Clinical trial NCT03801915
Conditions: Colon Cancer Pancreatic Cancer Cholangiocarcinoma Metastatic Colon Carcinoma Liver Metastasis
Keywords: Well Tolerated Agent Pancreas and Liver Resections Recurrence-Free Survival
Sponsor: National Cancer Institute (NCI)
Start date: 2019-11-13; Completion date: 2022-05-27
Enrollment: 10 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Background:

Gastrointestinal tumors have a molecule called carbohydrate antigen 19-9 (CA19-9) in the tumors and blood. The agent MVT-5873 was designed to block this molecule. Researchers want to test how safe it is to give this agent to people before and after surgery to remove a tumor. They want to learn the highest dose tolerated. They want to see if getting the agent at surgery helps slow down the disease.

Objective:

To test the safety of giving MVT-5873 at surgery to remove cancer and see if it slows the progression of the disease.

Eligibility:

Adults at least 18 years old with certain cancers and certain blood CA19-9 levels

Design:

Participants will be screened with:

* Medical history
* Physical exam
* Blood and heart tests
* Scans
* Review of normal activities
* Review of tumor sample
* Pregnancy test

A few days before surgery, participants will get a dose of the study agent. They will get it through a small plastic tube in a vein over about 2 hours.

Participants will sign a separate consent and have the surgery. A sample of the tumor and normal liver will be removed for research.

For 1-2 weeks after surgery, participants will recover in intensive care then regular care at the hospital. They will be monitored and treated throughout the stay.

After leaving the hospital, participants will get the study agent every week for 1 month. Then they will get it every other week for 2 months. They will repeat screening tests at study visits and at a follow-up visit. That will be about 5 weeks after the last dose.

Detailed description:
Background:

* Resections to remove tumors in the liver, bile ducts and pancreas are rarely curative, and patients frequently succumb to disease recurrence in the ensuing months to year(s) after the operation.
* Standard adjuvant therapies, which typically begin 6-12 weeks after surgery, offer little demonstrable decreases in the rates of tumor recurrence.
* The concept and implementation of immediate perioperative therapy has not been evaluated given the serious concerns related to healing and recovery with standard cytotoxic chemotherapy and newer targeted agents.
* A significant percentage of metastatic colorectal cancers, and primary tumors of the pancreas and bile ducts express Sialyl Lewis, an epitope on the well-established tumor marker, Carbohydrate antigen 19-9 (CA19-9).
* MVT-5873, a fully human antibody against Sialyl Lewis, has displayed antibody-dependent cell-mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) in vitro, potentiated chemotherapeutic efficacy in mouse models and demonstrated efficacy in Phase 1 trials of patients with advanced inoperable Hepato-pancreato-biliary (HPB) cancers.
* MVT-5873 is well tolerated as a single agent; moderate elevations in aspartate aminotransferase (AST)/alanine aminotransferase (ALT) appear to be dose-limiting.
* Patients with resectable Sialyl Lewis-expressing cancers represent an ideal population to explore the use of perioperative MVT-5873 given moderate level of CA 19-9 elevations, and the potential for extension of recurrence-free survival.

Objectives:

* Document the safety of perioperative MVT-5873 in patients undergoing pancreas and liver resections.
* Determine if perioperative MVT-5873 can decrease 1-year recurrence rates for patients with operable CA 19-9-producing cancers.

Eligibility:

* Histologically or cytologically confirmed adenocarcinoma of the

  * Colon (metastatic to liver)
  * Pancreas
  * Bile Ducts (Cholangiocarcinoma)
* Serum CA19-9 levels greater than the upper limit of normal, but less than 2500.
* Disease amenable to complete surgical extirpation.

Design:

-Pre-operative one-time treatment with MVT-5873, resection to remove all demonstrable disease in the liver, bile ducts and pancreas, and continuing MVT-5873 mono-therapy until off treatment criteria are met.

Arms: arm 1: Pre-operative escalation doses of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment arm 2: Pre-operative RD of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment
Interventions: intervention 1: MVT-5873 intervention 2: pancreatectomy or hepatectomy
Intervention descriptions: intervention 1: 1 mg/kg or 3 mg/kg for pre-operative dose, 1 mg/kg during post-operative period intervention 2: Pancreatectomy or hepatectomy

Protocol documents:
Prot_SAP_000.pdf: 
Abbreviated Title: Perioperative MVT-5873 
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Abbreviated Title: Perioperative MVT-5873  
CC Protocol #: 19C0039 E 
Version Date: 08/10/2020 
NCT Number #: NCT03801915 
Title: Perioperative MVT-5873, a Fully Human Monoclonal Antibody Against a CA 19-9 Epitope, 
for Operable CA 19-9 Producing Pancreatic Cancers, Cholangiocarcinomas, and Metastatic 
Colorectal Cancers 
 
NCI Principal Investigator: 
Jonathan M. Hernandez, MD  
Surgical Oncology Program (SOP), CCR, NCI 
Building 10, Room 4W-3740 
10 Center Drive  
Bethesda, MD 20892 
Phone: 240-760-6072 
E-mail: jonathan.hernandez@nih.gov  
 
 
 
Investigational Agents:    
Drug Name: 
HuMab-5B1 (MVT-5873) 
IND Number: 
144112 
Sponsor: 
NCI Center for Cancer Research  
Manufacturer: 
AAIPharma  
 
Commercial Agents: None  


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PRÉCIS 
Background: 
• Resections to remove tumors in the liver, bile ducts and pancreas are rarely curative, and 
patients frequently succumb to disease recurrence in the ensuing months to year(s) after 
the operation. 
• Standard adjuvant therapies, which typically begin 6-12 weeks after surgery, offer little 
demonstrable decreases in the rates of tumor recurrence.  
• The concept and implementation of immediate perioperative therapy has not been 
evaluated given the serious concerns related to healing and recovery with standard 
cytotoxic chemotherapy and newer targeted agents. 
• A significant percentage of metastatic colorectal cancers, and primary tumors of the 
pancreas and bile ducts express Sialyl Lewisa, an epitope on the well-established tumor 
marker, CA 19-9.  
• MVT-5873, a fully human antibody against Sialyl Lewisa, has displayed ADCC and CDC 
in vitro, potentiated chemotherapeutic efficacy in mouse models and demonstrated efficacy 
in Phase 1 trials of patients with advanced inoperable HPB cancers.  
• MVT-5873 is well tolerated as a single agent; moderate elevations in AST/ALT appear to 
be dose-limiting.   
• Patients with resectable Sialyl Lewisa-expressing cancers represent an ideal population to 
explore the use of perioperative MVT-5873 given moderate level of CA 19-9 elevations, 
and the potential for extension of recurrence-free survival. 
 
Objectives: 
• Document the safety of perioperative MVT-5873 in patients undergoing pancreas and liver 
resections. 
• Determine if perioperative MVT-5873 can decrease 1-year recurrence rates for patients 
with operable CA 19-9-producing cancers. 
 
Eligibility: 
• Histologically or cytologically confirmed adenocarcinoma of the 
o Colon (metastatic to liver) 
o Pancreas  
o Bile Ducts (Cholangiocarcinoma)  
• Serum CA 19-9 levels greater than the upper limit of normal, but less than 2500.  
• Disease amenable to complete surgical extirpation.   
 
Design:  
• Pre-operative one-time treatment with MVT-5873, resection to remove all demonstrable 
disease in the liver, bile ducts and pancreas, and continuing MVT-5873 mono-therapy until 
off treatment criteria are met. 


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TABLE OF CONTENTS 
PRÉCIS ........................................................................................................................................... 2 
TABLE OF CONTENTS ................................................................................................................ 3 
LIST OF TABLES .......................................................................................................................... 8 
LIST OF FIGURES ........................................................................................................................ 8 
1 
INTRODUCTION ................................................................................................................ 10 
 
Study Objectives ............................................................................................................ 10 
1.1.1 
Primary Objectives.................................................................................................. 10 
1.1.2 
Secondary Objective ............................................................................................... 10 
1.1.3 
Exploratory Objectives ........................................................................................... 10 
 
Background and Rationale ............................................................................................. 10 
1.2.1 
HPB Cancers ........................................................................................................... 10 
1.2.2 
Sialyl Lewis A Antigen - CA19-9 .......................................................................... 11 
1.2.3 
MVT-5873 .............................................................................................................. 12 
1.2.4 
Preclinical Studies ................................................................................................... 12 
1.2.5 
Effects in Humans ................................................................................................... 23 
1.2.6 
Pharmacokinetics .................................................................................................... 32 
1.2.7 
Reductions in Serum CA19-9 Levels ..................................................................... 32 
1.2.8 
Responses to Therapy ............................................................................................. 33 
1.2.9 
Rationale ................................................................................................................. 35 
1.2.10 Metastasis Assays Using Ex Vivo Perfusion of Omentum...................................... 36 
1.2.11 Ex Vivo Hepatic Perfusion Model ........................................................................... 36 
1.2.12 Simulated Metastasis Assay with Relevant Tissue (SMART) Chamber ................ 37 
1.2.13 The SMART System ............................................................................................... 37 
2 
ELIGIBILITY ASSESSMENT AND ENROLLMENT ....................................................... 40 
 
Eligibility Criteria .......................................................................................................... 40 
2.1.1 
Inclusion Criteria .................................................................................................... 40 
2.1.2 
Exclusion Criteria ................................................................................................... 42 
2.1.3 
Recruitment Strategies ............................................................................................ 42 
 
