a later time by the review panel (or Principal Investigator). 
6.3.2.3.3 Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until disease 
progression/recurrence (taking as reference for progressive disease the smallest measurements 
recorded since the treatment started).  The participant's best response assignment will depend on 
the achievement of both measurement and confirmation criteria. 
For Participants with Measurable Disease (i.e., Target Disease) 
Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response when 
Confirmation is Required* 
CR 
CR 
No 
CR 
>4 wks. Confirmation** 
CR 
Non-
CR/Non-PD 
No 
PR 
>4 wks. Confirmation** 
CR 
Not 
evaluated 
No 
PR 
PR 
Non-
CR/Non-
PD/not 
evaluated 
No 
PR 
SD 
Non-
CR/Non-
PD/not 
evaluated 
No 
SD 
Documented at least once >4 
wks. from baseline** 
PD 
Any 
Yes or 
No 
PD 
no prior SD, PR or CR 
Any 
PD*** 
Yes or 
No 
PD 
Any 
Any 
Yes 
PD 


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Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response when 
Confirmation is Required* 
* 
See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
** 
Only for non-randomized trials with response as primary endpoint. 
*** 
In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as 
disease progression. 
Note: 
Participants with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as “symptomatic 
deterioration.”  Every effort should be made to document the objective progression even after 
discontinuation of treatment. 
For Participants with Non-Measurable Disease (i.e., Non-Target Disease) 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
*  ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly used as 
an endpoint for assessment of efficacy in some trials so to assign this category when no lesions can be 
measured is not advised 
6.3.3 Pleural Mesothelioma 
Malignant pleural mesothelioma (MPM) lesions are difficult to measure reliably.[48] Therefore modified 
criteria were defined in 2004 adjusting target lesion measurements to the specific needs of this disease. 
6.3.3.1 Modified RECIST Criteria for MPM 
Target lesion:  
Measurable at baseline and defined as tumor thickness measurements perpendicular to the chest 
wall or mediastinum in two positions at three separate levels on transverse cuts of CT scan. The 
sum of those 6 measurements define a pleural unidimensional measure. For reproducibility of 
lesion identification in follow up scans, cuts were taken at least 1 cm apart and close to anatomical 
landmarks in the thorax. Reassessments should be done at same position at the same level and by 
the same reader. Nodal, subcutaneous, and other measurable lesion were measured as per RECIST 
criteria. All unidimensional measurements were added to obtain total tumor measurement. 
Evaluation of target lesions  
x 
Complete Response (CR): Disappearance of all target lesions with no evidence of tumor 
elsewhere.  
x 
Partial Response (PR): At least a 30% decrease in the total tumor measurement  


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x 
Confirmed response (PR and CR): require a repeat scan at least 4 weeks apart  
x 
Progressive Disease (PD): At least a 20% increase in the total tumor measurement, taking 
as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). (Note: the appearance of one or more new lesions is also considered 
progression).  
x 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase 
to qualify for PD, taking as reference the smallest sum diameters while on study.  
6.3.3.2 Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until disease 
progression/recurrence (taking as reference for progressive disease the smallest measurements 
recorded since the treatment started).  The patient's best response assignment will depend on the 
achievement of both measurement and confirmation criteria. 
Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best 
Response 
for 
this 
Category Also Requires: 
CR 
CR 
No 
CR 
>4 wks. confirmation 
CR 
Non-CR/Non-
PD 
No 
PR 
 
>4 wks. confirmation 
PR 
Non-PD 
No 
PR 
SD 
Non-PD 
No 
SD 
documented at least once >4 
wks. from baseline 
PD 
Any 
Yes or No 
PD 
 
no prior SD, PR or CR 
Any 
PD* 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
* In exceptional circumstances, unequivocal progression in non-target lesions may be accepted 
as disease progression. 
 
Note: Patients with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as 
“symptomatic deterioration”.  Every effort should be made to document the objective 
progression even after discontinuation of treatment. 
 
               In some circumstances it may be difficult to distinguish residual disease from normal 
tissue. When the evaluation of complete response depends on this determination, it is 
recommended that the residual lesion be investigated (fine needle aspirate/biopsy) to 
confirm the complete response status. 
 
 


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6.3.4 Duration of Response 
Duration of overall response:  The duration of overall response is measured from the time 
measurement criteria are met for CR or PR (whichever is first recorded) until the first date that 
recurrent or progressive disease is objectively documented (taking as reference for progressive 
disease the smallest measurements recorded since the treatment started). 
The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that progressive disease is objectively documented. 
Duration of stable disease:  Stable disease is measured from the start of the treatment until the 
criteria for progression are met, taking as reference the smallest measurements recorded since the 
treatment started, including the baseline measurements.  
6.3.5 Progression-Free Survival 
Progression free survival (PFS) is defined as the duration of time from start of treatment to time 
of progression or death, whichever occurs first. 
6.3.6 Objective Response Rate 
Objective response rate (ORR) is defined as the proportion of participants with partial response or 
complete response. 
6.3.7 Disease Control Rate 
Disease control rate (DCR) is defined as the proportion of participants with stable disease, partial 
response or complete response 
6.4 
TOXICITY CRITERIA 
The following adverse event management guidelines are intended to ensure the safety of each 
participant while on the study.  The descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE 
reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0. 
A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40).  
7 
SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING 
PLAN 
7.1 
DEFINITIONS 
7.1.1 Adverse Event 
Any untoward medical occurrence in a human subject, including any abnormal sign (for example, 
abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with 
the subject’s participation in research, whether or not considered related to the subject’s 
participation in the research.  


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7.1.2 Suspected adverse reaction 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility 
that the drug caused the adverse event. For the purposes of IND safety reporting, ‘reasonable 
possibility’ means there is evidence to suggest a causal relationship between the drug and the 
adverse event. A suspected adverse reaction implies a lesser degree of certainty about causality 
than adverse reaction, which means any adverse event caused by a drug. 
7.1.3 Unexpected adverse reaction 
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in the 
investigator brochure or is not listed at the specificity or severity that has been observed; or, if an 
investigator brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application. "Unexpected” 
also refers to adverse events or suspected adverse reactions that are mentioned in the investigator 
brochure as occurring with a class of drugs or as anticipated from the pharmacological properties 
of the drug, but are not specifically mentioned as occurring with the particular drug under 
investigation. 
7.1.4 Serious  
An Unanticipated Problem or Protocol Deviation is serious if it meets the definition of a Serious 
Adverse Event or if it compromises the safety, welfare or rights of subjects or others. 
7.1.5 Serious Adverse Event 
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator, it results in any of the following: 
x 
Death, 
x 
A life-threatening adverse drug experience 
x 
Inpatient hospitalization or prolongation of existing hospitalizationPersistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions 
x 
A congenital anomaly/birth defect. 
x 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the participant or subject and may 
require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. 
7.1.6 Disability 
 A substantial disruption of a person’s ability to conduct normal life functions. 
7.1.7 Life-threatening adverse drug experience 
Any adverse event or suspected adverse reaction that places the participant or subject, in the view 
of the investigator or sponsor, at immediate risk of death from the reaction as it occurred, i.e., it 
does not include a reaction that had it occurred in a more severe form, might have caused death. 


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7.1.8 Protocol Deviation (NIH Definition) 
Any change, divergence, or departure from the IRB-approved research protocol.   
7.1.9 Non-compliance (NIH Definition) 
The failure to comply with applicable NIH Human Research Protections Program (HRPP) policies, 
IRB requirements, or regulatory requirements for the protection of human research subjects. 
7.1.10 Unanticipated Problem 
Any incident, experience, or outcome that: 
x Is unexpected in terms of nature, severity, or frequency in relation to  
(a) the research risks that are described in the IRB-approved research protocol and 
informed consent document; Investigator’s Brochure or other study documents, and 
(b) the characteristics of the subject population being studied; AND 
x Is related or possibly related to participation in the research; AND 
x Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
7.2 
NIH INTRAMURAL IRB AND CLINICAL DIRECTOR (CD) REPORTING 
7.2.1 NIH Intramural IRB and NCI CD Expedited Reporting of Unanticipated Problems and 
Deaths 
The Protocol PI will report on the NIH Problem Form to the NIH Intramural IRB and NCI Clinical 
Director: 
x All deaths, except deaths due to progressive disease  
x All Protocol Deviations 
x All Unanticipated Problems 
x All non-compliance 
Reports must be received within 7 days of PI awareness via iRIS. 
7.2.2 NIH Intramural IRB Requirements for PI Reporting at Continuing Review 
The protocol PI will report to the NIH Intramural IRB:  
1. A summary of all protocol deviations in a tabular format to include the date the deviation 
occurred, a brief description of the deviation and any corrective action. 
2. A summary of any instances of non-compliance 
3. A tabular summary of the following adverse events: 


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x All Grade 2 unexpected events that are possibly, probably or definitely related to the 
research;  
x All Grade 3 and 4 events that are possibly, probably or definitely related to the research;  
x All Grade 5 events regardless of attribution;  
x All Serious Events regardless of attribution.  
NOTE: Grade 1 events are not required to be reported.  
7.2.3 NIH Intramural IRB Reporting of IND Safety Reports 
Only IND Safety Reports that meet the definition of an unanticipated problem will need to be 
reported to the NIH Intramural IRB. 
7.3 
IND SPONSOR REPORTING CRITERIA  
Starting from the initiation of study therapy and continuing through  the first 30 days after the 
subject receives the last administration of the investigational agent/intervention, the investigator 
must immediately report to the sponsor, using the mandatory MedWatch form 3500a or equivalent, 
any serious adverse event, whether or not considered drug related, including those listed in the 
protocol or investigator brochure and must include an assessment of whether there is a reasonable 
possibility that the drug caused the event. For events that occur more than 30 days after the last 
administration of investigational agent/intervention, only report serious adverse events  that have 
an attribution of at least possibly related to the agent/intervention. 
Required timing for reporting per the above guideline: 
 
x Deaths (except death due to progressive disease) must be reported via email within 
24 hours.  A complete report must be submitted within one business day.  
x Other serious adverse events as well as deaths due to progressive disease must be 
reported within one business day 
Events will be submitted to the Center for Cancer Research (CCR) at: CCRsafety@mail.nih.gov 
and to the CCR PI and study coordinator. 
7.3.1 Reporting Pregnancy  
7.3.1.1 Maternal exposure 
If a patient becomes pregnant during the course of the study, the study treatment should be 
discontinued immediately and the pregnancy reported to the Sponsor. The potential risk of 
exposure of the fetus to the investigational agent(s) or chemotherapy agents (s) should be 
documented in box B5 of the MedWatch form “Describe Event or Problem”. 
Pregnancy itself is not regarded as an SAE. However, as patients who become pregnant on study 
risk intrauterine exposure of the fetus to agents which may be teratogenic, the CCR is requesting 
that pregnancy should be reported in an expedited manner as Grade 3 “Pregnancy, puerperium 
and perinatal conditions - Other (pregnancy)” under the Pregnancy, puerperium and perinatal 
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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. 
If any pregnancy occurs in the course of the study, then the investigator should inform the Sponsor 
within 1 day, i.e., immediately, but no later than 24 hours of when he or she becomes aware of 
it. 
The designated Sponsor representative will work with the investigator to ensure that all relevant 
information is provided to the Sponsor 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. 
7.3.1.2 Paternal exposure 
Male patients should refrain from fathering a child or donating sperm during the study and for 3 
months after the last dose of LMB-100 or nab-paclitaxel. 
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 3 months after the last dose 
should, if possible, be followed up and documented. 
7.4 
DATA AND SAFETY MONITORING PLAN 
7.4.1 Principal Investigator/Research Team  
The clinical research team will meet on a regular basis when participants are being actively treated 
on the trial to discuss each participant. Decisions about dose level enrollment and dose escalation 
if applicable will be made based on the toxicity data from prior participants.  
All data will be collected in a timely manner and reviewed by the principal investigator or a lead 
associate investigator. Adverse events will be reported as required above. Any safety concerns, 
new information that might affect either the ethical and or scientific conduct of the trial, or protocol 
deviations will be immediately reported to the IRB using iRIS.  
The principal investigator will review adverse event and response data on each participant to 
ensure safety and data accuracy. The principal investigator will personally conduct or supervise 
the investigation and provide appropriate delegation of responsibilities to other members of the 
research staff.  
7.4.2 Sponsor Monitoring Plan 
As a sponsor for clinical trials, FDA regulations require the CCR to maintain a monitoring 
program. The CCR’s program allows for confirmation of: study data, specifically data that could 
affect the interpretation of primary study endpoints; adherence to the protocol, regulations, and 
SOPs; and human subjects protection. This is done through independent verification of study 
data with source documentation focusing on: 
x Informed consent process 
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x Drug administration and accountability 
x Adverse events monitoring 
x Response assessment. 
The monitoring program also extends to multi-site research when the CCR is the coordinating 
center. 
This trial will be monitored by personnel employed by an NCI contractor. Monitors are qualified 
by training and experience to monitor the progress of clinical trials. Personnel monitoring this 
study will not be affiliated in any way with the trial conduct. Safety Monitoring Committee (SMC) 
7.4.3 Safety Monitoring Committee 
This protocol will require oversight from the Safety Monitoring Committee (SMC).  Initial review 
will occur as soon as possible after the annual NIH Intramural IRB continuing review date.   
Subsequently, each protocol will be reviewed as close to annually as the quarterly meeting 
schedule permits or more frequently as may be required by the SMC. For initial and subsequent 
reviews, protocols will not be reviewed if there is no accrual within the review period. Written 
outcome letters will be generated in response to the monitoring activities and submitted to the 
Principal investigator and Clinical Director or Deputy Clinical Director, CCR, NCI. 
8 
STATISTICAL CONSIDERATIONS   
8.1 
PRIMARY ENDPOINTS 
The primary objectives of this trial are to: 
1) determine the MTD of LMB-100 in combination with chemotherapy (NAB-paclitaxel) in 
participants with advanced pancreatic cancer both as a short infusion and as a continuous 
infusion 
2) determine the response rate of the combination as a short infusion 
8.1.1 Part A 
Arm A1 - Phase I. Part A begins with a two dose level escalation using a 3 + 3 design with LMB-
100 potentially evaluated at 100, and 140 mcg/kg in combination with chemotherapy. A lower 
dose of 65 mcg/kg may also be evaluated. If both intended dose levels are explored and each 
requires up to 6 participants, then up to 12 participants may be required for the phase I portion of 
the trial.  Note:  Subjects enrolled prior to Amendment C (n=3) in which the maximum number of 
cycles was reduced, are included in the MTD evaluation as they have received at least 1 cycle of 
LMB-100. 
After the enrollment of patients to the first 2 dose levels the pharmacokinetic and anti-drug 
antibody level (ADA) data will be analyzed before enrolling new patients.  Dr. William Figg, who 
has expertise in pharmacokinetics, will, in conjunction with the NCI CCR leadership 
committee analyze the data.  Since the thresholds for ADA and its influence on pharmacokinetics 
are unclear, pre-specified criteria for making changes to the protocol cannot be established at this 
time.  The objective of the assessment will be to make recommendations as to whether a 
therapeutic threshold has been reached and what, if any adjustments should be made with regard 
to the eligibility criteria and/or study plan. 