Screening Evaluation...................................................................................................... 43 
2.2.1 
Screening Activities Performed Prior to Obtaining Informed Consent .................. 43 
2.2.2 
Screening Activities Performed After a Consent for Screening Has Been Signed . 43 


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Participant Registration and Status Update Procedures ................................................. 44 
2.3.1 
Treatment Assignment and Randomization/Stratification Procedures ................... 44 
 
Baseline Evaluation ........................................................................................................ 45 
3 
STUDY IMPLEMENTATION ............................................................................................ 45 
 
Study Design .................................................................................................................. 45 
3.1.1 
Dose Limiting Toxicity ........................................................................................... 46 
3.1.2 
Safety Lead-In Cohorts ........................................................................................... 46 
3.1.3 
Treatment Cohorts .................................................................................................. 48 
 
Study Drug Administration ............................................................................................ 50 
3.2.1 
Preparation and Administration of MVT-5873....................................................... 50 
3.2.2 
Stability of MVT-5873 Following Preparation....................................................... 50 
3.2.3 
Upper Limit to Administered Dose in Obese Subjects ........................................... 50 
3.2.4 
Infusion Rate of MVT-5873 ................................................................................... 50 
3.2.5 
Treatment Guidelines for MVT-5873-Related Infusion Reaction .......................... 51 
3.2.6 
Premedication ......................................................................................................... 51 
 
Dose Modifications ........................................................................................................ 52 
 
Study Calendar ............................................................................................................... 54 
 
Surgical Guidelines ........................................................................................................ 57 
3.5.1 
Preoperative Patient Management .......................................................................... 57 
3.5.2 
Patient Management in the Operating Room .......................................................... 57 
3.5.3 
Postoperative Care .................................................................................................. 58 
3.5.4 
Discharge ................................................................................................................ 58 
 
Pathological Evaluation.................................................................................................. 58 
 
Criteria for Removal from Protocol Therapy and Off Study Criteria ............................ 59 
3.7.1 
Criteria for Removal from Protocol Therapy.......................................................... 59 
3.7.2 
Off-Study Criteria ................................................................................................... 60 
4 
CONCOMITANT MEDICATIONS/MEASURES .............................................................. 60 
5 
BIOSPECIMEN COLLECTION .......................................................................................... 60 
 
Specimen Collection Table ............................................................................................ 60 
 
Correlative Studies for Research/Pharmacokinetic Studies ........................................... 62 
5.2.1 
Tumor and Tissue Collection .................................................................................. 62 
5.2.2 
RNA Evaluation ...................................................................................................... 62 


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5.2.3 
Metastasis Assays Using Ex Vivo Perfusion of Omentum...................................... 63 
5.2.4 
Ex Vivo Hepatic Perfusion Model ........................................................................... 63 
5.2.5 
Circulating Tumor Cell Evaluation ......................................................................... 63 
5.2.6 
Monocyte Phagocyte System (MPS) Profiling ....................................................... 64 
 
Sample Storage, Tracking and Disposition .................................................................... 64 
5.3.1 
Samples Managed by the Blood Processing Core (BPC) ....................................... 64 
5.3.2 
Procedures for Storage of Patient Samples in the Laboratory of Dr. Trepel .......... 65 
5.3.3 
Procedures for Storage of Tissue Specimens in the Laboratory of Pathology ....... 66 
5.3.4 
Procedures for Storage of Patient Samples in the Laboratory of Dr. Hernandez ... 66 
5.3.5 
Protocol Completion/Sample Destruction .............................................................. 66 
5.3.6 
A Certificate of Confidentiality .............................................................................. 67 
5.3.7 
Management of Results........................................................................................... 67 
5.3.8 
Genetic Counseling ................................................................................................. 67 
6 
DATA COLLECTION AND EVALUATION ..................................................................... 67 
 
Data Collection ............................................................................................................... 67 
6.1.1 
Routine Data Collection .......................................................................................... 68 
 
Data Sharing Plans ......................................................................................................... 69 
6.2.1 
Human Data Sharing Plan ....................................................................................... 69 
6.2.2 
Genomic Data Sharing Plan .................................................................................... 70 
 
Response Criteria ........................................................................................................... 70 
6.3.1 
Definitions............................................................................................................... 70 
6.3.2 
Disease Parameters ................................................................................................. 70 
6.3.3 
Methods for Evaluation of Measurable Disease ..................................................... 71 
6.3.4 
Response Criteria .................................................................................................... 73 
6.3.5 
Duration of Response .............................................................................................. 76 
6.3.6 
Progression-Free Survival ....................................................................................... 76 
 
Toxicity Criteria ............................................................................................................. 76 
7 
NIH REPORTING REQUIREMENTS / DATA AND SAFETY MONITORING PLAN .. 76 
 
Definitions ...................................................................................................................... 76 
 
OHSRP Office of Compliance and Training / IRB Reporting ....................................... 76 
7.2.1 
Expedited Reporting ............................................................................................... 76 
7.2.2 
IRB Requirements for PI Reporting at Continuing Review ................................... 77 


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NCI Clinical Director Reporting .................................................................................... 77 
 
NIH Required Data and Safety Monitoring Plan ........................................................... 77 
7.4.1 
Principal Investigator/Research Team .................................................................... 77 
8 
SPONSOR SAFETY REPORTING ..................................................................................... 77 
 
Definitions ...................................................................................................................... 77 
8.1.1 
Adverse Event ......................................................................................................... 77 
8.1.2 
Serious Adverse Event (SAE) ................................................................................. 78 
8.1.3 
Life-threatening....................................................................................................... 78 
8.1.4 
Severity ................................................................................................................... 78 
8.1.5 
Relationship to Study Product ................................................................................ 78 
 
Assessment of Safety Events.......................................................................................... 79 
 
Reporting of Serious Adverse Events ............................................................................ 79 
 
Reporting Pregnancy ...................................................................................................... 79 
8.4.1 
Maternal Exposure ................................................................................................. 79 
8.4.2 
Paternal Exposure ................................................................................................... 80 
 
Regulatory Reporting for Studies Conducted Under CCR-Sponsored IND .................. 80 
9 
CLINICAL MONITORING ................................................................................................. 80 
10 STATISTICAL CONSIDERATIONS.................................................................................. 81 
 
Statistical Hypotheses ................................................................................................. 81 
10.1.1 Primary Efficacy Endpoints .................................................................................... 81 
10.1.2 Secondary Efficacy Endpoints ................................................................................ 81 
 
Sample Size Determination: ....................................................................................... 81 
 
Populations for Analysis ............................................................................................. 82 
10.3.1 Evaluable for Toxicity ............................................................................................ 83 
10.3.2 Evaluable for Objective Response .......................................................................... 83 
10.3.3 Evaluable Non-Target Disease Response ............................................................... 83 
 
Statistical Analyses ..................................................................................................... 83 
10.4.1 General Approach ................................................................................................... 83 
10.4.2 Analysis of the Primary Efficacy Endpoints ........................................................... 83 
10.4.3 Analysis of the Secondary Efficacy Endpoints ....................................................... 83 
10.4.4 Safety Analyses ....................................................................................................... 83 
10.4.5 Baseline Descriptive Statistics ................................................................................ 84 


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10.4.6 Planned Interim Analyses ....................................................................................... 84 
10.4.7 Exploratory Analyses .............................................................................................. 84 
11 COLLABORATIVE AGREEMENTS ................................................................................. 85 
 
Material Transfer Agreement (MTA) ......................................................................... 85 
12 HUMAN SUBJECTS PROTECTIONS ............................................................................... 85 
 
Rationale For Subject Selection ................................................................................. 85 
 
Participation of Children ............................................................................................ 86 
 
Participation of Subjects Unable to Give Consent ..................................................... 86 
 
Evaluation of Benefits and Risks/Discomforts ........................................................... 86 
12.4.1 Risks ........................................................................................................................ 86 
12.4.2 Risks of Exposure to Ionizing Radiation ................................................................ 87 
12.4.3 Non-Physical Risks of Genetic Research ............................................................... 88 
12.4.4 Benefits ................................................................................................................... 88 
12.4.5 Certificate of Confidentiality .................................................................................. 88 
 
Consent Process and Documentation ......................................................................... 88 
12.5.1 Request for Waiver of Consent for Screening Activities ........................................ 89 
13 PHARMACEUTICAL AND INVESTIGATIONAL DEVICE INFORMATION .............. 89 
 
Drug MVT-5873 (IND # 144112) .............................................................................. 89 
13.1.1 Source ..................................................................................................................... 89 
13.1.2 Toxicity ................................................................................................................... 89 
13.1.3 Formulation and Preparation................................................................................... 90 
13.1.4 Stability and Storage ............................................................................................... 90 
13.1.5 Administration Procedures...................................................................................... 90 
13.1.6 Incompatibilities ..................................................................................................... 90 
14 REFERENCES ..................................................................................................................... 91 
15 APPENDICES ...................................................................................................................... 94 
 
Appendix A: Performance Status Criteria .................................................................. 94 
 
Appendix B: Toxicity Tables ..................................................................................... 95 
 
Appendix C: Investigator Agreement ....................................................................... 114 
 


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LIST OF TABLES 
Table 1: Pharmacokinetic Parameters for MVT-5873 Following Single Intravenous Doses of 
10, 30, and 100 mg/kg of MVT-5873 to Cynomolgus Monkeys................................ 17 
Table 2: Pharmacokinetic Parameters for MVT-5873 Following Intravenous Administration 
of 30 mg/kg and 100 mg/kg of MVT-5873 to Cynomolgus Monkeys on Day 1 
and Day 8 .................................................................................................................... 17 
Table 3: Dose Cohorts, Cycles Administered and Patient Disposition ........................................ 29 
Table 4: Summary of MVT-5873 Dose Limiting Toxicities and Treatment Disposition ..... 30 
Table 5: All Adverse Events, All Grades, in ≥ 30% of Subjects .................................................. 31 
Table 6: All Treatment-Related Adverse Events ≥ Grade 3 ......................................................... 32 
Table 7: MVT-5873 Human Pharmacokinetics ............................................................................ 32 
Table 8: Normalization (< 37U/mL) of CA 19-9 Levels Following Adminstration of MVT-
5873............................................................................................................................. 33 
Table 9: Safety Lead-In Study Design .......................................................................................... 46 
Table 10: Safety Lead-In Cohorts ................................................................................................. 47 
Table 11: Treatment Study Design ............................................................................................... 49 
Table 12: Treatment Guidelines (If Two Different Pre-Operative MTDs by LFT Elevation 
are Determined from Safety Lead-In) ......................................................................... 49 
Table 13:Treatment Study Design (If Two Different Pre-Operative MTDs by LFT Elevation 
are Determined from Safety Lead-In) ......................................................................... 50 
 
LIST OF FIGURES 
Figure 1: Top left: pancreas, ductal adenocarcinoma, stage III .................................................... 13 
Figure 2: Tumor Growth Over Time – BxPC3 Xenograft Model with MVT-5873 Doses of 5, 
15, and 30 mg/kg as a Single Agent and in Combination with Gemcitabine/nab-
paclitaxel ..................................................................................................................... 14 
Figure 3: Immunohistochemical Staining of BxPC3 Tumor Tissue Samples at 20X 
Magnification; MVT-5873 (top panel) and Human IgG (bottom panel) .................... 15 
Figure 4: Mean MVT-5873 Serum Concentrations Over Time in BxPC3 Tumor-Bearing 
Mice and Nontumor-Bearing Mice ............................................................................. 16 
Figure 5: MVT-5873 Serum Concentration and BxPC3 Tumor Volume Versus Time ............... 16 
Figure 6: Serum Levels (AUC0-168 and Cmax) of MVT-5873 after Repeated Intravenous 
Dosing in Cynomolgus Monkeys (Males and Females Combined) on Day 1 and 
Day 8 ........................................................................................................................... 18 
Figure 7: Liver Function Test with 3mg/kg Weekly Dosing of MVT-5873 from Six Subjects ... 28 
Figure 8: Efficacy for MVT-5873................................................................................................. 34 


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Figure 9: Percent Change in Target Lesions in Cohort B3 (0.125 mg/kg MVT-5873) ................ 35 
Figure 10: The SMART System Consisting of SMART Platform ............................................... 38 
Figure 11: Ex Vivo Normal and Tumor Preservation in the SMART System ............................. 39 
Figure 12: SMART Platforms are Valuable Tools for Drug Evaluations Such as 
Pembrolizumab ........................................................................................................... 40 
Figure 13: Operating Room Workflow ......................................................................................... 58 
Figure 14: Pathologic Evaluation of Tumor and Liver Tissue Removed at the Time of 
Surgery ........................................................................................................................ 59 
Figure 15: Scientific Endpoints. Evaluation of Circulating Tumor Cells (top) and Ex Vivo 
Tissue Modeling (bottom)........................................................................................... 63 


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1 
INTRODUCTION 
 
STUDY OBJECTIVES 
1.1.1 Primary Objectives 
• Document the safety of perioperative MVT-5873 in patients undergoing pancreas and liver 
resections. 
• Determine if perioperative MVT-5873 can decrease 1-year recurrence rates for subjects 
with operable CA 19-9 producing cancers. 
1.1.2 Secondary Objective 
• Define disease free survival (DFS) for subjects treated with preoperative MVT-5873.   
1.1.3 Exploratory Objectives 
• Define overall survival (OS) for subjects treated with preoperative MVT-5873. 
• Determine the mechanism(s) of liver function test abnormalities associated with MVT-
5873 administration. 
• Determine the tumor penetration of MVT-5873 in primary tumors of the pancreas and bile 
ducts, and in metastatic colorectal cancers to the liver.   
• Evaluate the impact of MVT-5873 therapy on circulating tumor cells. 
• Develop ex vivo models for pancreatic cancer, cholangiocarcinoma, and metastatic 
colorectal cancer. 
• Evaluate chemotherapeutic and immunotherapeutic agent effects in tumors from patients 
undergoing pancreas and liver resections after pre-operative MVT-5873 therapy using a 
novel ex vivo platform, the SMART System. 
 
BACKGROUND AND RATIONALE 
1.2.1 HPB Cancers 
Cancers of the pancreas, liver (primary and metastatic) and bile ducts represent some of the most 
recalcitrant diseases encountered by the practicing oncologist. When identified early, these cancers 
can be removed with technically challenging operations. Fortunately, experience has decreased the 
perioperative complications associated with these operations. However, the ability to prevent 
disease recurrence following the procedure has not yet come to fruition. Although resection 
remains the only hope for cure, this end-point is achieved by very few. Analysis of randomized 
prospective trial data and single institution series strongly suggests that nearly half of all patients 
undergoing resections for pancreatic cancer, cholangiocarcinoma and metastatic colorectal cancer 
to the liver will experience a recurrence of disease in the first 12-15 months following removal of 
tumor(s).[1-3] In other words, these patients underwent an operation for likely abbreviated benefit 
in terms of survival. The recently reported, not yet published, data on the BILCAP 
(cholangiocarcinoma) is very similar to these outcomes below. It has been postulated for some 
time that the operation itself may hasten demise for some patients by inciting an inflammatory 
milieu and triggering an angiogenic switch in remote dormant tumor cells. Substantial data exist 


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in mice[4] supporting this concept but data in humans is admittedly lacking. We do however know 
that surgery is associated with increases in circulating tumor cell numbers, likely secondary to 
manipulation during the procedure.[5] It would be ideal to give a perioperative agent with efficacy 
against the tumor cells at the time of resection. Unfortunately, chemotherapy has deleterious 
effects on wound healing that would make resection an extremely-risky endeavor. However, a 
well-tolerated monoclonal antibody targeting a tumor cell epitope may hold promise in mitigating 
those early recurrences and thereby increasing the efficacy of resection for cancers of the pancreas, 
liver and bile ducts. This concept of immediate perioperative therapy is unique and additive to 
what is generally undertaken with high-risk cancers. For example, patients could receive standard 
neo-adjuvant and/or adjuvant therapies in addition to immediate perioperative therapy without 
altering the standard regimens. Moreover, antibody penetration and binding to tumor cells would 
be directly assessed on resected specimens, as would the effects on circulating tumor cell 
populations (which have been demonstrated to be prognostic[6-8]), which could be used to stratify 
patients for combination antibody/chemotherapy should disease recur. In short, the employment 
of immediate perioperative therapy, if demonstrated to be safe, could add an additional tool in the 
oncologist’s armamentarium for resectable high-risk cancers.  
1.2.2 Sialyl Lewis A Antigen - CA19-9 
The Sialyl Lewis A (sLea) antigen is an epitope present on Carbohydrate Antigen 19-9 (CA 19-9), 
defined by the mouse monoclonal antibody 116-NS-19-9, shown to be overexpressed on epithelial 
cell tumors.[9, 10] SLea is an oligosaccharide expressed primarily as a proteoglycan that is secreted 
and circulates as a mucin form, and also as a less well studied glycolipid form.[10, 11] The sLea 
antigen is predominantly expressed on cancer cells.[12] As a ligand for E selectin, sLea facilitates 
tumor adhesion and extravasation, key events for tumor metastasis, and is thus a marker of an 
aggressive tumor phenotype.[13] Glycolipids, such as sLea, are established targets for cancer 
immunotherapies.[14] The monoclonal antibody MVT-5873 (also referred to as HuMab-5B1 or 
5B1), the investigational agent in this study, specifically targets the sLea antigen.  
CA 19-9 is widely expressed on tumors of the gastrointestinal tract, with up to 94% of pancreatic 
cancers positive for CA 19-9 expression and high expression rates also seen in bile duct carcinomas 
and transitional cell carcinomas.[15, 16] Additionally, expression of CA 19-9 is frequently seen in 
ovarian, colon, stomach, and distal esophagus/stomach cancers. Circulating serum levels of CA 
19-9 have been validated as a biomarker for assessing the metastatic potential of pancreatic ductal 
adenocarcinomas (PDAC)[17, 18] and have been used to evaluate the aggressiveness of other 
epithelial cell cancers.[19, 20] As a known ligand for endothelial leukocyte adhesion molecules, 
CA 19-9 expression is associated with increased metastatic potential in colon cancer[13, 21, 22] 
and pancreatic adenocarcinoma.[23]  
Serum CA 19-9 levels have also been found to be informative with respect to prognosis and 
treatment effect in patients with pancreatic cancer, with several studies correlating increasingly 
higher serum levels with poorer survival outcomes.[17, 18, 24] In a Phase I/II clinical trial of nab-
paclitaxel and gemcitabine in patients with advanced pancreatic cancer, decreases in CA 19-9 
levels correlated with tumor response, PFS, and OS.[25] In a Phase II study of 5-fluorouracil-based 
chemoradiotherapy in patients with locally advanced pancreatic cancer, a greater than 90% 
reduction in CA 19-9 levels from baseline was associated with significantly improved median 
survival time, with a multivariate analysis finding a-post therapy CA 19-9 level of less than 85.5 
U/mL to be an independent prognostic factor for survival.[26]  