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Arm A2 -Phase II portion of Part A. In Arm A2 we will evaluate the combination identified as 
being the MTD from Arm A1. As of 5/1/18, this is anticipated to be at dose level -1.  If dose level 
-1 is not found to be same during Arm A1, we will not proceed to Arm A2.  
If Arm A2 does proceed, since the participants to be treated on the phase II portion will have the 
same eligibility criteria as those on phase I, the 6 participants treated at 65 mcg/kg (the anticipated 
RP2D from Arm A1) will be the 6 initial participants treated on the first stage of the phase II 
cohort. Based upon results from two small trials of NAB-paclitaxel treatment beyond the first-line 
setting, the response rate of participants with advanced pancreatic cancer to NAB-paclitaxel is at 
most 5%.[49, 50]  It would be desirable if this were improved by 15-20% or more. As such, the goal 
would be to determine if using the combination would rule out a 5% response rate to target a rate 
of 25%. The trial will be conducted using a Simon Minimax two-stage phase II trial design[51] in 
order to rule out an unacceptably low PR+CR rate of 5% (p0 = 0.05) in favor of an improved 
response rate of  25% (p1 = 0.25). With α = 0.10 (probability of accepting a poor treatment = 0.10) 
and β = 0.10 (probability of rejecting a good treatment = 0.10). This first stage will enroll 13 
evaluable participants, and if 0 of the 13 have a clinical response, then no further participants will 
be accrued. If 1or more of the first 13 participants has a response, then accrual would continue 
until a total of 20 evaluable participants have been enrolled. As it may take up to several months 
to determine if a participant has experienced a response, a temporary pause in the accrual may be 
necessary to ensure that enrollment to the second stage is warranted. If there are 1 to 2 participants 
with a response out of 20 participants, this would be an uninterestingly low response rate. If there 
were 3 or more of 20 (15%) who experienced a response, this would be sufficiently interesting to 
warrant further study in later trials. Under the null hypothesis (5% response rate), the probability 
of early termination is 51%. 
8.1.2 Part B:  
Arm B1 -Phase I, Continuous Infusion Single Agent Lead-In. While patients who are eligible 
for enrollment into Part A are being treated on Part A, patients who have pancreatic cancer who 
do not meet eligibility criteria for nab-paclitaxel and patients with other MSLN-expressing solid 
tumors will be enrolled onto Part B Single Agent Lead-in. This portion of the trial has dose finding 
using a 3 + 3 design with LMB-100 alone as a continuous infusion, potentially evaluated at doses 
of 65, 100, 140 and 200 mcg/kg/day over 24, 24 *2, 48, 72 and 96 hours using a flexible escalation 
scheme. This will establish the single agent MTD for continuous infusion. Enrollment in this arm 
has been capped at a maximum of 30 participants being treated.  If each dose level requires all 6 
participants, then five dose levels may be examined.    
After the first 3 patients were enrolled, the pharmacokinetic data were  analyzed before enrolling 
new patients.  Dr. William Figg, who has expertise in pharmacokinetics, in conjunction with the 
NCI CCR leadership committee analyzed the data.  The objective of the assessment was to make 
recommendations as to whether drug levels near that projected by the simulation can be achieved 
(feasibility, safety) and what, if any adjustments should be made with regard to the dose escalation 
and/ or study plan. The first assessment completed just prior to the implementation of Amendment 
F. leading to the new dose escalation plan and the addition of a bolus dose submitted in 
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Arm B2 – Continuous Infusion, Combination therapy: After the Part B Single Agent Lead-in 
is completed, assessment of continuous infusion of LMB-100 in combination with chemotherapy 
will be tested in the same population of pancreatic cancer patients enrolling in Part A. A single 
dose level of LMB-100 will be assessed in combination with chemotherapy in Phase I Part B.  This 
will require a maximum of 6 additional evaluable patients. If safety and tolerability of this 
combination is established in these 6 patients, then an additional 4 patients will be enrolled (total 
of 10 patients) to complete a small pilot investigation of the response rate of the combination of 
continuous infusion LMB-100 and Nab-paclitaxel. This is being kept deliberately small to permit 
more rapid assessment of any evidence of efficacy. These 10 patients’ clinical responses will be 
reported along with an appropriate confidence interval, and will be used to characterize the 
potential clinical efficacy of the combination. Therefore, 10 total participants with pancreatic 
cancer will be required to complete Phase I and pilot investigation of response rate. 
At the conclusion of the trial, the response information from the phase II portion of Part A and the 
pilot in Part B will be used to identify parameters which may merit further exploration in a more 
definitive subsequent trial. 
8.2 
DETERMINATION OF SAMPLE SIZE 
Part A: the phase I portion of the trial may require up to 12 participants, and the phase II portion, 
if explored, may require up to 20 evaluable participants. However, with 6 participants from phase 
I potentially being included in phase II, up to 12+20-6=26 individual participants may be required.  
Part B: The lead-in with single agent continuous LMB-100 may require up to 30 patients. 
Evaluation of the combination with nab-paclitaxel will require 10 patients if the combination is 
deemed safe and feasible.  Therefore, up to 40 patients may be required. 
Candidates for the phase 1 lead in portion of the study will be screened on the current protocol.  
With an anticipated screen failure rate of 50%, up to 30/0.5 = 60 subjects may need to enroll to 
this portion of the study.  With an additional 26 subjects required in part A (phase I and II) and 10 
subjects in the combination therapy portion of Part B, the overall accrual ceiling will be set at 100 
(26+60+10 +4 = 100 in order to allow for a small number of inevaluable participants).  If 1-2 
eligible pancreatic cancer patients enroll per month and 2-3 patients with other MSLN-expressing 
tumor types enroll on this trial, accrual would be expected to be completed in approximately 3 to 
5 years if the second stage of Phase II Part A is reached.  
9 
HUMAN SUBJECTS PROTECTIONS  
9.1 
RATIONALE FOR SUBJECT SELECTION 
LMB-100 is a mesothelin-targeted cFP and has shown preclinical dose-dependent activity in 
monotherapy and/or combination in xenografts representing MSLN-positive indications (NSCLC, 
mesothelioma, triple negative breast cancer, gastric cancer, pancreas, ovarian, potentially other 
tumor indications). The rationale to include MSLN- positive tumors of epithelial cell origin is 
based on preclinical models demonstrating promising anti-tumor efficacy. In addition, molecular 
pathology data demonstrated a high prevalence of mesothelin protein in these tumors. The 
rationale to evaluate LMB-100 in advanced/metastatic PDA and in mesothelin expressing solid 
tumors is to preliminarily assess the safety of LMB-100 alone or in combination with the standard 


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of care (SoC) chemotherapy nab-paclitaxel and We will also assess the preliminary anti-tumor 
activity of LMB-100 in PDA. 
9.2 
PARTICIPATION OF CHILDREN 
As this is a first in human study, there are no dosing or adverse event data are currently available 
on the use of LMB-100 in combination with nab-paclitaxel in participants <18 years of age; 
therefore, children are excluded from this study. 
9.3 
PARTICIPATION OF SUBJECTS UNABLE TO GIVE CONSENT 
Adults unable to give consent are excluded from enrolling in the protocol.  However re-consent 
may be necessary and there is a possibility, though unlikely, that subjects could become 
decisionally impaired. For this reason and because there is a prospect of direct benefit from 
research participation (section 9.5), all subjects will be offered the opportunity to fill in their wishes 
for research and care, and assign a substitute decision maker on the “NIH Advance Directive for 
Health Care and Medical Research Participation” form so that another person can make decisions 
about their medical care in the event that they become incapacitated or cognitively impaired during 
the course of the study. Note: The PI or AI will contact the NIH Ability to Consent Assessment 
Team (ACAT) for evaluation as needed for the following: an independent assessment of whether 
an individual has the capacity to provide consent; assistance in identifying and assessing an 
appropriate surrogate when indicated; and/or an assessment of the capacity to appoint a surrogate.  
For those subjects that become incapacitated and do not have pre-determined substitute decision 
maker, the procedures described in MAS Policy 87-4 and NIH HRPP SOP 14E for appointing a 
surrogate decision maker for adult subjects who are (a) decisionally impaired, and (b) who do not 
have a legal guardian or durable power of attorney, will be followed. 
9.4 
EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS 
9.4.1 Risks from Study Drugs 
Participant safety will be managed by careful proactive participant selection prior to study to 
exclude participants at risk from study treatment due to their pre-existing conditions. During the 
study, safety of participants will be proactively managed by protocol-mandated physical 
examinations, vital signs assessments, chest X-rays, ECGs, clinical laboratory assessments, and 
collection of adverse events and their assessment.  
The risks of the study include those associated with study agents as discussed in section 10. 
Additional risks may also be encountered from the use of the agents in combination as discussed 
below. 
9.4.1.1 Potential Toxicities of Combining LMB-100 with Nab-paclitaxel 
The most common clinically significant adverse reactions associated with the use of nab-paclitaxel 
have been neutropenia, peripheral neuropathy, arthralgia/myalgia, and gastrointestinal disorders. 
In the nab-paclitaxel treated population, the most frequently (t40% of participants) reported 
treatment emergent adverse events (TEAEs) were fatigue, nausea, peripheral neuropathy, alopecia, 
peripheral edema, diarrhea, anemia, neutropenia, and pyrexia. The most frequently reported Grade 
3 or higher TEAEs in the nab-paclitaxel arm were neutropenia, fatigue, peripheral neuropathy, 
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9.4.2 Risks of study procedures 
Study procedures such as research blood collection and ECGs are of minimal risk to the subject.  
Higher risk procedures performed include: 
9.4.2.1 CT Guided Research Biopsy 
The risks of the optional research biopsy collected in cycle 2 include pain, bleeding and infection 
at the biopsy site.  In addition, as the biopsy may be collected under CT guidance, subjects in this 
study may be exposed to approximately 0.77 rem.  This amount is below the guideline of 5 rem 
per year allowed for adult research subjects by the NIH Radiation Safety Committee.  
9.4.2.2 Central Line Insertion 
All subjects in Arms B1 and B2 are required to receive study therapy through a central line or an 
existing mediport. In addition, per PI discretion, some subjects in Arms A1 and A2 may also 
require central line insertion. The risks of this procedure include catheter contamination, 
pneumothorax, arrhythmia and air embolus.  All care will be taken to minimize complications of 
central insertion during the procedure. 
9.5 
RISKS/BENEFITS ANALYSIS 
Patients with advanced and/or metastatic cancer are in continuous need of improved therapy 
options. This is especially true for patients where no standard therapy exists such as the population 
that will be eligible for this trial. Preclinical data has demonstrated promising anti-tumor efficacy 
of LMB-100 in xenograft models in monotherapy and even more so when LMB-100 has been 
combined with chemotherapy. Therefore, LMB-100 may improve clinical outcome of patients 
with pancreatic ductal adenocarcinoma in combination with nab-paclitaxel, an approved agent in 
advanced/metastatic PDA as well as the outcome of patients with mesothelin positive solid tumors 
receiving LMB-100 monotherapy. A number of clinically appropriate strategies to minimize risk 
to participants have been built into the protocol through the means of inclusion/exclusion criteria, 
monitoring strategies, and management guidelines.  
Overall, the potential benefits of LMB-100 for cancer participants, those able to consent and those 
who lose the capacity to do so during the course of the trial, outweigh the risks associated with the 
proposed entry-into-human trial with LMB-100. 
9.6 
CONSENT AND ASSENT PROCESS AND DOCUMENTATION 
All participants will be thoroughly screened by the physician and the research nurse prior to 
completing the consent. During the initial consultation, the participant and family or friends, if 
present, will be presented with a forthright and detailed overview of the treatment option available 
to them at the NIH. The experimental nature of the treatment, its objectives, its theoretical 
advantages and disadvantages will be presented. The Informed Consent document is given to the 
participant and they are asked to review it, make notes and ask questions prior to agreeing to 
participate in this protocol. The participant is reassured that participation on this trial is entirely 
voluntary and that he/she can withdraw or decide against treatment at any time without adverse 
consequences. The physician assures the participant that if alternative therapy or no therapy at all 
is preferred, we will do all that we can to facilitate consultation with the appropriate referral 
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patient refuses the optional biopsy at that time, the refusal will be documented in the medical 
record and in the research record. 
The Informed Consent document may be obtained from the participant by the principal 
investigator, associate investigators, or the medical staff fellow under the supervision of the 
principal investigator. 
9.6.1 Consent procedure for non-English speaking patients 
If there is an unexpected enrollment of a research participant for whom there is no translated extant 
IRB approved consent document, the principal investigator and/or those authorized to obtain 
informed consent will use the Short Form Oral Consent Process as described in MAS Policy M77-
2, OHSRP SOP 12, 45 CFR 46.117 (b) (2), and 21 CFR 50.27 (b) (2).  The summary that will be 
used is the English version of the extant IRB approved consent document.  Signed copies of both 
the English version of the consent and the translated short form will be given to the subject or their 
legally authorized representative and the signed original will be filed in the medical record. 
Unless the PI is fluent in the prospective subject’s language, an interpreter will be present to 
facilitate the conversation. Preferably someone who is independent of the subject (i.e., not a family 
member) will assist in presenting information and obtaining consent. Whenever possible, 
interpreters will be provided copies of the relevant consent documents well before the consent 
conversation with the subject (24 to 48 hours if possible).  
We request prospective IRB approval of the use of the short form process and will notify the IRB 
at the time of continuing review of the frequency of the use of the Short Form. 
9.6.2 Telephone consent procedure 
Consent for screening and re-consent on this study may be obtained via telephone according to the 
following procedure: the informed consent document will be sent to the subject.  An explanation 
of the study will be provided over the telephone after the subject has had the opportunity to read 
the consent form.  The subject will sign and date the informed consent. A witness to the subject’s 
signature will sign and date the consent.  The original informed consent document will be sent 
back to the consenting investigator who will sign and date the consent form with the date the 
consent was obtained via telephone.  A fully executed copy will be returned via mail for the 
subject’s records.  The informed consent process will be documented on a progress note by the 
consenting investigator. 
10 PHARMACEUTICAL INFORMATION   
Nab-paclitaxel is approved for use as a first line agent in metastatic pancreatic cancer.  It is not 
approved for use as a second line agent, the use in the current protocol.  The investigation is not 
intended to support a new indication for use or any other significant changes to labeling or 
advertising in any of the commercial agents used on the study.  The investigation does not involve 
a route of administration or dosage level in use in a patient population or other factor that 
significantly increases the risks (or decreases the acceptability of the risks) associated with the use 
of the drug products. 