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On normal cells, expression of CA 19-9 is restricted to the apical brush border, a relatively 
inaccessible location due to the basement membrane and the tight junctions of mature and 
polarized ductal epithelium.[27] In patients with CA 19-9 positive tumors, about 5% are negative 
for circulating levels of CA 19-9, and this appears to be related to poor secretion or release of CA 
19-9 into the blood stream, not necessarily to expression of the CA 19-9 antigen by the tumor 
cell.[28-30] Because CA 19-9 has a high expression rate in patients with pancreatic cancer, this 
antigen was identified as a target for antibody-based biopharmaceuticals, and specifically this 
investigation of MVT-5873 in patients with PDAC. 
1.2.3 MVT-5873 
MVT-5873 (HuMab-5B1) is a fully human IgG1 lambda antibody discovered by MabVax in 
collaboration with investigators at Memorial Sloan Kettering Cancer Center (MSKCC). MVT-
5873 was identified from blood lymphocytes from a breast cancer patient following immunization 
with a sLea-KLH vaccine.[31] This vaccine has been shown to induce high titers of both IgG and 
IgM antibodies against sLea in mice and humans without cross-reactivity to other similar blood 
group carbohydrate antigens.[31] Two human monoclonal antibodies (5B1 and 7E3) with high-
affinity for sLea were identified, subsequently expressed as a recombinant antibodies, and further 
characterized.[32]  
Evaluation of the specificity of MVT-5873 demonstrated cell surface binding in sLea positive 
colon cancer (HT29 and Colo205), ovarian cancer (SW626), small cell lung cancer (DMS79), and 
pancreatic cancer (BxPC3) cell lines, but not to a sLea negative melanoma (SK-MEL28) cell 
line.[32] Importantly, MVT-5873 did not bind to Lea, sLex, Ley, or other related carbohydrates 
when evaluated by enzyme-linked immunosorbent assay (ELISA) and surface plasmon 
resonance.[32] In addition, an independent binding analysis conducted by the Consortium on 
Functional Glycomics Core H group using a glycan array with 465 distinct carbohydrates revealed 
that MVT-5873 had exquisite specificity for the carbohydrate epitope of the sLea antigen.  
MVT-5873 has been shown to be potent in complement-dependent cytotoxicity (CDC) assays and 
antibody-dependent cell mediated cytotoxicity (ADCC) assays (see below). Both of these 
mechanisms are consistent with antitumor activity. Based on these findings, MVT-5873 was 
selected for further development as a potential therapy for patients with CA 19-9 expressing tumor 
types. 
1.2.4 Preclinical Studies 
1.2.4.1 Tissue Specificity 
MVT-5873 binding to tumor TMA appeared to be specific, differentially expressed, and restricted, 
with most normal tissues lacking reactivity. Expression of sLea was present on several 
adenocarcinomas, including pancreatic cancers, a finding consistent with literature reports of sLea 
expression identified by CA 19-9 antibody binding (Figure 1). Most of the human specimens 
evaluated in the TMA analysis were negative for staining. However, expression of sLea antigen 
was found on mucous glands of the small intestine, colon (goblet cells), and rectum. There was 
also expression in exocrine pancreas, germinal center of lymph node, gallbladder, breast (ductal 
cells), and uterine cervix of normal human tissue. The observed binding pattern is consistent with 
expression in tissues producing exocrine secretions, i.e. mucins that carry the sLea antigen.  


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Strong positive staining was seen in 23/34 colon adenocarcinomas (68%), 34/58 adenocarcinoma 
metastases to the ovary (59%), and 7/9 pancreatic ductal cancers (62%) at various stages. As shown 
in the figure below, typical reactivity shows as diffuse cytoplasmic staining, with some tumor cells 
clearly showing distinct staining at the cell membrane level. In addition, signet ring-metastatic to 
ovaries, some lung (i.e. bronchioalveolar, mucoepidermoid) and metastatic breast cancer lymph 
node biopsy cores were found to be strongly positive, albeit at lower frequencies. In contrast, only 
2/43 prostate cancer samples (5%) and 0/51 gastrointestinal stromal tumors (GIST) specimens 
were positive (data not shown). 
 
Figure 1: Top left: pancreas, ductal adenocarcinoma, stage III 
Top center: sigmoid colon, carcinoma stage IIIB 
Top right: lung adenocarcinoma, stage IB 
Bottom left: urinary bladder, mucinous adenocarcinoma, stage IV 
Bottom center: ovary, metastatic carcinoma from colon 
Bottom right: lymph node, breast carcinoma, stage IIIA 
 
1.2.4.2 Evaluation of MVT-5873 in Murine Xenograft Models 
In an early exploratory study, the antitumor potential of MVT-5873 was assessed using a Colo205-
luc xenograft model of metastatic colon cancer in SCID mice.[32] Across two experiments, groups 
of 5 mice were given either 4 doses of MVT-5873 at 5 mg/kg (20 mg/kg total dose) or 6 doses of 
MVT-5873 at 5 mg/kg (30 mg/kg total) intraperitoneally, each over the course of 21 days, while 
animals in the control groups received injections of phosphate buffered saline (PBS). Across all 
the control animals, the average median survival was 102 days and all died within 155 days. 
Treatment improved survival significantly; median survival in animals that received 4 doses of 
MVT-5875 was 207 days (p < 0.05; HR = 3.46), and in the animals that received 6 doses of MVT-
5873, median survival had not yet been reached at day 301, the termination of the experiment (p 
< 0.01; HR =6.375). 


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To further evaluate the antitumor activity of MVT-5873, a series of in vivo studies were conducted 
utilizing human pancreatic cancer (BxPC3) xenograft models.  
The combination of MVT-5873, both a single agent and in combination with gemcitabine and nab-
paclitaxel in mice bearing BxPC3 tumor xenografts was evaluated. In this study MVT-5873 was 
administered as doses of 5, 15, and 30 mg/kg, blood samples for PK analysis were collected from 
all study groups, and tumor tissues were harvested at the end of study for IHC staining. 
As had been observed in the previous BxPC3 xenograft experiments, single-agent MVT-5873 
demonstrated tumor growth inhibition and growth delay at all dose levels compared to controls 
(Figure 2).  
 
Figure 2: Tumor Growth Over Time – BxPC3 Xenograft Model with MVT-5873 Doses of 5, 15, and 
30 mg/kg as a Single Agent and in Combination with Gemcitabine/nab-paclitaxel 
Tumor tissue samples taken at the end of treatment were sectioned and stained for the presence of 
the sLea target using MVT-5873 as a probe Figure 3.  Human IgG using goat anti-human IgG 
antibody was used as a probe for residual MVT-5873 bound to tumor post administration. 
Representative tissue staining samples are depicted. IHC staining signal intensities, recorded as 
optical densities, across the two panels are shown in the Figure 3 below.  
In the Figure 3, top panel, staining the presence of the sLea was high and similar in all samples, 
indicating a relative abundance of the sLea target in these tissues. These data provide evidence that 
upon treatment of gemcitabine plus nab-paclitaxel there is no change in expression of the target 
epitope.  In the bottom panel, when stained with human IgG that lacks binding to the target epitope, 
the presence of residual MVT-5873 in tumor tissue was observed across all MVT-5873 treatment 
groups, with staining density correlating with response.  The complete lack of staining in the 
chemotherapy alone group serves as a negative control. 


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As shown in the Figure 3, signal intensities of IgG staining across all MVT-5873 treatment groups 
were higher than that of the human IgG control, indicating binding selectivity of MVT-5873 in 
tumor tissue. There was a significant difference in signal intensity between the MVT-5873 5 mg/kg 
+ chemotherapy group and the MVT-5873 15 mg/kg + chemotherapy group (P < 0.05), suggesting 
dose-dependent binding of MVT-5873 to tumor tissues. 
 
 
 
Figure 3: Immunohistochemical Staining of BxPC3 Tumor Tissue Samples at 20X Magnification; 
MVT-5873 (top panel) and Human IgG (bottom panel)  
These xenograft studies indicate that MVT-5873 has activity in the known sLea-bearing tumor 
models. 
Analysis of MVT-5873 binding to tumor tissue by IHC revealed an apparent dose-dependent 
uptake of MVT-5873 in tumor tissue. 
Serum concentrations were measured.  Further analysis of these data shown in Figure 4 and Figure 
5 indicate an inverse relationship between MVT-5873 serum concentrations and tumor volume. 
This suggests that the presence or expansion of the sLea target, either on tumor tissue or in 
circulation, decreases the amount of free MVT-5873 in the serum and contributes to the systemic 
clearance of MVT-5873. 
 
 


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Figure 4: Mean MVT-5873 Serum Concentrations Over Time in BxPC3 Tumor-Bearing Mice and 
Nontumor-Bearing Mice 
 
 
Figure 5: MVT-5873 Serum Concentration and BxPC3 Tumor Volume Versus Time 
These studies support the clinical evaluation of MVT-5873, as a single agent and in combination 
with chemotherapy, in subjects with pancreatic cancer and other sLea positive tumor types. 
1.2.4.3  
Pharmacokinetics 
1.2.4.4 Single-Dose Pharmacokinetics 
In a single-dose IV PK study in cynomolgus monkeys (non-GLP Study 20068188), MVT-5873 
serum levels were determined over a one-month period using an ELISA procedure. MVT-5873 
exhibited a low clearance from serum (0.384 to 0.503 mL/min/kg) and a low volume of distribution 
(40.9 to 83.0 mL/kg), with a resultant long half-life (65.2 to 217 hours) at dose levels of 10, 30 or 
100 mg/kg MVT-5873 (Table 1). 


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Table 1: Pharmacokinetic Parameters for MVT-5873 Following Single Intravenous Doses of 10, 30, 
and 100 mg/kg of MVT-5873 to Cynomolgus Monkeys  
Dose 
(mg/kg) Sex 
Tmax 
(h) 
Cmax 
(µg/mL) 
AUC0-t 
(µg∙h/mL) 
t1/2 
(h) 
CL 
(mL/min/kg) 
Vd 
(mL/kg) 
10 
 Female  
0.250 
141 
12,800 
NC 
NC 
NC 
Male 
0.250 
254 
22,900 
65.2 
0.424 
40.9 
30 
 Female  
0.280 
499 
41,900 
NC 
NC 
NC 
Male 
0.250 
736 
64,700 
217 
0.384 
120 
100 
 Female  
0.750 
1780 
169,000 
103 
0.503 
74.9 
Male 
0.750 
2190 
213,000 
126 
0.456 
83.0 
Abbreviation: NC=Not Calculated (coefficient of determination less than 0.800 or the extrapolation of the 
AUC to infinity represented more than 20% of the total area) 
The low serum clearance seen with MVT-5873 is typical of monoclonal antibodies, where the 
main route of elimination is generally thought to be by receptor binding and internalization and/or 
protein catabolism. The low volume of distribution is typical for a monoclonal antibody, since it 
is similar to the volume of plasma for the cynomolgus monkey and suggests limited distribution 
into tissue. 
1.2.4.5 Repeat-Dose Pharmacokinetics 
A multiple-dose toxicity study in cynomolgus monkeys (non-GLP Study 20068122) evaluated the 
effects of MVT-5873 (30 or 100 mg/kg) administered IV once a week for 2 weeks (2 doses). The 
toxicokinetic evaluations were conducted over each dosing interval on Days 1-7 and Days 8-15, 
revealing that exposure, measured by AUC0-168, was approximately dose-proportional and similar 
across the dosing interval for both sexes, ranging from 26,600 to 146,00 µg•hr/mL for dose levels 
of 30 and 100 mg/kg, respectively (Table 2, Figure 6). There was minor MVT-5873 plasma 
accumulation when administered once weekly. Similarly, in a GLP 4-week once weekly (4 doses) 
IV toxicity study, trough plasma levels measured weekly were either similar to or greater than 
Week 1 indicating good exposure to MVT-5873 over the 4-week dosing period. 
Table 2: Pharmacokinetic Parameters for MVT-5873 Following Intravenous Administration of 30 
mg/kg and 100 mg/kg of MVT-5873 to Cynomolgus Monkeys on Day 1 and Day 8 
Day 
Dose (mg/kg) 
Sex 
Cmax (μg/mL) 
AUC0-168 (μg•h/mL) 
1 
30 
Female 
843 
33,300 
30 
Male 
977 
34,800 
30 
Mean (M&F) 
910 
34,050 
100 
Female 
2260 
151,000 
100 
Male 
2380 
118,000 
100 
Mean (M&F) 
2320 
134,500 
8 
30 
Female 
760 
38,400 
30 
Male 
881 
48,900 
30 
Mean (M&F) 
821 
43,650 
100 
Female 
2540 
212,000 
100 
Male 
2450 
148,000 
100 
Mean (M&F) 
2495 
180,000 


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Day 
Dose (mg/kg) 
Sex 
Cmax (μg/mL) 
AUC0-168 (μg•h/mL) 
M= Male; F = Female 
 
Figure 6: Serum Levels (AUC0-168 and Cmax) of MVT-5873 after Repeated Intravenous Dosing in 
Cynomolgus Monkeys (Males and Females Combined) on Day 1 and Day 8 
In addition to assessing PK in cynomolgus monkeys, serum levels of MVT-5873 were measured 
at various times during a multiple dose PK study in both nontumor- and tumor-bearing SCID mice. 
After intraperitoneal administration, MVT-5873 serum levels were maintained at an average of 
46.1 µg/mL in nontumor-bearing mice. Mice with established CA 19-9 expressing tumor 
xenografts demonstrated lower serum levels, indicating a relatively higher clearance compared to 
nontumor-bearing mice. 
Further information on the pharmacokinetics of MVT-5873 in mice the presence and absence of 
tumor was collected as part of the second BxPC3 xenograft study described above, which 
evaluated MVT-5873 as a single agent at doses of 5, 15, and 30 mg/kg as a single agent and in 
combination with 80 mg/kg of gemcitabine plus 20 mg of nab-paclitaxel. This study included an 
additional treatment group of nontumor-bearing mice that were treated with MVT-5873  
15 mg/kg. 
Serial pre-dose (Cmin) concentrations of MVT-5873 were collected on Days 13, 16, 23, 30, and 37, 
with an additional sample collected 1 week later, on Day 44. As shown in the figure below, in the 
absence of tumor, serial Cmin MVT-5873 concentrations (15 mg/kg dose level) appeared to slightly 
accumulate throughout treatment. However, in all tumor-bearing animals, serial Cmin values 
declined over time, as had been observed previously.  
1.2.4.6 Preclinical Safety 
The preclinical studies conducted to determine the safety of MVT-5873 are summarized in the 
table below. Several toxicology studies have been conducted with MVT-5873 in cynomolgus 
monkeys and included a 4-week (4 dose) GLP safety study, a 2-week (2 dose) exploratory non-
GLP toxicology study, and a single dose tolerability study. All studies were conducted at Charles 
River Laboratories (Reno, NV). 
To support the cynomolgus monkey as an appropriate model for MVT-5873 toxicology studies, 
pivotal (GLP) tissue cross-reactivity studies were conducted to assess the binding of MVT-5873 
to cryosections (or to fixed blood) of normal human tissues (GLP Study 20067038) and normal 


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cynomolgus monkey tissues (GLP Study 20074271); these studies were conducted at Charles 
River Laboratories (Pathology Associates, Frederick, MD). 
Study 
Type 
and 
Duration 
Route 
/ 
Mode 
of 
Administration 
Species 
Doses 
Study 
No. 
Compliance 
Single dose 
Single-dose tolerability 
and pharmacokinetics 
with 4 week postdose 
observation/blood 
sampling period 
IV slow bolus (1-3 min) or 
30-min infusion via a 
saphenous vein 
Monkey/ 
Cynomolgus 
0, 10, 30 mg/kg 
(slow bolus) 
100 mg/kg (30-
min infusion) 
20068188 
Non-GLP 
Repeat-dose studies 
Once weekly (2 doses) 
toxicity 
and 
toxicokinetic 
study 
with terminal sacrifice 
2 weeks after the last 
dose 
IV slow bolus (1-3 min) or 
30-min infusion via a 
saphenous vein 
Monkey/ 
Cynomolgus 
0, 
30 mg/kg 
(slow bolus) 
100 mg/kg (30-
min infusion) 
20068122 
Non-GLP 
Once weekly (4 doses) 
toxicity 
and 
toxicokinetic 
study 
with terminal sacrifice 
1 week after the last 
dose and with a 4-week 
recovery 
IV slow bolus (1-3 min) or 
30-min infusion via a 
saphenous vein 
Monkey/ 
Cynomolgus 
10, 
30 mg/kg 
(slow bolus) 
0, 100 mg/kg 
(30-min 
infusion) 
Recovery 
(0, 
30, 100 mg/kg) 
20068123 
GLP 
Other toxicity studies 
Tissue cross-reactivity 
(40 
tissues 
from 
3 donors) 
In 
vitro 
(cyrosectioned 
tissue) 
Monkey/ 
Cynomolgus 
2 and 10 µg/mL 20067038 
GLP 
Tissue cross-reactivity 
(40 
tissues 
from 
3 donors) 
In 
vitro 
(cyrosectioned 
tissue) 
Human 
2 and 10 µg/mL 20074271 
GLP 
Blood 
compatibility 
(hemolysis 
and 
erythrocyte clumping) 
In vitro heparinized blood 
from Lewis A positive 
phenotype on red blood 
cells 
Human 
Final 
blood 
concentrations: 
57.5 
– 
384 
µg/mL  
323966 
1.2.4.7 Species Selection 
The cynomolgus monkey is considered a relevant biological species for evaluating the safety of 
MVT-5873, since this species, like humans, expresses the gene (FUT3) responsible for expression 
of the pharmacologic target sLea. In contrast, both mice and rats lack a functional FUT3 and do 
not express sLea. To establish the tissue expression of the sLea target in standard toxicology animal 
models, binding of MVT-5873 to tissue microarrays obtained from cynomolgus monkey, mouse, 
and rat was studied. As expected from the literature and from previous studies with MVT-5873 
using normal human tissue, binding of MVT-5873 to cynomolgus monkey tissue was seen in 
mucus secreting epithelium in the gastrointestinal tract, as well as in other related tissues (e.g., 
salivary glands). Unlike cynomolgus monkey tissue microarrays, the tissue microarrays from 
mouse and rat showed no specific binding for MVT-5873. These results confirm literature reports 
that rodents do not express sLea and thus are not appropriate for nonclinical safety testing, and that 