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10.1 LMB-100 (IND # 123332) 
10.1.1 Source  
LMB-100 was transferred to the NIH CC Pharmacy by Roche, the drug manufacturer.  For this 
trial, the drug will be supplied by the NIH CC Pharmacy.  
10.1.2 Toxicity  
Information in this section is based on preclinical studies with LMB-100, and clinical studies of the 
cytolytic fusion protein SS1-P. Participants should receive a full dose of LMB-100 unless a DLT 
and/or a treatment limiting toxicity is observed. In case of DLT and/or treatment limiting toxicities, 
treatment with LMB-100 will be stopped until resolution of toxicity to NCI CTCAE Grade d2 
hematological toxicities or Grade d1 non-hematological toxicities. A delay of LMB-100 
administration for up to two weeks of the planned schedule will be acceptable to allow for 
resolution of toxicity to NCI CTCAE Grade d2 hematological toxicities or Grade d1 non-
hematological toxicities. If toxicity does not resolve to NCI CTCAE Grade d2 hematological 
toxicities or Grade d1 non-hematological toxicities and the participant is unable to resume 
treatment with LMB-100 after this time, no additional doses will be administered and the 
participant will be withdrawn from study treatment. 
10.1.2.1 Infusion-Related Reactions and Hypersensitivity Including Anaphylaxis 
LMB-100 administration may cause infusion-associated symptoms such as fever, chills, 
hypotension, shortness of breath, skin rash, headache, nausea, and/or vomiting. Such reactions 
typically occur during or shortly after an infusion. Participants may also develop IgE-mediated 
hypersensitivity reactions to LMB-100. IRRs may be indistinguishable from an anaphylactic 
reaction. Participants should receive full supportive care to treat IRRs or anaphylaxis according to 
institutional practice. If infusion-associated signs or symptoms occur, participants should be 
monitored until complete resolution. 
In vitro data and previous clinical experience with LMB-100 suggest that the risk for the release of 
pro-inflammatory cytokines upon first administration of LMB-100 to humans is low (human whole 
blood assay, see section 1.2.4.1.4). Past experience with monoclonal antibodies that demonstrated 
a risk in the whole blood assay has shown that this risk could be effectively managed in the clinic 
with appropriate risk-minimization measures. The release of pro-inflammatory cytokines is 
believed to be partially responsible for the occurrence of IRRs. 
10.1.2.2 Risk of Immunogenicity and Potential Safety Impact 
LMB-100 may cause the formation of ADAs. These may trigger hypersensitivity reactions or 
immune complex-mediated responses. The development of ADAs to LMB-100, an improved 
cytolytic fusion protein with a humanized targeting moiety directed against mesothelin and a de-
humanized, truncated Pseudomonas exotoxin A is expected to be less likely than SS1P. Clinical 
trials with SS1P have led to the development of neutralizing ADAs in 75% and 88% of participants 
after 1 cycle of therapy, in the IV bolus and continuous infusion trials respectively.[31]  
Participants will be monitored at regular intervals for the development of ADAs and cytokines. In 
particular, any clinical signs and symptoms suggestive of a hypersensitivity reaction and/or an 
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10.1.2.3 Risk of Inflammatory Reactions to Serosal Membranes  
LMB-100 administration may cause inflammatory reactions to serosal membranes including 
pleuritis, characterized by pleuritic chest pain, dyspnea, and hypoxia and pericarditis, characterized 
by precordial chest pain, congestive heart failure, hypotension, and uremia. Clinical trials with 
SS1P monotherapy have led to reversible pleuritis and pericarditis. Participants who develop 
symptoms of serosal inflammation should be closely monitored and receive standard treatments 
which may include corticosteroids. 
10.1.2.4 Risk of Vascular Leak Syndrome 
LMB-100 administration may cause VLS characterized by hypotension, hypoalbuminemia, edema, 
weight gain, and hemoconcentration. Clinical trials with SS1P monotherapy have led to the 
development of reversible VLS. Participants will be monitored with frequent assessments of chest 
x-rays, weight, edema, blood pressure, and serum albumin levels prior to and during treatment. 
Participants who develop symptoms of VLS should be closely monitored and receive standard 
symptomatic treatments. 
10.1.2.5 Risk of Renal Toxicity 
LMB-100 administration may cause renal toxicity characterized by increased creatinine, BUN, and 
proteinuria. In preclinical cynomolgus monkey studies, LMB-100 has shown increases in 
creatinine and histological changes including regenerative and degenerative changes to the tubular 
epithelium. Hemolytic uremic syndrome has been reported for other cytolytic fusion antibodies in 
development. 
Participants should be monitored with renal laboratory assessments including creatinine, BUN, and 
urinalysis. 
10.1.2.6 Injection Site Reactions 
LMB-100 administration may cause adverse reactions at the infusion site characterized by pain, 
swelling, induration, and nodules. In preclinical NHP studies for both SS1P and LMB-100 
reddening and swelling of the infusion site were noted. Participants who develop symptoms of 
infusion site reactions can be administered pain relieving medication (analgesic) as required, and 
rotation of infusion sites is recommended. 
10.1.2.7 Pregnancy 
No studies assessing the reproductive and developmental toxicity of LMB-100 have been 
conducted to date. It is not known whether LMB-100 can cross the placenta or cause harm to the 
fetus when administered to pregnant women or whether it affects reproductive capacity. LMB-100 
should not be administered to pregnant women. 
10.1.3 Formulation and preparation  
LMB-100 drug product (20 mg/20 mL) is provided for syringe infusion as a sterile, colorless to 
brownish, preservative-free liquid in single-use, 20 mL vials. The nominal fill volume is 20 mL 
and the approximate concentration of LMB-100 recombinant fusion protein in the vials is 1 mg/mL. 


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10.1.4 Stability and Storage  
Chemical and physical in-use stability for undiluted LMB-
100 drug product in syringes has been demonstrated for 24 
hours at 2-8 °C and 24 hours at ambient temperature. 
Storage conditions should generally be at 2-8qC, but 
syringes may be held at room temperature for up to a 
maximum of 4 hours. 
Roche has extensively studied the stability of LMB-100.  
Vials of LMB-100 can be stored at 4°C for at least 24 
months without loss of activity or degradation of the drug 
product. At 25°C, no loss of activity is observed over a 4-
week period, and 94% of potency is retained even after 3 
months of exposure to this temperature (Figure 9). 
However, when vials of LMB-100 are exposed to 
temperatures of 37°C, the drug begins to lose activity 
within 12 hours.  
10.1.5 Administration procedures 
Please refer to section 3.2.1 
10.1.6 Incompatibilities   
Pharmacodynamic drug interaction studies have not been conducted. LMB-100 is contraindicated 
in subjects with a history of severe allergic anaphylactic reactions to humanized, chimeric or 
mouse peptides/antibodies or to any components of the product. 
10.1.6.1 Mechanism of action 
LMB-100 is a novel recombinant anti-mesothelin targeted cytolytic fusion protein (cFP) 
developed for the treatment of participants with solid tumors that express the mesothelin protein.  
Mesothelin is a suitable candidate for targeted therapy due to its very limited expression in 
normal/non-malignant tissue and its high expression in several tumor entities including 
mesothelioma, ovarian cancer, pancreatic cancer, gastric cancer, breast cancer, and lung cancer. 
To target mesothelin, a humanized Fab fragment of the anti-mesothelin antibody SS1 is linked to 
a truncated and de-immunized recombinant 24 kD fragment of Pseudomonas exotoxin (PE24).  
After binding to mesothelin, the complex is internalized by endocytosis and kills cells by inhibition 
of eukaryotic elongation factor 2 (eEF2), leading to arrest of protein synthesis and secondarily 
triggering cell death by apoptosis or necrosis. 
Figure 9 


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10.1.6.2 Molecular Weight: approximately 73 kDa 
10.1.6.3 Chemical Structure 
 
H1L1 polypeptide structure consisting of one variable heavy chain containing the Pseudomonas 
Exotoxin A moiety and one variable light change held together by a disulfide bond. 
10.2 NAB-PACLITAXEL 
Please refer to package insert for additional information. 
10.2.1 Source  
Nab-paclitaxel will be purchased from commercial sources by the NIH CC Pharmacy. 
10.2.2 Toxicity  
The most common clinically significant adverse reactions reported with nab-paclitaxel in patients 
with pancreatic cancer include: neutropenia, anemia, thrombocytopenia, pancytopenia peripheral 
neuropathy, cardiac failure, tachycardia, dyspnea, pneumonitis, nausea, vomiting, diarrhea 
abdominal pain, intestinal obstruction, colitisarthralgia/myalgia, renal failure, increased alanine 
aminotransferase, increased aspartate aminotransferase, increased bilirubin, and 
increased 
creatinine. 
Hypersensitivity reactions including fatal anaphylactic reactions have rarely been reported with 
nab-paclitaxel. If a hypersensitivity reaction occurs, nab-paclitaxel should 
be discontinued 
immediately, symptomatic treatment should be initiated, and the participant should not be 
rechallenged with paclitaxel. 