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cynomolgus monkeys do express the pharmacologic target and are appropriate for toxicity testing 
with MVT-5873.   
1.2.4.8 Repeat Dose Toxicity 
1.2.4.8.1 MVT-5873: 2-Week Once Weekly (2 Doses) Toxicity Study 
In a pilot toxicity study in cynomolgus monkeys (nonGLP Study 20068122), MVT-5873 was 
administered IV as a slow bolus dose at 0 and 30 mg/kg or as a 30-min infusion at 100 mg/kg on 
study Days 1 and 8. The vehicle was 25 mM histidine, 150 mM sucrose, 55 mM sodium chloride, 
0.02% Tween 80 at pH 6.0. Observations were recorded during the study. Samples for hematology, 
coagulation, urinalysis and clinical chemistry were collected for all animals once prestudy and on 
Day 23 or, for urinalysis, on Day 25. Animals were necropsied on Day 25, organs weighed and 
tissue collected for histopathological examination. 
Toxicokinetic samples were drawn for all animals on Days 1 and 8 at 0.25, 6, 12, 24, 72, and  
168 hours post dose. Samples were also collected on Day 23 prior to sacrifice (see Section 1.2.4.8.2 
for discussion of repeat-dose toxicokinetics). 
There was no mortality, no changes in clinical observations, no changes in food consumption, or 
adverse reactions to MVT-5873. There were no MVT-5873-related changes in hematology, serum 
chemistry, urinalysis or coagulation parameters, and no MVT-5873-related macroscopic findings 
noted at terminal necropsy. 
Non-adverse microscopic findings considered related to MVT-5873 were noted at 100 mg/kg in 
the gallbladder (minimal eosinophilic infiltration) in both the male and female monkeys and in the 
liver (mild Kupffer cell hypertrophy) in the male. Mild mononuclear cell infiltrates noted in the 
kidney of the female at 100 mg/kg was of uncertain relationship to the test article. These 
histological changes were not seen in the pivotal GLP 4-week study. 
1.2.4.8.2 MVT-5873: 4-Week Once Weekly (4 Doses) Toxicity Study 
In the pivotal GLP 4-week toxicity study in cynomolgus monkeys (GLP Study 20068123), 
MVT-5873 was administered IV as a 30-minute infusion at 0 and 100 mg/kg and as a slow bolus 
dose at 10 and 30 mg/kg on study Days 1, 8, 15 and 22. The vehicle was the same as the clinical 
formulation and consisted of 25 mM histidine, 150 mM sucrose, 55 mM sodium chloride, 0.02% 
Tween 80, pH 6.0. Observations were recorded during the study. Ophthalmic examinations were 
conducted predose and during Weeks 4 and 8. Electrocardiograms, heart rate, and waveform 
intervals (PR, QRS, RR, QT, and QTc Bazett’s) were recorded predose and during Weeks 4 and 
8. Samples for hematology, coagulation, and clinical chemistry were collected for all animals once 
predose, on Day 30, and at the end of the 4-week reversal period (Day 58). Samples for assessment 
of anti-MVT-5873 antibodies were drawn predose, on Day 29, and near the end of the 4-week 
reversal period (Day 57). Animals were necropsied, organs weighed and tissue collected for 
histopathological examination on Day 30 for the main sacrifice groups (3/sex/group) and on 
Day 58 for the reversal groups (2/sex at 0, 30 and 100 mg/kg). 
Toxicokinetic samples were drawn at various times over a one-week period following the first 
dose administration, at weekly intervals until the main sacrifice, and then again at the end of the 
4-week reversal period. 


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There was no mortality and no MVT-5873 related changes in clinical observations, body weight, 
food consumption, ophthalmic exams, or cardiac parameters. There were no MVT-5873 related 
changes in hematology, serum chemistry, or coagulation parameters and no MVT-5873 related 
macroscopic findings noted at the main necropsy or at the reversal necropsy. In contrast to the 
previous cynomolgus monkey toxicity study, no MVT-5873 related microscopic findings were 
observed in this GLP study. 
The toxicokinetics of MVT-5873 in female and male cynomolgus monkey serum demonstrated 
similar systemic exposure as in the previous toxicity study, with mean weekly trough values over 
the 4-week study period being similar to, or greater than, those observed during Week 1. Although 
MVT-5873, a fully human monoclonal antibody, generated anti-MVT-5873 antibodies in most 
animals at all dose groups, the presence of these antibodies had no apparent effect on serum levels 
of MVT-5873 and was not associated with any microscopic changes. Two monkeys tested positive 
for anti-MVT-5873 antibodies prior to treatment with MVT-5873 and also demonstrated higher 
serum clearance of MVT-5873 on Day 1 versus monkeys with no predose antibodies; these results 
indicate that the positive results prestudy were likely cross-reactive antibodies. Development of 
antibodies during the study was expected following administration of a human monoclonal 
antibody to cynomolgus monkeys. 
In summary, intravenous administration of MVT-5873 up to 100 mg/kg once weekly for 4 weeks 
generated no adverse toxicological effects. The dose of 100 mg/kg is near the maximum feasible 
dose based on maximum formulation concentration and maximum acceptable dose volume in 
monkeys. An expected immune reaction was induced in cynomolgus monkeys after treatment with 
MVT-5873, but had no apparent effect on serum levels of MVT-5873, which generally remained 
constant throughout the 4-week study period. 
1.2.4.9 Tissue Cross-Reactivity Studies 
The objective of this study was to determine the potential cross-reactivity of MVT-5873, a 
monoclonal human IgG antibody directed against Sialyl Lewis (a), with cryosections of human 
tissues. Sialyl Lewis (a) is a carbohydrate antigen present on O-glycans on the surfaces of cells 
and is often associated with high grade tumors from various tissues.[12, 33]  Sialyl Lewis (a) has 
been reported to be expressed in a number of normal tissues as well.[34-37]  
Pivotal (GLP) tissue cross-reactivity studies of MVT-5873 with cryosections (or with fixed blood) 
of normal human tissues (GLP Study 20067038) and normal cynomolgus monkey tissues (Study 
20074271) were conducted using 41 different tissue types from typically 3 donors/tissue. In 
addition, positive control (cryosections of human DMS 79 cells), negative control (cryosections of 
human Jurkat cells), and ancillary control (cryosections of human colon which was previously 
shown to cross react with MVT-5873) tissues were used to ensure integrity of the staining. As a 
further control to ensure adequacy of the tissue sample, sections were immunostained for 
β2-microglobulin, a relatively ubiquitous epitope. To ensure specificity of the MVT-5873 
antibody, all tissue sections were concurrently stained with a negative control human IgG1 kappa 
antibody. 
The optimal concentration of MVT-5873 was determined by finding the lowest concentration of 
test article that produced the maximum (plateau) binding to the target antigen (2 µg/mL). This 
concentration and a 5-fold increase (10 µg/mL), which did not incur excessive nonspecific staining 
of control samples and/or test tissues, were used for the definitive tissue cross-reactivity studies. 


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MVT-5873 produced moderate to intense membrane, cytoplasm, and cytoplasmic granule staining 
of the positive control material (cryosections of human DMS 79 cells) at both staining 
concentrations. MVT-5873 did not specifically react with the negative control material 
(cryosections of human Jurkat cells) at either staining concentration.  The control article, HuIgG1, 
did not specifically react with either the positive or negative control materials or with the any of 
the tissue slides.  There also was no staining of the assay control slides.  MVT-5873 produced 
moderate to intense staining of membrane, membrane granules, cytoplasm, and cytoplasmic 
granules in frequent mucosal epithelial cells and weak to strong staining of occasional extracellular 
material with morphology and location expected for mucus in the ancillary control material 
(cryosections of human colon) at both staining concentrations.  There was no staining of any 
human colon tissue elements from the ancillary control material with either concentration of 
HuIgG1 or in the respective assay control slide.  The excellent specific reactions of MVT-5873with 
the positive control material and the lack of specific reactivity with the negative control material, 
as well as the lack of reactivity of the control article, indicated that the assay was sensitive, specific, 
and reproducible. 
The results of human tissue staining with MVT-5873 at 10 and 2 µg/mL and with the control 
article, HuIgG1, at 10 and 2 µg/mL are presented in GLP Study 20067038 and summarized below. 
Epithelium 
MVT-5873 variably stained membrane, membrane granules, cytoplasm, and/or cytoplasmic 
granules in epithelium in a variety of human tissues including bladder (transitional), breast, colon 
(mucosa), eye (conjunctiva), Fallopian tube (mucosa), gallbladder (mucosa), esophagus 
(squamous, submucosal glands), small intestine (mucosa), stomach (mucosa), kidney (tubular), 
liver (bile duct), lung (bronchial, bronchiolar), ovary (surface, follicle), pancreas (acinar, ductal), 
pituitary (adenohypophysis), prostate (glandular, ductal), rectum (mucosa), salivary gland (acinar, 
ductal), skin (sweat gland, hair follicle, epidermis), testis (seminiferous tubules), thymus, tonsil 
(squamous, surface, crypt), ureter (transitional), cervix (external ostium [squamous], internal 
ostium, endocervical glands), and uterus (endometrium, surface, glandular).  This staining was 
equivalent, reduced in intensity and/or frequency, or absent at the lower staining concentration.  
Sialyl Lewis (a) background expression has been reported in a variety of tissues including 
pancreas, gallbladder, stomach, colon, bronchial tree, endometrium, salivary glands, kidney and 
prostate.  Based on the wide range of Sialyl Lewis (a) background expression, the observed 
staining of epithelium in the human tissues was judged expected.[34-37] 
Mononuclear cells 
MVT-5873 weakly to moderately stained cytoplasm and cytoplasmic granules in rare to occasional 
resident, migrating, and/or infiltrating mononuclear cells in lymph node at the higher staining 
concentration.  This staining was reduced in frequency to rare at the lower staining concentration.  
No literature was available describing Sialyl Lewis (a) expression by mononuclear cells; thus, the 
observed staining of this cell type was judged unexpected. 
Extracellular material 
MVT-5873 variably stained extracellular material in a number of tissues including bladder, colon, 
eye, Fallopian tube, gall bladder, esophagus, small intestine, stomach, kidney, lung, ovary, 
pancreas, pituitary, placenta, prostate, rectum, salivary gland, testis, thymus, thyroid, tonsil, ureter, 
cervix, and uterus.  This staining was generally equivalent at both staining concentrations.  MVT-


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5873 stained extracellular material generally had morphology and location consistent with that 
expected for mucus, serum components, colloid, lens protein, and/or serum components. Sialyl 
Lewisa is reported to be secreted into the serum in the form of high-molecular mucin-like 
glycoproteins; thus, the observed staining of extracellular material was judged expected.[12, 33]   
Mesothelium 
In one testis sample, MVT-5873 weakly to moderately stained the cytoplasm of occasional 
mesothelial cells at both staining concentrations.  No literature was available describing Sialyl 
Lewis (a) expression by mesothelium; thus, the observed staining of this cell type was judged 
unexpected. 
Summary 
Consistent with the literature for expression of sLea, MVT-5873 stained a variety of epithelial cell 
types and related extracellular mucus-like material in both human and cynomolgus monkey tissues, 
all consistent with epithelial cell secretions.  The structures stained included mucosal/secretory 
epithelium of the bladder, breast, eye (conjunctiva), Fallopian tube, gastrointestinal tract, kidney 
tubules, liver (bile duct), lung (bronchial, bronchiolar) ovary, pancreas (acinar ducts), pituitary 
(adenohypophysis), prostate (ducts), salivary gland (ducts), skin (sweat gland, hair follicle, 
epidermis), testis (seminiferous tubules), thymus, tonsils, ureter, cervix, and uterus. These 
epithelial cells were similarly stained in both human and cynomolgus monkey tissues, except for 
the ovary and testes, which were only stained in human tissue; however, extracellular mucus 
material in cynomolgus monkey testes did stain positive. 
Additional staining was seen intracellularly in lymph node of one human and one cynomolgus 
monkey donor tissue and in the mesothelium of one human teste.  Staining of these tissues is 
considered to be of little-to-no toxicologic relevance as the cytoplasmic compartment is generally 
thought to be inaccessible to monoclonal antibodies when administered intravenously to animals.  
The lack of toxicological significance of the epithelial secretory cell staining is supported by the 
lack of toxicology findings at doses up to 100 mg/kg/week in the GLP 4-week MVT-5873 
toxicology study in cynomolgus monkeys. 
1.2.5 Effects in Humans 
MVT-5873 is currently being evaluated in a Phase I/II study both as a single agent and in 
combination with gemcitabine/nab-paclitaxel. Trial MV-0715-CP-001.01 is a Phase 1 Safety and 
Tolerability Study of Human Monoclonal Antibody 5B1 (MVT-5873) as Monotherapy and with 
Chemotherapy in Subjects with Pancreatic Cancer or Other CA 19-9 Positive Malignancies. The 
primary objective for this trail is to determine the safety and maximum tolerated dose of MVT-
5873 administered as monotherapy, determine safety and maximum tolerated dose of MVT-5873 
administered in combination with nab-paclitaxel plus gemcitabine and to determine the 
pharmacokinetics of MVT-5873.  Secondary objectives are to evaluate tumor response rate (based 
on RECIST 1.1) to MVT-5873 and evaluate the duration of response This study is currently 
ongoing in the dose escalation phase for both the monotherapy arm and the combination 
chemotherapy arm is being evaluated in an expansion cohort at an MVT-5873 dose of 0.125 
mg/kg.  
Trial MV-0715-CP-001.01 enrolled the first subject on 17-Feb 2016 and as of 15-Dec 2017 had 
accrued 32 subjects with pancreatic adenocarcinoma or other CA 19-9 positive malignancies in 


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24 
 
the single agent study as summarized below.   The population of this study consists of adults (males 
and females), 18 years of age and older who have locally advanced or metastatic pancreatic ductal 
adenocarcinoma or other CA 19-9 positive malignancies. 
Demographics/Baseline Characteristics 
Single Agent Subjects 
Male : Female 
16 : 16 
Median age, (range), years 
65 (51-87) 
ECOG PS 0 : 1, n (%) 
7(22) : 25(78) 
Prior Therapy: 
 No. of systemic therapies 
    1 
    2 
    3 
    4+ 
Radiation 
Surgery  
  Primary tumor 
  Metastatic disease 
  
  
8 
5 
11 
8 
9 
17 
16 
2 
Primary Disease Site (n) 
  Pancreas 
Colon/rectum 
Other (unknown primary) 
  
29 
1 
2 
Stage at entry (n) 
  III 
  IV 
  
2 
30 
 
MVT-5873 was administered on an every-other-week schedule (Q2W) (Cohorts A1 and A2) and 
then modified to a weekly schedule (QW) based dose limiting toxicity at 3 mg/kg and on initial 
PK data. The QW dose escalation schema is shown below and further summarized in the 
subsequent table. 
 


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Parameter 
Cohort Identifier 
A1 
A2 
A4 
A5 
A6 
A7 
Number of subjects 
6 
3 
4 
3 
6 
4 
Dose (mg/kg) 
1 
3 
1 
2 
3 
2.5 
Schedule 
Q2W 
Q2W 
QW 
QW 
QW 
QW 
Dose 
intensity 
(weekly 
mg/kg 
equivalent) 
0.5 
1.5 
1 
2 
3 
2.5 
1.2.5.1 Summary of Safety Information 
As of December 15, 2017, the single agent MTD for every other week (Q2W) and weekly (QW) 
schedules were defined as 1 mg/kg with dose limiting liver toxicity observed at 3 mg/kg for Q2W 
and 2 mg/kg for QW. The single agent weekly schedule has explored MVT-5873 doses ranging 
from 1 to 3.0 mg/kg (1.0, 2.0, 2.5 and 3.0 mg/kg). Based on the occurrence of dose limiting liver 
toxicity characterized by increased transaminases (AST/ALT) and blood bilirubin (Grade 3 and 
single Grade 4), MVT-5873 doses ≥ 2.0 mg/kg were considered to have exceeded the maximum 
tolerated dose (MTD).  
The MTD for single agent MVT-5873 was determined to be 1 mg/kg. However, based on clinical 
data single-agent MVT-5873 at a dose of 3 mg/kg appears to demonstrate dose limiting toxicity 
with increases in liver transaminases and blood bilirubin. When seen, these abnormalities occurred 
within a few days of drug administration, were self-limited and resolved spontaneously within 
eight days and resulted in no permanent liver abnormalities. Moreover, dosing >1.0 mg/kg 
appeared 
to 
be 
a 
more 
effective 
dose 
in 
terms 
of 
RECIST 
responses 
than  
1.0 mg/kg, and subjects on doses >1.0 mg/kg received more doses before PD was documented. A 
secondary aim of Trial MV-0715-CP-001.01 was to determine the mechanism(s) of this DLT, 
which may be related to Kupffer cell activation and not necessarily any direct injury related to the 
antibody. Non-human primate data support this hypothesis.  


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Patient #1 
 
Patient #2 
 


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Patient #3 
 
Patient #4 
 
 
Patient #5 
 


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28 
 
Patient #6 
 
Figure 7: Liver Function Test with 3mg/kg Weekly Dosing of MVT-5873 from Six Subjects 
As a single agent, severe (Grade 3+) toxicities considered related to MVT-5873 have 
predominately included reversible liver function abnormalities (manifest as increased 
transaminases and blood bilirubin), and infusion reactions. Infusion reactions decreased in 
frequency and severity following initiation of a prophylactic regimen (slower infusion rate and IV 
steroids). Low-grade (Grades 1 and 2) treatment-related toxicities consist predominately of 
toxicities related to immune activation (chills, fever, malaise, pruritus, rash, and skin induration). 
No significant related hematologic toxicity has been observed. 
To date, no significant EKG changes (e.g., increases in QTcF) have been observed. 
In summary, the predominate toxicity of MVT-5873 as a single agent and/or in combination with 
gemcitabine/nab-paclitaxel is dose limiting liver function test abnormalities. Increases in liver 
function tests are generally seen early (Day 3) and are reversible. Infusion reactions, when seen, 
generally appear during the infusion or shortly thereafter and appear less likely with slower 
infusion rates or with the use of steroid premedication. 