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Bone marrow suppression (primarily neutropenia) occurs frequently with nab-paclitaxel. Frequent 
monitoring of blood cell counts should be performed. Participants should not be retreated with 
subsequent cycles of nab-paclitaxel until neutrophils recover to !1500 cells/mm2 and platelets to 
!100,000 cells. 
Sensory neuropathy occurs frequently with nab-paclitaxel, though generally not severe. The 
occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose reduction.  
Sepsis was reported in 5% of participants with or without neutropenia who received nab- 
paclitaxel.[52] Complications due to underlying pancreatic cancer, especially biliary obstruction or 
presence of biliary stent, were identified as significant contributing factors. 
Pneumonitis occurred in 4% of participants using nab-paclitaxel. Closely monitor all participants 
for signs and symptoms of pneumonitis. After ruling out infectious etiology and upon making a 
diagnosis of pneumonitis, permanently discontinue treatment with nab-paclitaxel and promptly 
initiate appropriate treatment with supportive measures. 
Hepatic impairment may increase the toxicity of nab-paclitaxel, particularly myelosuppression. 
Administration of nab-paclitaxel in participants with hepatic impairment should be performed with 
caution. 
Congestive heart failure and left ventricular dysfunction have rarely been observed in participants 
receiving nab-paclitaxel. Most of these participants were previously exposed to cardiotoxic 
medicinal products such as anthracyclines or had underlying cardiac history. Participants receiving 
nab-paclitaxel should be vigilantly monitored for the occurrence of cardiac events. 
Nausea, vomiting, and diarrhea following administration of nab-paclitaxel may be treated with 
commonly used anti-emetics and constipating agents. 
In the very elderly ( ≥75 years) who received nab-paclitaxel, there was a higher incidence of serious 
adverse reactions and adverse reactions that led to discontinuation including hematologic toxicities, 
peripheral neuropathy, decreased appetite, and dehydration. Participants 75 years or older should 
be carefully assessed for their ability to tolerate nab-paclitaxel with special consideration to 
performance status, co-morbidities, and increased risk of infections. 
10.2.3 Formulation and preparation  
Formulation 
ABRAXANE is supplied as a lyophilized powder containing 100 mg of paclitaxel formulated as 
albumin-bound particles in single-use vial for reconstitution. 
Preparation 
1. Aseptically, reconstitute each vial by injecting 20 mL of 0.9% Sodium Chloride Injection, 
USP. 
2. Slowly inject the 20 mL of 0.9% Sodium Chloride Injection, USP, over a minimum of 1 
minute, using the sterile syringe to direct the solution flow onto the INSIDE WALL OF 
THE VIAL. 


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3. DO NOT INJECT the 0.9% Sodium Chloride Injection, USP, directly onto the lyophilized 
cake as this will result in foaming. 
4. Once the injection is complete, allow the vial to sit for a minimum of 5 minutes to ensure 
proper wetting of the lyophilized cake/powder. 
5. Gently swirl and/or invert the vial slowly for at least 2 minutes until 
complete dissolution of any cake/powder occurs. Avoid generation of foam. 
6. If foaming or clumping occurs, stand solution for at least 15 minutes until foam subsides. 
Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel. 
Calculate the exact total dosing volume of 5 mg/mL suspension required for the participant: 
Dosing volume (mL) = Total dose (mg)/5 (mg/mL) 
The reconstituted suspension should be milky and homogenous without visible particulates. If 
particulates or settling are visible, the vial should be gently inverted again to ensure complete 
resuspension prior to use. Discard the reconstituted suspension if precipitates are observed. 
Discard any unused portion. 
Inject the appropriate amount of reconstituted ABRAXANE® into an empty, sterile IV bag 
(plasticized polyvinyl chloride (PVC) containers, PVC or non-PVC type IV bag). The use of 
specialized DEHP-free solution containers or administration sets is not necessary to prepare or 
administer ABRAXANE infusions. The use of an in-line filter is not recommended. 
Parenteral drug products should be inspected visually for particulate matter and discoloration prior 
to administration whenever solution and container permit. 
10.2.4 Stability and Storage  
Unopened vials of ABRAXANE are stable until the date indicated on the package when stored 
between 20°C to 25°C (68°F to 77°F), in the original package. Neither freezing nor refrigeration 
adversely affects the stability of the product.  Product should be retained in the original packaging 
to protect from bright light. 
Stability of Reconstituted Suspension in the Vial 
Reconstituted ABRAXANE should be used immediately, but may be refrigerated at 2°C to 8°C 
(36°F to 46°F) for a maximum of 24 hours if necessary. If not used immediately, each vial of 
reconstituted suspension should be replaced in the original carton to protect it from bright light. 
Discard any unused portion. 
Stability of Reconstituted Suspension in the Infusion Bag 
The suspension for infusion when prepared as recommended in an infusion bag should be used 
immediately, but may be refrigerated at 2°C to 8°C (36°F to 46°F) and protected from bright light 
for a maximum of 24 hours... 


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10.2.5 Administration procedures 
Please see section 3.2.2. 
10.2.6 Incompatibilities   
Please refer to the package insert. 
 


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Summary 
of 
opinion 
– 
ABRAXANE 
(available 
online 
at: 
http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2013/11/W 
C500155476.pdf ). 
 
 


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12 APPENDICES 
12.1 APPENDIX A – PERFORMANCE STATUS CRITERIA 
ECOG Performance Status Scale 
 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity.  Fully active, able 
to 
carry 
on 
all 
pre-disease 
performance without restriction. 
100 
Normal, 
no 
complaints, 
no 
evidence of disease. 
90 
Able to carry on normal activity; 
minor signs or symptoms of 
disease. 
1 
Symptoms, 
but 
ambulatory.  
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). 
80 
Normal activity with effort; some 
signs or symptoms of disease. 
70 
Cares for self, unable to carry on 
normal activity or to do active 
work. 
2 
In bed <50% of the time.  
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities.  Up and about 
more than 50% of waking hours. 
60 
Requires occasional assistance, 
but is able to care for most of 
his/her needs. 
50 
Requires considerable assistance 
and frequent medical care. 
3 
In bed >50% of the time.  Capable 
of only limited self-care, confined 
to bed or chair more than 50% of 
waking hours. 
40 
Disabled, requires special care 
and assistance. 
30 
Severely disabled, hospitalization 
indicated.  Death not imminent. 
4 
100% bedridden.  Completely 
disabled.  Cannot carry on any 
self-care.  Totally confined to bed 
or chair. 
20 
Very 
sick, 
hospitalization 
indicated. Death not imminent. 
10 
Moribund, 
fatal 
processes 
progressing rapidly. 
5 
Dead. 
0 
Dead. 
 
 
 


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12.2 APPENDIX B – COCKCROFT-GAULT FORMULA FOR CALCULATION OF CREATININE 
CLEARANCE 
 
 
 
 


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12.3 APPENDIX C: SAMPLE CHEMOTHERAPY NOTES  
12.3.1 For Part A 
 
(1) 
Nab-paclitaxel, 125 mg/m2, IV over 30 minutes ± 10 minutes on Days 1 and 8 
 
(2) 
LMB-100, <dose as per escalation scheme> mcg/kg, IV on Days 1, 3 and 5 
On Day 1, administer 30 minutes ± 20 minutes following completion of Nab-paclitaxel infusion 
 
Pre-medications: 
o Diphenhydramine 25-50 mg PO or IV 
o Ranitidine 150 mg PO 
o Acetaminophen 650 mg PO 
 
Additional medications: 
-Dexamethasone 8 mg IV, PRN severe infusion related reaction (should be available on unit) 
-Ondansetron 8 mg PO q8h, PRN nausea 
 
Please encourage oral hydration of 1.5 to 2L daily while receiving LMB-100. 
 
 


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12.3.2 For Arm B1 
 
(1)  
Loading dose of LMB-100 
LMB-100, 40 mcg/kg, IV on Day 1 and if applicable, Day 4 
 
Continuous infusion LMB-100 to immediately following loading dose on Day 1 and if applicable, 
Day 4 
LMB-100, <dose as per escalation scheme> mcg/kg/day IV, for # hrs  
Syringes of drug must be changed q12hrs. In-line filtration required.   
Dose per 12 hours = <dose as per escalation scheme> / 2 = # mcg/kg 
Infusion rate = <Dose per 12 hours> / 12 = # ml/hr 
Run with Normal Saline at 20cc/hour IV for in-line dilution. 
 
Pre-medications on Day 1: 
o Diphenhydramine 25-50 mg PO or IV 
o Ranitidine 150 mg PO 
o Acetaminophen 650 mg PO 
 
Additional medications: 
-Dexamethasone 8 mg IV, PRN severe infusion related reaction (should be available on unit) 
-Ondansetron 8 mg PO q8h, PRN nausea 
 
Please encourage oral hydration daily of 1.5 to 2L daily while receiving LMB-100. 
 
 


Abbreviated Title: LMB-100 + Abrx in PDA 
Version Date: 12/11/2018 
 
118 
 
12.3.3  For Arm B2  
 
(1) 
Nab-paclitaxel, 125 mg/m2, IV over 30 minutes ± 10 minutes on Days 1  
 
(2) 
Loading dose of LMB-100 
LMB-100, 40 mcg/kg, IV on Day 1  
 
Continuous infusion LMB-100 to immediately following loading dose on Day 1  
LMB-100, 100 mcg/kg/day IV, for 24 hrs  
Syringes of drug must be changed q12hrs. In-line filtration required.   
Dose per 12 hours = 50 mcg/kg * <patient weight> = # mg 
Infusion rate = <Dose per 12 hours (mg)> / 1 mg/mL / 12 hrs = # ml/hr 
Run with Normal Saline at 20cc/hour IV for in-line dilution. 
On Day 1, administer 30 minutes ± 20 minutes following completion of Nab-paclitaxel infusion 
 
Pre-medications: 
o Diphenhydramine 25-50 mg PO or IV 
o Ranitidine 150 mg PO 
o Acetaminophen 650 mg PO 
 
Additional medications: 
-Dexamethasone 8 mg IV, PRN severe infusion related reaction (should be available on unit) 
-Ondansetron 8 mg PO q8h, PRN nausea 
 
Please encourage oral hydration of 1.5 to 2L daily while receiving LMB-100. 
 

ICF_001.pdf: 
MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
16-C-0128 
PRINCIPAL INVESTIGATOR: 
Christine Alewine, M.D., Ph.D. 
STUDY TITLE:  
A Phase I/II Study of Mesothelin-Targeted Immunotoxin LMB-100 Alone or in 
Combination with Nab-Paclitaxel in Participants with Previously Treated Metastatic and/ 
or Locally Advanced Pancreatic Ductal Adenocarcinoma and Mesothelin Expressing 
Solid Tumors 
 
Continuing Review Approved by the IRB on 08/31/20 
Amendment Approved by the IRB on 12/13/18 (L) 
 
Date posted to web:  09/04/20 
Screening  
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent (3) 
 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary.  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
You may receive no benefit from taking part.  The research may give us knowledge that 
may help people in the future. 
Second, 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).  If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
Now we will describe this research study.  Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional.   
Why is this study being done?  
LMB-100 is an investigational agent, meaning that it has not been approved by the US Food and 
Drug Administration. It is a type of manufactured protein which is similar to protein normally 
produced by your body.  LMB-100 is attracted to the mesothelin protein, which is present on the 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 2 of 8 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
surface of many different tumors. The mesothelin protein is found in only a very small number 
of normal tissues.  After binding to the mesothelin on tumors, LMB-100 can then attack and kill 
cancer cells.  
In this study, we will test different schedules of LMB-100 dosing and different doses of LMB-
100 in combination with nab-paclitaxel, an FDA approved drug.  In one part of the study, the 
part in which you may be participating, we are testing a safe dose of LMB-100 alone.  This is the 
Arm B1, continuous infusion single agent lead-in portion of the study. 
In order to be eligible to participate in this portion of the study, unless you have pancreatic 
cancer or a type of mesothelioma called epithelioid, we need to test whether your tumor cells 
have mesothelin.  Please be aware that the test that will be used in this study determine the 
mesothelin status of your tumor is experimental (Investigational Device) and is limited by United 
States law to experimental use. Experimental means that the test is not approved by the U. S. 
Food and Drug Administration (FDA) and is still being tested in research studies. 
Why are you being asked to take part in this study? 
You are being asked to take part in this study because you have a solid tumor that has worsened 
after anti-cancer therapy.  
How many people will take part in this study?  
Up to 100 participants will be enrolled in the study overall. 
Description of Research Study 
The following tests will be performed to determine whether you are eligible to participate.   
x Confirmation of diagnosis (You must provide a sample tumor tissue for formal evaluation 
by the NCI Laboratory of Pathology.  The tissue may be from a previous surgery or 
biopsy.  If none is available, we will ask you to have a biopsy to provide a fresh sample).   
x Mesothelin testing.  Previously collected tissue from your tumor or any leftover tissue 
that may be collected for the confirmation of diagnosis will be used to determine whether 
your tumor cells have mesothelin, unless you have pancreatic cancer or a type of 
mesothelioma referred to as epithelioid. 
x Medical history and physical examination 
x Routine blood and urine tests including pregnancy test in women who can have children.  
Pregnant women will not be allowed on study. 
x Scans and x-rays 
x Electrocardiogram (ECG) 
x Echocardiogram 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 3 of 8 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
x Blood for tumor markers 
Risks or Discomforts of Participation 
The following study procedures 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.  
ECGs 
The glue used to keep the electrodes in place during the ECG may irritate your skin and caused 
redness.  
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, infection or of an allergic reaction to 
the anesthetic agent used to anesthetize the skin at the biopsy site.  Once the sample has been 
obtained, a stitch may be used to close the wound and assist in healing.   
Potential Benefits of Participation 
Are there benefits to taking part in this study?  
The aim of this study is to find a safe dose as well as to see if this experimental treatment will 
cause your tumors to shrink.  We do not know if you will receive personal, medical benefit from 
taking part in this study.  If you are eligible and receive treatment, these potential benefits could 
include shrinking of your tumor or lessening of 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, although the knowledge gained from 
this study may help others in the future who have cancer.   
What other choices do I have if I do not take part in this study?  
Instead of being in this study, you have these options: 
x You may choose not to be tested for eligibility. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 4 of 8 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Research Subject’s Rights 
What are the costs of taking part in this study?  
If you choose to take part in the study, the following will apply, in keeping with the NIH policy: 
x 
You will receive study treatment at no charge to you. This may include 
surgery, medicines, laboratory testing, x-rays or scans done at the 
Clinical Center, National Institutes of Health (NIH), or arranged for you 
by the research team to be done outside the Clinical Center, NIH if the 
study related treatment is not available at the NIH.  
x 
There are limited funds available to cover the cost of some tests and 
procedures performed outside the Clinical Center, NIH.  You may have 
to pay for these costs if they are not covered by your insurance company. 
x 
Medicines that are not part of the study treatment will not be provided or 
paid for by the Clinical Center, NIH. 
x 
Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
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: 
x The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), which are involved in keeping research safe for people. 
x NIH Intramural Institutional Review Board 
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.  
Certificate of Confidentiality  
To help us protect your privacy, we have obtained a Certificate of Confidentiality. The 
researchers can use this Certificate to legally refuse to disclose information that may identify you 
in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for 
example, if there is a court subpoena. The researchers will use the Certificate to resist any 
demands for information that would identify you, except as explained below. 
You should also know that there are several circumstances in which the Certificate does not 
provide coverage. These include when information:  
x will be used for auditing or program evaluation internally by the NIH; or  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 5 of 8 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
x must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA).  
x is necessary for your medical treatment and you have consented to this disclosure;  
x is for other research.  
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible 
as evidence or used for any purpose in any action, suit, or proceeding without your consent.  
You should understand that a Certificate of Confidentiality does not prevent you or a member of 
your family from voluntarily releasing information about yourself or your involvement in this 
research. If an insurer, employer, or other person obtains your written consent to receive research 
information, then the researchers will not use the Certificate to withhold that information. 
The Certificate of Confidentiality will not protect against the required reporting by hospital staff 
of information on suspected child abuse, reportable communicable diseases, and/or possible 
threat of harm to self or others. 
Stopping Participation  
Your doctor may decide to remove you from the study for the following reasons: 
x if you are found to be ineligible 
You can stop taking part in the study at any time. 
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. However, according to FDA guidelines, 
information collected on you up to that point may still be provided to collaborators or designated 
representatives. If you withdraw your consent and leave the trial, any samples of yours that have 
been obtained for the study and stored at the NCI can be destroyed upon request. However, any 
samples and data generated from the samples that have already been distributed to other 
researchers or placed in the research databases cannot be recalled and destroyed. 
Conflict of Interest 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a Protocol Review Guide.  You may ask your research 
team for a copy of the Protocol Review Guide or for more information.  Members of the research 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study.  This is allowed under federal rules and is not a 
conflict of interest.  


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 6 of 8 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
The National Institutes of Health and the research team for this study have developed a drug 
being used in this study.  This means it is possible that the results of this study could lead to 
payments to NIH scientists and to the NIH. By law, government scientists are required to receive 
such payments for their inventions. You will not receive any money from the development of 
LMB-100 in combination with nab-paclitaxel.  
Use of Specimens and Data for Future Research 
To advance science, it is helpful for researchers to share information they get from studying 
human samples.  They do this by putting it into one or more scientific databases, where it is 
stored along with information from other studies. A researcher who wants to study the 
information must apply to the database and be approved.  Researchers use specimens and data 
stored in scientific databases to advance science and learn about health and disease.   
We plan to keep some of your specimens and data that we collect and use them for future 
research and share them with other researchers. We will not contact you to ask about each of 
these future uses.  These specimens and data will be stripped of identifiers such as name, address 
or account number, so that it may be used for future research on any topic and shared broadly for 
research purposes. Your specimens and data will be used for research purposes only and will not 
benefit you.  It is also possible that the stored specimens and data may never be used.  Results of 
research done on your specimens and data will not be available to you or your doctor.  It might 
help people who have cancer and other diseases in the future.   
If do not want your stored specimens and data used for future research, please contact us in 
writing and let us know that you do not want us to use your specimens and/or data.  Then any 
specimens that have not already been used or shared will be destroyed and your data will not be 
used for future research. However, it may not be possible to withdraw or delete materials or data 
once they have been shared with other researchers. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 16-C-0128 
CONTINUATION: page 7 of 8 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
OTHER PERTINENT INFORMATION 
1. 
Confidentiality.  When results of an NIH research study are reported in medical journals 
or at scientific meetings, the people who take part are not named and identified.  In most cases, 
the NIH will not release any information about your research involvement without your written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance 
company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration (FDA), 
members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
2. 
Policy Regarding Research-Related Injuries.  The 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 National Institutes of Health, the Clinical Center, or the Federal Government.  
However, you have the right to pursue legal remedy if you believe that your injury justifies such 
action. 
3. 
Payments.  The amount of payment to research volunteers is guided by the National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies at 
the National Institutes of Health.  Reimbursement of travel and subsistence will be offered 
consistent with NIH guidelines. 
4. 
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, Christine Alewine, M.D., Ph.D., Building 37, Room 5116, Telephone:  
240-760-6146. You may also call the Clinical Center Patient Representative at 301-496-2626. If 
you have any questions about the use of your specimens or data for future research studies, you 
may also contact the Office of the Clinical Director, Telephone:  240-760-6070. 
5. 
Consent Document.  Please keep a copy of this document in case you want to read it 
again. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 16-C-0128 
CONTINUATION: page 8 of 8 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
 
 
 
Signature of Adult Patient/ 
Legal Representative 
Date 
 
 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to 
participate in the study. 
 
  
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM AUGUST 31, 2020 THROUGH AUGUST 30, 2021. 
 
 
 
 
 
 
 
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name 
 

ICF_003.pdf: 
MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
16-C-0128 
PRINCIPAL INVESTIGATOR: 
Christine Alewine, M.D., Ph.D. 
STUDY TITLE:  
A Phase I/II Study of Mesothelin-Targeted Immunotoxin LMB-100 Alone or in 
Combination with Nab-Paclitaxel in Participants with Previously Treated Metastatic and/ 
or Locally Advanced Pancreatic Ductal Adenocarcinoma and Mesothelin Expressing 
Solid Tumors 
 
Continuing Review Approved by the IRB on 08/31/20 
Amendment Approved by the IRB on 12/13/18 (L) 
 
Date posted to web: 09/04/20  
Arm A2 (Phase 2 Short Infusion) 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent (5) 
 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary.  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
You may receive no benefit from taking part.  The research may give us knowledge that 
may help people in the future. 
Second, 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).  If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
Now we will describe this research study.  Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional.   
Why is this study being done?  
LMB-100 is an investigational agent, meaning that it has not been approved by the US Food and 
Drug Administration. It is a type of manufactured protein which is similar to protein normally 
produced by your body.  LMB-100 is attracted to the mesothelin protein, which is present on the 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 2 of 14 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
surface of many different tumors, including many, but not all, pancreatic cancers. The 
mesothelin protein is found in only a very small number of normal tissues.  After binding to the 
mesothelin on tumors, LMB-100 can then attack and kill cancer cells.  
Nab-paclitaxel is an FDA approved agent in the treatment of pancreatic cancer. It has not, 
however been tried in combination with LMB-100. 
This study, which is divided into multiple parts will determine a safe dose of LMB-100 on 
different administration schedules alone or in combination with a fixed dose of nab-paclitaxel in 
the phase 1 portion. 
x In phase 1, Arm A1 – subjects with pancreatic cancer will receive nab-paclitaxel in 
combination with LMB-100 given every other day for 3 days in each 21-day cycle. 
x In phase 1, Arm B1, (single Agent lead-in) – subjects that have tumors that test positive 
for mesothelin will receive LMB-100 alone for 1 or 2 days continuously or two 24-hour 
infusions (days 1 and 4) depending on dose level in each 21-day cycle. 
x In phase 1, Arm B2, (combination therapy) – subjects with pancreatic cancer will receive 
nab-paclitaxel in combination with LMB-100 given for 24 hours continuously on day 1 
of each 14-day cycle.  
In the phase 2 portion of the study (Arm A2), we will determine whether the dose established in 
phase 1, Arm A1 reduces the size of tumors in patients with pancreatic cancer. 
You are participating in the phase 2, Arm A2 portion of the study. 
Why are you being asked to take part in this study? 
You are being asked to take part in this study because you have advanced pancreatic cancer that 
has worsened after anti-cancer therapy.  
How many people will take part in this study?  
Up to 100 participants will be enrolled in the study overall. 
Description of Research Study 
You will receive LMB-100 at the safe dose determined in the phase 1, Arm A1 portion of the 
study through an IV catheter (a tube inserted in a vein, usually in your arm though, as stated 
below in During the Study, it may be placed in a different location if your doctor feels it is 
necessary) on day 1, day 3 and day 5 of each 21-day cycle.  Nab-paclitaxel will also be given by 
IV on days 1 and 8 of each 21-day cycle. You will receive LMB-100 in combination with nab-
paclitaxel for up to 2 cycles or until your disease worsens or you have intolerable side effects, 
whichever happens first. We will continue to follow you after you have finished taking the study 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 3 of 14 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
drug to keep track of your disease status (progression), your survival status or whether you have 
taken any additional cancer therapy.  The specific procedures you will have are described below. 
What will happen if you take part in this research 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 
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 are performed under a separate consent, include: 
x Confirmation of diagnosis (You must provide a sample tumor tissue for formal evaluation 
by the NCI Laboratory of Pathology.  The tissue may be from a previous surgery or 
biopsy.  If none is available, we will ask you to have a biopsy to provide a fresh sample).   
x Medical history and physical examination 
x Routine blood and urine tests including pregnancy test in women who can have children.  
Pregnant women will not be allowed on study. 
x Scans  
x Electrocardiogram (ECG) 
x Echocardiogram 
x Tests for viruses (hepatitis and HIV) 
x Blood for tumor markers 
During the study 
Once it is determined that you are eligible and you have signed the consent for the study, you 
will receive IV infusions of LMB-100 and nab-paclitaxel as described above. Each LMB-100 
infusion will last for as long as 3 hours.  Each nab-paclitaxel infusion lasts about 30 minutes. If 
your doctor feels that it is necessary, you may receive the study drugs through a central line (an 
IV tube placed in a large vein for long term therapy) or through a mediport if you already have 
one installed. On day 1 of each cycle, when both medications are given, you will receive the 
LMB-100 about 30 minutes after you have completed the nab-paclitaxel infusion.  You will be 
monitored for side effects for 2 hours after the first LMB-100 infusion, and for 30 minutes after 
all other LMB-100 infusions if no side effects occurred previously.  You will be given standard 
pre-medications that include an antihistamine (such a Benadryl), acetaminophen (Tylenol) and 
ranitidine to help prevent infusion related side effects. Dexamethasone or an equivalent steroid 
may be added if you experience a reaction even after using the standard pre-medications. 
While you are taking study medication, we will perform a number of tests and examinations for 
safety and to test the effect of the study therapy: 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 4 of 14 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
These include routine blood and urine tests that will be on each day you receive an infusion, 
scans that will be performed approximately every 6 weeks, and ECGs that will be done on day 1 
of each cycle. 
In addition to the safety tests, we will also perform tests for research studies to find out how your 
body handles the drugs (PKs), how your body, including your immune system, reacts to the drug 
and how certain side effects of the LMB-100 might be caused. We will also conduct genetic 
studies focused on genes that process drugs, nab-paclitaxel in particular.  Most of the sampling 
for these research tests will be done before your first dose of study drug or on the days you take 
the study drug (just before or just after you get the study drug). In cycle 1, we will also collect 
samples on day 6 (may sometimes be done on day 5). In addition, on day 1 of cycle 1 samples 
will be drawn before your infusion and periodically for up to 72 hours (3 days) after the end of 
your nab-paclitaxel infusion. 
When you are finished taking the drugs 
Withdrawal Visit 
If you received 2 cycles of LMB-100, the following assessments will be performed at the end of 
cycle 2: 
x Medical history and physical examination 
x Routine blood and urine tests 
x Scans 
x Blood tests for tumor markers 
x ECG 
Safety Visit 
If you did not complete both cycles of the study drug, or if you have completed 2 cycles but the 
scans above showed that your disease has gotten worse, you will be asked to return to the NIH 
approximately 3 – 6 weeks after you have had last dose of study drug for a safety visit.  
If you completed cycle 2 and your scans did not reveal worsening disease, you will be asked to 
return approximately six weeks after your last scan for a restaging scan and safety visit. 
The visit will include the following tests: 
x Medical history and physical exam 
x Routine blood and urine tests including pregnancy test in women who can have children 
x ECG 
x Scans if your disease has not worsened since the beginning of the study 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 5 of 14 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Long term follow up 
If after the safety visit, your disease remains stable or improved, you will continue to be scanned 
every 6 weeks until your disease gets worse. 
About once a year, regardless of whether your disease has gotten worse, we will contact you or 
your physician by telephone to ask about any other cancer therapies you may have started and 
about your survival status. 
Birth Control 
If you are a woman who is breast feeding or pregnant, you may not take part in the study because 
we don’t know how this medicine would affect your baby or your unborn child. If you are a 
woman who can become pregnant, or are the partner of a woman who can become pregnant, you 
will need to practice an effective form of birth control before starting study treatment, during 
study treatment, and for 3 months after you finish study treatment.  In addition, male subjects 
should not donate sperm during the study and for 3 months after the last dose of study therapy. If 
you think that you or your partner is pregnant, you should tell your study doctor or nurse at once.   
Effective forms of birth control include:  
x abstinence  
x intrauterine device (IUD) 
x hormonal [birth control pills, injections, or implants] 
x tubal ligation 
x vasectomy 
Risks or Discomforts of Participation 
Risks and Possible Undesirable Effects of LMB-100 
Because LMB-100 is still being tested for safety, we do not know all of the possible side effects.  
However, below is a list of the most common and most serious side effects occurring on an 
earlier and ongoing studies, some occurring at higher doses than will be used in this study. 
The most common side effects (some were serious) were: 
x Low levels of the blood protein albumin which may lead to swelling, muscle weakness or 
loss of appetite 
x Tiredness 
x Swelling of the arms and legs 
x Nausea 
x Fever 
x Decreased appetite 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 6 of 14 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
x Shortness of breath 
x Pain in muscles  
x Reactions during or following the infusion of the drug which may cause fever, chills, rash 
or low blood pressure 
Less common, but serious side effects included: 
x Fluid in the organs which may cause low blood pressure, shortness of breath, swelling of 
ankles 
x Abnormal heartbeat 
x Pain in joints 
x Kidney damage which may cause swelling, may require dialysis 
Other possible side effects 
Other possible side effects discussed below are based on side effects that occurred when testing a 
similar agent, SS1P and also in animal studies of LMB-100.  It is possible that there may be 
other unexpected side-effects that occur in addition to those listed below. 
LMB-100 may cause inflammation to membranes causing chest pain, shortness of breath, low 
blood pressure, and heart failure.  In animals, some mild kidney toxicity was seen, characterized 
by increased enzymes and protein in the urine. This will be checked for with regular blood and 
urine tests. 
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. 
There may also be pain and swelling at the infusion site. 
It is important that you contact your doctor as soon as you experience any side effects whether 
you think the treatment has caused them or not.  You must also tell your doctor if you have 
started any new medication or had a change to your existing medication.  This includes 
medications available without a prescription (over the counter) and alternative medicines.  If you 
have any questions or concerns about any of the information provided above, about the possible 
side effects of treatment, or the possible consequences of treatment for those side effects, please 
ask the principal investigator or the research staff for more information.  
The most important symptoms you need to report to your doctor immediately are: 
o possible infusion or allergic reactions (symptoms that start during or within a few 
hours of the infusion, e.g. wheezing, tightness in the throat or chest, rash, and 
facial swelling) 
o chest pain 
o shortness of breath 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 7 of 14 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
o palpitations (fast heart beat) 
o bleeding and high fever 
o impaired brain function (e.g., dizziness, blurred vision, confusion) 
 
 
 
If you experience any severe or dangerous side effect, you should: 
1. Seek professional medical help immediately. 
2. Call your study doctor. 
3. If necessary, go to the nearest emergency room. 
 
Risks of nab-paclitaxel 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving nab-paclitaxel, more than 20 and up to 100 may have: 
x Anemia which may cause tiredness, or may require blood transfusions 
x Infection, especially when white blood cell count is low 
x Diarrhea, nausea, vomiting 
x Sores in mouth which may cause difficulty swallowing 
x Allergic reaction which may cause rash, low blood pressure, wheezing, shortness of breath, 
swelling of the face or throat 
x Bruising, bleeding 
x Pain 
x Muscle weakness 
x Numbness, tingling or pain of the arms and legs 
x Hair loss 
 
OCCASIONAL, SOME MAY BE SERIOUS 
In 100 people receiving nab-paclitaxel, from 4 to 20 may have: 
x Abnormal heartbeat 
x Damage to the lungs which may cause shortness of breath 
x Blood clot which may cause swelling, pain, shortness of breath 
 
 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 8 of 14 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
RARE, AND SERIOUS 
In 100 people receiving nab-paclitaxel, 3 or fewer may have: 
x Heart attack or heart failure which may cause shortness of breath, swelling of ankles, and 
tiredness 
x A tear or a hole in the stomach which may cause belly pain or that may require surgery 
 
Nab-paclitaxel may cause serious birth defects. Please refer to the section about birth control for 
more information on how to protect yourself if you are a female who is able to get pregnant or a 
male patient who has a partner who is able to get pregnant. Nab-paclitaxel can cause irreversible 
infertility in male patients. Male patients should seek advice on conservation of sperm prior to 
treatment. 
Risks from pre-medications 
Acetaminophen  
Acetaminophen is considered to be safe and effective in the recommended doses. However, 
when taken incorrectly acetaminophen can cause liver damage. Your risk of liver damage may 
be increased if you drink more than three alcoholic drinks every day, take more than the 
recommended dose (overdose), or if you take any additional drugs that also contain 
acetaminophen at the same time. 
Diphenhydramine 
Drowsiness, dizziness, constipation, stomach upset, blurred vision, or dry mouth/nose/throat may 
occur when taking diphenhydramine.Ranitidine:   
It can cause constipation, diarrhea, headache, nausea or upset stomach.  Rare serious side effects 
include severe allergic reaction with rash, hives, itching, difficulty breathing; confusion, dark 
urine, depression, fast or slow heartbeat, unusual bruising or bleeding, yellowing of the eyes or 
skin (indicating liver damage). 
Dexamethasone:   
Stomach upset, headache, dizziness, changes in your period, trouble sleeping, increased appetite, 
or weight gain may occur. Rarely patients using dexamethasone have experienced increased 
infection, bone/joint pain, thirst, increased urination, irregular heartbeat, eye pain, vision 
problems, black stools, vomit that looks like coffee grounds, puffy face, swelling of the feet and 
ankles, pain/redness/swelling of the arms or legs, tiredness, mood changes, unusual hair/skin 
growth, muscle cramps, weakness, easy bruising/bleeding, slow wound healing, thinning skin 
and seizures. 
Risks from Study Procedures 
The following study procedures and treatments may have risks and cause discomfort while you 
participate on this study: 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 9 of 14 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
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.  
ECGs 
The glue used to keep the electrodes in place during the ECG may irritate your skin and caused 
redness.  
Central Line Insertion 
x Contamination of the catheter which would result in a serious blood stream infection, 
requiring admission to the hospital and giving you antibiotics through the vein. 
x Collapsed lung particularly if the central line is placed in the vein under your collarbone. 
Collapsed lung is treated with a chest tube when necessary. 
x During the insertion of some types of central lines, the heart may be irritated by the 
process while the line travels through the blood vessels near the heart, causing an 
alteration in the heart's rhythm. This typically gets better once the line is in place but may 
require medication for some rare individuals. 
x Air embolism, a condition where air enters the blood stream and begins to travel through 
the body. This condition, which is very serious, is also very rare and largely preventable. 
Potential Benefits of Participation 
Are there benefits to taking part in this study?  
The aim of this study is to find a safe dose as well as to see if this experimental treatment will 
cause your tumors to shrink.  We do not know if you will receive personal, medical benefit from 
taking part in this study.  These potential benefits could include shrinking of your tumor or 
lessening of 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, although the knowledge gained from this study may help others in 
the future who have cancer.   
What other choices do I have if I do not take part in this study?  
Instead of being in this study, you have these options: 
x Getting treatment or care for your cancer without being in a study, including standard 
options such as nanoliposomal irinotecan (Onivyde) 
x Taking part in another study 
x Getting comfort care, also called palliative care.  This type of care helps reduce pain, 
tiredness, appetite problems and other problems caused by the cancer.  It does not treat 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 10 of 14 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
the cancer directly.  Instead, it tries to improve how you feel.  Comfort care tries to keep 
you as active and comfortable as possible. 
Please talk to your doctor about these and other options. 
Research Subject’s Rights 
What are the costs of taking part in this study?  
If you choose to take part in the study, the following will apply, in keeping with the NIH policy: 
x 
You will receive study treatment at no charge to you. This may include 
surgery, medicines, laboratory testing, x-rays or scans done at the 
Clinical Center, National Institutes of Health (NIH), or arranged for you 
by the research team to be done outside the Clinical Center, NIH if the 
study related treatment is not available at the NIH.  
x 
There are limited funds available to cover the cost of some tests and 
procedures performed outside the Clinical Center, NIH.  You may have 
to pay for these costs if they are not covered by your insurance company. 
x 
Medicines that are not part of the study treatment will not be provided or 
paid for by the Clinical Center, NIH. 
x 
Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
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: 
x The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), which are involved in keeping research safe for people. 
x NIH Intramural Institutional Review Board 
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.  
Certificate of Confidentiality  
To help us protect your privacy, we have obtained a Certificate of Confidentiality. The 
researchers can use this Certificate to legally refuse to disclose information that may identify you 
in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for 
example, if there is a court subpoena. The researchers will use the Certificate to resist any 
demands for information that would identify you, except as explained below. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 11 of 14 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
You should also know that there are several circumstances in which the Certificate does not 
provide coverage. These include when information:  
x will be used for auditing or program evaluation internally by the NIH; or  
x must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA).  
x is necessary for your medical treatment and you have consented to this disclosure;  
x is for other research.  
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible 
as evidence or used for any purpose in any action, suit, or proceeding without your consent.  
You should understand that a Certificate of Confidentiality does not prevent you or a member of 
your family from voluntarily releasing information about yourself or your involvement in this 
research. If an insurer, employer, or other person obtains your written consent to receive research 
information, then the researchers will not use the Certificate to withhold that information. 
The Certificate of Confidentiality will not protect against the required reporting by hospital staff 
of information on suspected child abuse, reportable communicable diseases, and/or possible 
threat of harm to self or others. 
Stopping Therapy  
Your doctor may decide to stop your therapy for the following reasons: 
x if he/she believes that it is in your best interest 
x if your disease comes back during treatment 
x if you become pregnant 
x if you have side effects from the treatment that your doctor thinks are too severe 
x if new information shows that another treatment would be better for you 
In this case, you will be informed of the reason therapy is being stopped. 
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. However, according to FDA guidelines, 
information collected on you up to that point may still be provided to collaborators or designated 
representatives. If you withdraw your consent and leave the trial, any samples of yours that have 
been obtained for the study and stored at the NCI can be destroyed upon request. However, any 
samples and data generated from the samples that have already been distributed to other 
researchers or placed in the research databases cannot be recalled and destroyed. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 12 of 14 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Conflict of Interest 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a Protocol Review Guide.  You may ask your research 
team for a copy of the Protocol Review Guide or for more information.  Members of the research 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study.  This is allowed under federal rules and is not a 
conflict of interest.  
The National Institutes of Health and the research team for this study have developed a drug 
being used in this study.  This means it is possible that the results of this study could lead to 
payments to NIH scientists and to the NIH. By law, government scientists are required to receive 
such payments for their inventions. You will not receive any money from the development of 
LMB-100 in combination with nab-paclitaxel.  
Use of Specimens and Data for Future Research 
To advance science, it is helpful for researchers to share information they get from studying 
human samples.  They do this by putting it into one or more scientific databases, where it is 
stored along with information from other studies. A researcher who wants to study the 
information must apply to the database and be approved.  Researchers use specimens and data 
stored in scientific databases to advance science and learn about health and disease.   
We plan to keep some of your specimens and data that we collect and use them for future 
research and share them with other researchers. We will not contact you to ask about each of 
these future uses.  These specimens and data will be stripped of identifiers such as name, address 
or account number, so that it may be used for future research on any topic and shared broadly for 
research purposes. Your specimens and data will be used for research purposes only and will not 
benefit you.  It is also possible that the stored specimens and data may never be used.  Results of 
research done on your specimens and data will not be available to you or your doctor.  It might 
help people who have cancer and other diseases in the future.   
If do not want your stored specimens and data used for future research, please contact us in 
writing and let us know that you do not want us to use your specimens and/or data.  Then any 
specimens that have not already been used or shared will be destroyed and your data will not be 
used for future research. However, it may not be possible to withdraw or delete materials or data 
once they have been shared with other researchers. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 16-C-0128 
CONTINUATION: page 13 of 14 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
OTHER PERTINENT INFORMATION 
1. 
Confidentiality.  When results of an NIH research study are reported in medical journals 
or at scientific meetings, the people who take part are not named and identified.  In most cases, 
the NIH will not release any information about your research involvement without your written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance 
company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration (FDA), 
members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
2. 
Policy Regarding Research-Related Injuries.  The 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 National Institutes of Health, the Clinical Center, or the Federal Government.  
However, you have the right to pursue legal remedy if you believe that your injury justifies such 
action. 
3. 
Payments.  The amount of payment to research volunteers is guided by the National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies at 
the National Institutes of Health.  Reimbursement of travel and subsistence will be offered 
consistent with NIH guidelines. 
4. 
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, Christine Alewine, M.D., Ph.D., Building 37, Room 5116, Telephone:  
240-760-6146. You may also call the Clinical Center Patient Representative at 301-496-2626. If 
you have any questions about the use of your specimens or data for future research studies, you 
may also contact the Office of the Clinical Director, Telephone:  240-760-6070. 
5. 
Consent Document.  Please keep a copy of this document in case you want to read it 
again. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 16-C-0128 
CONTINUATION: page 14 of 14 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
 
 
 
Signature of Adult Patient/ 
Legal Representative 
Date 
 
 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to 
participate in the study. 
 
  
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM AUGUST 31, 2020 THROUGH AUGUST 30, 2021. 
 
 
 
 
 
 
 
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name 
 

ICF_004.pdf: 
MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
INSTITUTE: 
National Cancer Institute 
STUDY NUMBER: 
16-C-0128 
PRINCIPAL INVESTIGATOR: 
Christine Alewine, M.D., Ph. D. 
STUDY TITLE:  
A Phase I/II Study of Mesothelin-Targeted Immunotoxin LMB-100 Alone or in 
Combination with Nab-Paclitaxel in Participants with Previously Treated Metastatic and/ 
or Locally Advanced Pancreatic Ductal Adenocarcinoma and Mesothelin Expressing 
Solid Tumors 
 
Continuing Review Approved by the IRB on 08/31/20 
Amendment Approved by the IRB on 12/13/18 (L) 
 
Date posted to web:  09/04/20 
Arm B1 (Continuous Infusion Single Agent Lead-in) 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent (2) 
 
INTRODUCTION 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
First, we want you to know that: 
Taking part in NIH research is entirely voluntary.  
You may choose not to take part, or you may withdraw from the study at any time.  In 
either case, you will not lose any benefits to which you are otherwise entitled.  However, 
to receive care at the NIH, you must be taking part in a study or be under evaluation for 
study participation. 
You may receive no benefit from taking part.  The research may give us knowledge that 
may help people in the future. 
Second, 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).  If you 
have such beliefs, please discuss them with your NIH doctors or research team before you agree 
to the study. 
Now we will describe this research study.  Before you decide to take part, please take as much 
time as you need to ask any questions and discuss this study with anyone at NIH, or with family, 
friends or your personal physician or other health professional.   
Why is this study being done?  
LMB-100 is an investigational agent, meaning that it has not been approved by the US Food and 
Drug Administration. It is a type of manufactured protein which is similar to protein normally 
produced by your body.  LMB-100 is attracted to the mesothelin protein, which is present on the 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 2 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
surface of many different tumors. The mesothelin protein is found in only a very small number 
of normal tissues.  After binding to the mesothelin on tumors, LMB-100 can then attack and kill 
cancer cells.  
Nab-paclitaxel is an FDA approved agent in the treatment of pancreatic cancer. It has not, 
however been tried in combination with LMB-100. 
This study, which is divided into multiple parts will determine a safe dose of LMB-100 on 
different administration schedules alone or in combination with a fixed dose of nab-paclitaxel in 
the phase 1 portion. 
x In phase 1, Arm A1 – subjects with pancreatic cancer will receive nab-paclitaxel in 
combination with LMB-100 given every other day for 3 days in each 21-day cycle. 
x In phase 1, Arm B1, (single Agent lead-in) – subjects that have tumors that test positive 
for mesothelin will receive LMB-100 alone for 1, 2, 3 or 4 days continuously or two 24-
hour infusions (days 1 and 4) depending on dose level in each 21-day cycle. 
x In phase 1, Arm B2, (combination therapy) – subjects with pancreatic cancer will receive 
nab-paclitaxel in combination with LMB-100 given for 1, 2, 3 or 4 days continuously or 
two 24-hour infusions (days 1 and 4) depending on dose level in each 21-day cycle.  
In the phase 2 portion of the study (Arm A2), we will determine whether the dose established in 
phase 1, Arm A1 reduces the size of tumors in patients with pancreatic cancer. 
You are participating in the phase 1, Arm B1 single agent lead-in portion of the study. Note: If 
you are a patient with pancreatic cancer, by taking part in this portion of the study, you are 
foregoing treatment with chemotherapy regimens that have been shown to increase survival in 
your disease. 
Why are you being asked to take part in this study? 
You are being asked to take part in this study because you have a cancer that expresses 
mesothelin that has worsened after anti-cancer therapy.  
How many people will take part in this study?  
Up to 100 participants will be enrolled in the study overall. 
Description of Research Study 
Participants will be enrolled in this portion of the study in groups of 3 to 6 at increasing doses or 
dose durations until a dose is reach where 2 or more participants experience intolerable side 
effects.  If no dose level is reached where 2 or more participants experience intolerable side 
effects, then the highest tested dose will be selected as the maximum tolerated dose (MTD).  If a 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 3 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
dose is reached where there are 2 or more intolerable side effects, the dose just below it will be 
selected as the MTD provided that no more than 1 of 6 participants experienced intolerable side 
effects at that dose.   
Depending on your assigned dose level, you will receive LMB-100 through an IV catheter (a 
tube inserted in a vein, usually in your arm) continuously for 24, 48, 72 or 96 hours on 1, 2, 3 or 
4 days of each cycle. Alternatively, you may receive two 24-hour infusions (days 1 and 4) during 
each cycle.  On the first day of each cycle, unless you are among the first 3 participants in this 
part of the study, you will also receive what is called a loading dose (lasting no more than 3 
hours) of LMB-100 before the start of the continuous infusion. You will have to stay in the 
hospital while you are receiving the infusion.  You will receive LMB-100 for up to 2 cycles or 
until your disease worsens or you have intolerable side effects, whichever happens first. We will 
continue to follow you after you have finished taking the study drug to keep track of your disease 
status (progression), your survival status or whether you have taken any additional cancer 
therapy.  The specific procedures you will have are described below. 
What will happen if you take part in this research 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 
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 are performed under a separate consent, include: 
x Confirmation of diagnosis (You must provide a sample tumor tissue for formal evaluation 
by the NCI Laboratory of Pathology.  The tissue may be from a previous surgery or 
biopsy.  If none is available, we will ask you to have a biopsy to provide a fresh sample).   
x Mesothelin testing.  Previously collected tissue from your tumor or any leftover tissue 
that may be collected for the confirmation of diagnosis will be used to determine whether 
your tumor cells have mesothelin, unless you have pancreatic cancer or a type of 
mesothelioma referred to as epithelioid. 
x Medical history and physical examination 
x Routine blood and urine tests including pregnancy test in women who can have children.  
Pregnant women will not be allowed on study. 
x Scans  
x Electrocardiogram (ECG) 
x Echocardiogram 
x Blood for tumor markers 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 4 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
During the study 
Once it is determined that you are eligible and you have signed this consent, you will receive IV 
infusions of LMB-100 as described above. Depending on your assigned dose level each LMB-
100 infusion will last for 24 hours (1 day), 48 hours (2 days), 72 hours (3 days) or 96 hours (4 
days) or 24 hours each on day 1 and day 4 and will be given through a central line (an IV tube 
placed in a large vein for long term therapy) or through a mediport if you already have one 
installed.  As indicated above, a short loading dose may also be given. You will be monitored for 
side effects during each LMB-100 infusion. You will be given standard pre-medications that 
include an antihistamine (such a Benadryl), acetaminophen (Tylenol) and ranitidine to help 
prevent infusion related side effects. Dexamethasone or an equivalent steroid may be added if 
you experience a reaction even after using the standard pre-medications. 
While you are taking study medication, we will perform a number of tests and examinations for 
safety and to test the effect of the study therapy: 
These include routine blood and urine tests that will be on each day you receive an infusion, 
scans that will be performed approximately every 6 weeks, and ECGs that will be done while 
you are receiving LMB-100. 
In addition to the safety tests, we will also perform tests for research studies to find out how your 
body handles the LMB-100 (PKs), how your body, including your immune system, reacts to the 
drug and how certain side effects of the LMB-100 might be caused. We will also conduct genetic 
studies focused on genes that process drugs, nab-paclitaxel in particular.  Most of the sampling 
for these research tests will be done before your first dose of study drug or on the days you take 
the study drug just before or during the infusion.  A sample will also be drawn about 2 hours 
after the end of infusion in cycle 1. 
An optional biopsy may also be collected after you have received 2 cycles of study therapy.  The 
biopsies to be performed are 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 sample collected at the time of each biopsy.  All tissue will be reviewed by the NCI 
Laboratory of Pathology. Please see page 9, Tumor Biopsies and Effusions for the risks of a 
biopsy. 
When you are finished taking the drugs 
Withdrawal Visit 
If you received 2 cycles of LMB-100, the following assessments will be performed at the end of 
cycle 2: 
x Medical history and physical examination 
x Routine blood and urine tests 
x Scans 
x Blood tests for tumor markers 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 5 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
x ECG 
Safety Visit 
If you did not complete both cycles of the study drug, or if you have completed 2 cycles but the 
scans above showed that your disease has gotten worse, you will be asked to return to the NIH 
approximately 3 – 6 weeks after you have had last dose of study drug for a safety visit.  
If you completed cycle 2 and your scans did not reveal worsening disease, you will be asked to 
return approximately six weeks after your last scan for a restaging scan and safety visit. 
The visit will include the following tests: 
x Medical history and physical exam 
x Routine blood and urine tests including pregnancy test in women who can have children 
x ECG 
x Scans if your disease has not worsened since the beginning of the study 
Long term follow up 
If after the safety visit, your disease remains stable or improved, you will continue to be scanned 
every 6 weeks until your disease gets worse. 
About once a year, regardless of whether your disease has gotten worse, we will contact you or 
your physician by telephone to ask about any other cancer therapies you may have started and 
about your survival status. 
Birth Control 
If you are a woman who is breast feeding or pregnant, you may not take part in the study because 
we don’t know how this medicine would affect your baby or your unborn child. If you are a 
woman who can become pregnant, or are the partner of a woman who can become pregnant, you 
will need to practice an effective form of birth control before starting study treatment, during 
study treatment, and for 3 months after you finish study treatment.  In addition, male subjects 
should not donate sperm during the study and for 3 months after the last dose of study therapy. If 
you think that you or your partner is pregnant, you should tell your study doctor or nurse at once.   
Effective forms of birth control include:  
x abstinence  
x intrauterine device (IUD) 
x hormonal [birth control pills, injections, or implants] 
x tubal ligation 
x vasectomy 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 6 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Risks or Discomforts of Participation 
Risks and Possible Undesirable Effects of LMB-100 
Because LMB-100 is still being tested for safety, we do not know all of the possible side effects.  
However, below is a list of the most common and most serious side effects occurring on an 
earlier and ongoing studies, some occurring at higher doses than will be used in this study. 
The most common side effects (some were serious) were: 
x Low levels of the blood protein albumin which may lead to swelling, muscle weakness or 
loss of appetite 
x Tiredness 
x Swelling of the arms and legs 
x Nausea 
x Fever 
x Decreased appetite 
x Shortness of breath 
x Pain in muscles  
x Reactions during or following the infusion of the drug which may cause fever, chills, rash 
or low blood pressure 
Less common, but serious side effects included: 
x Fluid in the organs which may cause low blood pressure, shortness of breath, swelling of 
ankles 
x Abnormal heartbeat 
x Pain in joints 
x Kidney damage which may cause swelling, may require dialysis 
Other possible side effects 
Other possible side effects discussed below are based on side effects that occurred when testing a 
similar agent, SS1P and also in animal studies of LMB-100.  It is possible that there may be 
other unexpected side-effects that occur in addition to those listed below. 
LMB-100 may cause inflammation to membranes causing chest pain, shortness of breath, low 
blood pressure, and heart failure.  In animals, some mild kidney toxicity was seen, characterized 
by increased enzymes and protein in the urine. This will be checked for with regular blood and 
urine tests. 
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 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 7 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
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. 
There may also be pain and swelling at the infusion site. 
It is important that you contact your doctor as soon as you experience any side effects whether 
you think the treatment has caused them or not.  You must also tell your doctor if you have 
started any new medication or had a change to your existing medication.  This includes 
medications available without a prescription (over the counter) and alternative medicines.  If you 
have any questions or concerns about any of the information provided above, about the possible 
side effects of treatment, or the possible consequences of treatment for those side effects, please 
ask the principal investigator or the research staff for more information.  
The most important symptoms you need to report to your doctor immediately are: 
o possible infusion or allergic reactions (symptoms that start during or within a few 
hours of the infusion, e.g. wheezing, tightness in the throat or chest, rash, and 
facial swelling) 
o chest pain 
o shortness of breath 
o palpitations (fast heart beat) 
o bleeding and high fever 
o impaired brain function (e.g., dizziness, blurred vision, confusion) 
 
 
If you experience any severe or dangerous side effect, you should: 
1. Seek professional medical help immediately. 
2. Call your study doctor. 
3. If necessary, go to the nearest emergency room. 
 
Risks from pre-medications 
Acetaminophen  
Acetaminophen is considered to be safe and effective in the recommended doses. However, 
when taken incorrectly acetaminophen can cause liver damage. Your risk of liver damage may 
be increased if you drink more than three alcoholic drinks every day, take more than the 
recommended dose (overdose), or if you take any additional drugs that also contain 
acetaminophen at the same time. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 8 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
Diphenhydramine 
Drowsiness, dizziness, constipation, stomach upset, blurred vision, or dry mouth/nose/throat may 
occur when taking diphenhydramine.Ranitidine:   
It can cause constipation, diarrhea, headache, nausea or upset stomach.  Rare serious side effects 
include severe allergic reaction with rash, hives, itching, difficulty breathing; confusion, dark 
urine, depression, fast or slow heartbeat, unusual bruising or bleeding, yellowing of the eyes or 
skin (indicating liver damage). 
Dexamethasone:   
Stomach upset, headache, dizziness, changes in your period, trouble sleeping, increased appetite, 
or weight gain may occur. Rarely patients using dexamethasone have experienced increased 
infection, bone/joint pain, thirst, increased urination, irregular heartbeat, eye pain, vision 
problems, black stools, vomit that looks like coffee grounds, puffy face, swelling of the feet and 
ankles, pain/redness/swelling of the arms or legs, tiredness, mood changes, unusual hair/skin 
growth, muscle cramps, weakness, easy bruising/bleeding, slow wound healing, thinning skin 
and seizures. 
Risks from Study Procedures 
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.  
ECGs 
The glue used to keep the electrodes in place during the ECG may irritate your skin and caused 
redness.  
Central Line Insertion 
x Contamination of the catheter which would result in a serious blood stream infection, 
requiring admission to the hospital and giving you antibiotics through the vein. 
x Collapsed lung particularly if the central line is placed in the vein under your collarbone. 
Collapsed lung is treated with a chest tube when necessary. 
x During the insertion of some types of central lines, the heart may be irritated by the 
process while the line travels through the blood vessels near the heart, causing an 
alteration in the heart's rhythm. This typically gets better once the line is in place but may 
require medication for some rare individuals. 
x Air embolism, a condition where air enters the blood stream and begins to travel through 
the body. This condition, which is very serious, is also very rare and largely preventable. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 9 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
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, infection or of an allergic reaction to 
the anesthetic agent used to anesthetize the skin at the biopsy site.  Once the sample has been 
obtained, a stitch may be used to close the wound and assist in healing.  
In some cases, we may use CT scans to help guide us during your tumor biopsy.  This introduces 
the added risk of research radiation.  This research study may involve exposure to radiation from 
up to 1 CT guided research biopsy.  This radiation exposure is not required for your medical care 
and is for research purposes only. The amount of radiation you will receive in this study is 0.77 
rem which is below the guideline of 5 rem per year allowed for research subjects by the NIH 
Radiation Safety Committee.  The average person in the United States receives a radiation 
exposure of 0.3 rem per year from natural sources, such as the sun, outer space, and the earth's 
air and soil.  If you would like more information about radiation, please ask the investigator for a 
copy of the pamphlet, An Introduction to Radiation for NIH Research Subjects. 
While there is no direct evidence that the amount of exposure received from participating in 
this study is harmful, there is indirect evidence it may not be completely safe.  There may 
be a very slight increase in the risk of cancer.  
Please tell your doctor if you have had any radiation exposure in the past year, either from 
other research studies or from medical tests or care, so we can make sure that you will not 
receive too much radiation. Radiation exposure includes x-rays taken in radiology 
departments, cardiac catheterization, and fluoroscopy as well as nuclear medicine scans in 
which radioactive materials were injected into your body.  
Potential Benefits of Participation 
Are there benefits to taking part in this study?  
The aim of this study is to find a safe dose as well as to see if this experimental treatment will 
cause your tumors to shrink.  We do not know if you will receive personal, medical benefit from 
taking part in this study.  These potential benefits could include shrinking of your tumor or 
lessening of 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, although the knowledge gained from this study may help others in 
the future who have cancer.   


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 10 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
What other choices do I have if I do not take part in this study?  
Instead of being in this study, you have these options: 
x Getting treatment or care for your cancer without being in a study, including standard 
options  
x Taking part in another study 
x Getting comfort care, also called palliative care.  This type of care helps reduce pain, 
tiredness, appetite problems and other problems caused by the cancer.  It does not treat 
the cancer directly.  Instead, it tries to improve how you feel.  Comfort care tries to keep 
you as active and comfortable as possible. 
Please talk to your doctor about these and other options. 
Research Subject’s Rights 
What are the costs of taking part in this study?  
If you choose to take part in the study, the following will apply, in keeping with the NIH policy: 
x 
You will receive study treatment at no charge to you. This may include 
surgery, medicines, laboratory testing, x-rays or scans done at the 
Clinical Center, National Institutes of Health (NIH), or arranged for you 
by the research team to be done outside the Clinical Center, NIH if the 
study related treatment is not available at the NIH.  
x 
There are limited funds available to cover the cost of some tests and 
procedures performed outside the Clinical Center, NIH.  You may have 
to pay for these costs if they are not covered by your insurance company. 
x 
Medicines that are not part of the study treatment will not be provided or 
paid for by the Clinical Center, NIH. 
x 
Once you have completed taking part in the study, medical care will no 
longer be provided by the Clinical Center, NIH. 
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: 
x The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), which are involved in keeping research safe for people. 
x NIH Intramural Institutional Review Board 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 11 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
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.  
Certificate of Confidentiality  
To help us protect your privacy, we have obtained a Certificate of Confidentiality. The 
researchers can use this Certificate to legally refuse to disclose information that may identify you 
in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for 
example, if there is a court subpoena. The researchers will use the Certificate to resist any 
demands for information that would identify you, except as explained below. 
You should also know that there are several circumstances in which the Certificate does not 
provide coverage. These include when information:  
x will be used for auditing or program evaluation internally by the NIH; or  
x must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA).  
x is necessary for your medical treatment and you have consented to this disclosure;  
x is for other research.  
In addition, identifiable, sensitive information protected by this Certificate cannot be admissible 
as evidence or used for any purpose in any action, suit, or proceeding without your consent.  
You should understand that a Certificate of Confidentiality does not prevent you or a member of 
your family from voluntarily releasing information about yourself or your involvement in this 
research. If an insurer, employer, or other person obtains your written consent to receive research 
information, then the researchers will not use the Certificate to withhold that information. 
The Certificate of Confidentiality will not protect against the required reporting by hospital staff 
of information on suspected child abuse, reportable communicable diseases, and/or possible 
threat of harm to self or others. 
Stopping Therapy  
Your doctor may decide to stop your therapy for the following reasons: 
x if he/she believes that it is in your best interest 
x if your disease comes back during treatment 
x if you become pregnant 
x if you have side effects from the treatment that your doctor thinks are too severe 
x if new information shows that another treatment would be better for you 
In this case, you will be informed of the reason therapy is being stopped. 


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 12 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
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. However, according to FDA guidelines, 
information collected on you up to that point may still be provided to collaborators or designated 
representatives. If you withdraw your consent and leave the trial, any samples of yours that have 
been obtained for the study and stored at the NCI can be destroyed upon request. However, any 
samples and data generated from the samples that have already been distributed to other 
researchers or placed in the research databases cannot be recalled and destroyed. 
Conflict of Interest 
The National Institutes of Health (NIH) reviews NIH staff researchers at least yearly for conflicts 
of interest.  This process is detailed in a Protocol Review Guide.  You may ask your research 
team for a copy of the Protocol Review Guide or for more information.  Members of the research 
team who do not work for NIH are expected to follow these guidelines but they do not need to 
report their personal finances to the NIH. 
Members of the research team working on this study may have up to $15,000 of stock in the 
companies that make products used in this study.  This is allowed under federal rules and is not a 
conflict of interest.  
The National Institutes of Health and the research team for this study have developed a drug 
being used in this study.  This means it is possible that the results of this study could lead to 
payments to NIH scientists and to the NIH. By law, government scientists are required to receive 
such payments for their inventions. You will not receive any money from the development of 
LMB-100 in combination with nab-paclitaxel.  
Use of Specimens and Data for Future Research 
To advance science, it is helpful for researchers to share information they get from studying 
human samples.  They do this by putting it into one or more scientific databases, where it is 
stored along with information from other studies. A researcher who wants to study the 
information must apply to the database and be approved.  Researchers use specimens and data 
stored in scientific databases to advance science and learn about health and disease.   
We plan to keep some of your specimens and data that we collect and use them for future 
research and share them with other researchers. We will not contact you to ask about each of 
these future uses.  These specimens and data will be stripped of identifiers such as name, address 
or account number, so that it may be used for future research on any topic and shared broadly for 
research purposes. Your specimens and data will be used for research purposes only and will not 
benefit you.  It is also possible that the stored specimens and data may never be used.  Results of 
research done on your specimens and data will not be available to you or your doctor.  It might 
help people who have cancer and other diseases in the future.   


MEDICAL RECORD 
CONTINUATION SHEET for either: 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
STUDY NUMBER:   16-C-0128  
CONTINUATION: page 13 of 15 pages 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
NIH-2514-1 (07-09) 
NIH-2514-2 (10-84) 
P.A.:  09-25-0099 
File in Section 4:  Protocol Consent 
 
If do not want your stored specimens and data used for future research, please contact us in 
writing and let us know that you do not want us to use your specimens and/or data.  Then any 
specimens that have not already been used or shared will be destroyed and your data will not be 
used for future research. However, it may not be possible to withdraw or delete materials or data 
once they have been shared with other researchers. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 16-C-0128 
CONTINUATION: page 14 of 15 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
OTHER PERTINENT INFORMATION 
1. 
Confidentiality.  When results of an NIH research study are reported in medical journals 
or at scientific meetings, the people who take part are not named and identified.  In most cases, 
the NIH will not release any information about your research involvement without your written 
permission.  However, if you sign a release of information form, for example, for an insurance 
company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance 
company to sell you insurance. 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you 
should know that the Act allows release of some information from your medical record without 
your permission, for example, if it is required by the Food and Drug Administration (FDA), 
members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
2. 
Policy Regarding Research-Related Injuries.  The 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 National Institutes of Health, the Clinical Center, or the Federal Government.  
However, you have the right to pursue legal remedy if you believe that your injury justifies such 
action. 
3. 
Payments.  The amount of payment to research volunteers is guided by the National 
Institutes of Health policies.  In general, patients are not paid for taking part in research studies at 
the National Institutes of Health.  Reimbursement of travel and subsistence will be offered 
consistent with NIH guidelines. 
4. 
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, Christine Alewine, M.D., Ph.D., Building 37, Room 5116, Telephone:  
240-760-6146. You may also call the Clinical Center Patient Representative at 301-496-2626. If 
you have any questions about the use of your specimens or data for future research studies, you 
may also contact the Office of the Clinical Director, Telephone:  240-760-6070. 
5. 
Consent Document.  Please keep a copy of this document in case you want to read it 
again. 


MEDICAL RECORD 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
• 
Adult Patient or 
• Parent, for Minor Patient 
STUDY NUMBER: 16-C-0128 
CONTINUATION: page 15 of 15 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH 
STUDY (Continuation Sheet) 
• Adult Patient or 
• Parent, for Minor Patient 
NIH-2514-1 (07-09) 
P.A.:  09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby consent to 
take part in this study. 
I have read the explanation about this study 
and have been given the opportunity to discuss 
it and to ask questions.  I hereby give 
permission for my child to take part in this 
study.   
(Attach NIH 2514-2, Minor’s Assent, if 
applicable.) 
 
  
  
 
 
 
Signature of Adult Patient/ 
Legal Representative 
Date 
 
 
Signature of Parent(s)/ Guardian Date 
 
 
Print Name 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to 
participate in the study. 
 
  
  
 
Signature of Parent(s)/Guardian 
Date 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM AUGUST 31, 2020 THROUGH AUGUST 30, 2021. 
 
 
 
 
 
 
 
 
Signature of Investigator 
Date 
Signature of Witness 
Date 
 
 
Print Name 
 
 
Print Name