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A summary of the safety profile and adverse events are summarized below. 
Table 3: Dose Cohorts, Cycles Administered and Patient Disposition 
 
Cohort 
 
 
 
 
Baseline CA19-9 (U/mL) 
Patient Disposition 
< 2500 
≥ 2500 
On 
Study 
Off Study 
n 
Median 
Cycles 
(range) 
n 
Median 
Cycles 
(range) 
Toxicity 
PD 
Other 
A1 
1 
4 
5 
1.25 (1-3) 
0 
0 
5 
1 
A2 
2 
4.5 (4-5) 
1 
7.5 
0 
0 
2 
1 
A4 
4 
5.625 (1.5-13.5) 
2 
2 (1.25-2.75) 
0 
0 
5 
1 
A5 
5 
2 (1.5-6.25) 
1 
2 
0 
0 
6 
0 
A6 
0 
- 
6 
1.375 (1-2) 
0 
0 
6 
0 
A7 
4 
4.375 (0.25-10.75) 1 
1 
1 
1 
3 
0 
Total 
16 
4 (0.25-10.75) 
16 
1.375 (1-7.5) 
1 
1 
27 
3 
B3 
2 
0.875 (0.75 – 1.0) 
1 
1 
0 
0 
1 
2 
B0 
3 
2.0 (0.5-6.75) 
1 
3.5 
2 
0 
1 
1 
Total 
5 
1 (0.5-6.75) 
2 
2.25 (1-3.5) 
2 
0 
2 
3 


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Table 4: Summary of MVT-5873 Dose Limiting Toxicities and Treatment Disposition 
Cohort (n) 
Individual Patient Events (Cycle 1) 
Treatment Disposition 
 
Day Toxicity 
CTCAE 
Grade 
Duration 
(days) 
Adjustment 
Total 
Cycles 
A1 (6) 
None 
A2 (3) 
3 
↑ Bilirubin 
3 
12 
↓ dose 
4 
3 
↑ ALT 
3 
2 
↓ dose 
5 
A4 (6) 
None 
A5 (6) 
8 
↑ Bilirubin 
3 
7 
↓ dose 
1.5 
3 
↑ ALT,↑ AST 
3, 3 
3,3 
↓ dose 
1.25* 
A6 (6) 
5 
↑ ALT,↑ AST 
3, 3 
3, 3 
↓ dose (x2) 
1.25 
3 
↑ AST 
3 
6 
↓ dose 
1.5 
A7 (5) 
3 
↑ ALT,↑ AST 
3, 3 
5,5 
d/c 
0.25# 
29 
↑ ALT,↑ AST 
3, 3 
2,2 
↓ dose 
3.25* 
3 
↑ ALT,↑ AST 
3, 4 
3,5 
↓ dose 
3* 
B3 (3) 
8 
↑ ALT 
3 
7 
delay 
0.75 
3 
↑ Bilirubin 
3 
5 
delay 
1 
*Continued on treatment; #discontinued (d/c) after 1st dose, resolution to Grade 2 by Day 5 
 
The adverse event experience for MVT-5873 as a single agent is listed in the Appendix B and 
summarized below in the accompanying Table 5 and Table 6. 


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Table 5: All Adverse Events, All Grades, in ≥ 30% of Subjects 
Preferred Term 
n (%) 
Cohort At MTD Cohort Exceeds MTD 
A1 
(n = 6) 
A4 
(n = 6) 
A2 
(n = 3) 
A5 
(n = 6) 
A6 
(n = 6) 
A7 
(n = 5) 
↑ AST 
23 (72) 
- 
2 
- 
5 
5 
11 
↑ ALT 
18 (56) 
- 
1 
1 
4 
2 
10 
↑ Alkaline phosphatase 
22 (69) 
4 
4 
- 
2 
4 
8 
↑ Bilirubin 
20 (63) 
3 
1 
- 
9 
1 
6 
Fatigue 
19 (59) 
4 
4 
1 
1 
5 
4 
Nausea 
13 (41) 
3 
1 
2 
5 
- 
2 
Hypoalbuminemia 
12 (38) 
1 
2 
- 
- 
1 
8 
Hyperglycemia 
10 (31) 
4 
2 
- 
2 
- 
2 
Vomiting 
10 (31) 
4 
1 
3 
1 
1 
- 
Back Pain 
10 (31) 
1 
- 
1 
2 
6 
- 
Anemia 
10 (31) 
1 
2 
- 
- 
- 
7 
Pneumonitis 
- 
- 
- 
- 
- 
- 
- 
Total* (n = 32) 
 
 
 


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Table 6: All Treatment-Related Adverse Events ≥ Grade 3  
Preferred Term 
n (%) 
Cohort At MTD 
Cohort Exceeds MTD 
A1 
(n = 6) 
A4 
(n = 6) 
A2 
(n = 3) 
A5 
(n = 6) 
A6 
(n = 6) 
A7 
(n = 5) 
↑ ALT 
9 (30) 
- 
- 
1 
2 
1 
5 
↑ AST 
8 (27) 
- 
- 
- 
2 
2 
4 
↑ Alkaline phosphatase 
5 (17) 
- 
1 
- 
1 
- 
3 
↑ Bilirubin 
4 (13) 
1 
- 
- 
3 
- 
- 
Pneumonitis 
- 
- 
- 
- 
- 
- 
- 
↓ Lymphocyte count 
2 (7) 
- 
- 
- 
1 
- 
1 
↑ Lipase 
1 (3) 
- 
- 
- 
1 
- 
- 
Hyperbilirubinemia 
1 (3) 
- 
- 
1 
- 
- 
- 
Infusion reaction 
1 (3) 
1 
- 
- 
- 
- 
- 
*Total adverse events recorded in all subjects across all cycles; #data as of 08/30/2017 
1.2.6 Pharmacokinetics 
MVT-5873 displays a half-life of 117.6 ± 33.4 h, clearance of 279.6 ± 313.0 mL/h, and volume of 
distribution at steady-state of 17.7 ± 21.0 L. These data demonstrate that MVT-5873 displays 
properties that are in the typical range for monoclonal antibodies. These initial PK values for the 
two different schedules of administration using a two-compartment model are summarized in the 
Table 7.  
Table 7: MVT-5873 Human Pharmacokinetics 
Regimen 
Subject 
Initial t1/2 
(h) 
Terminal t1/2 
(h) 
AUC0-∞ 
(ng•h/mL) 
Vss (mL) 
Cl (ml/h) 
Q2W  
Mean 
20.8 
193.0 
2339353 
17147 
226.3 
SD 
9.5 
93.4 
3256439 
27582 
290.1 
QW  
Mean 
37.3 
833.1 
2812486 
14922 
65.1 
SD 
14.1 
1164.4 
3247729 
12999 
68.9 
1.2.7 Reductions in Serum CA19-9 Levels 
In study MV-0715-CP-001.01, serum CA 19-9 levels are assessed both pre- and post-MVT-5873 
administration. Data on serum CA 19-9 levels indicate that serum CA 19-9 levels are uniformly 
reduced in all subjects regardless of dose. However, the probability of a CA 19-9 level within 


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normal limits (i.e., < 37 U/mL) post MVT-5873 appears to be related to dose. As shown in the 
table below, at a dose of 1 mg/kg, MVT-5873 appears to normalize an elevated CA 19-9 level in 
about 50% of subjects on Cycle 1 Day 1 and in about 20% of subjects across all administration 
days. In contrast, doses of 2 mg/kg or higher normalize CA 19-9 levels in essentially all subjects.  
Table 8: Normalization (< 37U/mL) of CA 19-9 Levels Following Adminstration of MVT-5873 
Dose 
MVT-5873 
(mg/kg) 
# 
Normal 
Post C1D1 * 
Percent 
# 
Normal 
Post All Days** 
Percent 
1 
3/6 
50% 
4/20 
20% 
2 
3/3 
100% 
10/10 
100% 
3 
1/1 
100% 
12/13 
92% 
TOTAL 
7/10 
70% 
26/43 
60% 
*Number of subjects with CA 19-9 level > 37U/mL pre MVT-5873 that was reduced to < 37U/mL 
post MVT-5873 on Cycle 1 Day 1 only. 
**Number of subjects with CA 19-9 level > 37U/mL pre MVT-5873 that was reduced to < 
37U/mL post MVT-5873 for all administration days. 
1.2.8 Responses to Therapy 
Upon review of the single agent dosing cohorts, dosing > 1 mg/kg appears to be a more effective 
dose based on RECIST responses than 1 mg/kg. Moreover, subjects on doses > 1 mg/kg remained 
on therapy longer before PD was documented indicating longer duration of response. Most 
importantly however the data clearly indicate efficacy for MVT-5873 when given as a single agent, 
and the subjects that experienced the most efficacy were those with CA 19-9 values less than 2,500 
U/ml (Figure 8). 


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Figure 8: Efficacy for MVT-5873 
The preliminary response data for MVT-5873 in combination with a standard of care 
chemotherapy are promising with 5 PR and 1 SD as best response. Figure 9 illustrates the percent 
change in target lesion for the first six subjects at a dose of 0.125 mg/kg (Cohort B3). 


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Baseline CA19-9  
▌ < 2500 U/mL 
▌ ≥ 2500 U/mL 
Figure 9: Percent Change in Target Lesions in Cohort B3 (0.125 mg/kg MVT-5873) 
1.2.9 Rationale 
In this study we are planning to give subjects a pre-operative, one-time infusion of 1 mg/kg of 
MVT-5873 at Day -3 before surgery, perform the resection and continue treatment with MVT-
5873 at the dose of 1 mg/kg.  We believe that peri-operative use of MVT-5873 adds “systemic” 
treatment during a time when none is given, despite the fact that the resection is associated with 
large increases in circulating tumors cells, and an inflammatory milieu believed to be, at least in 
part, responsible for the early recurrences observed in a substantial number of subjects. We believe 
peri-operative MVT-5873 will decrease early recurrence rates and increase DFS for subjects with 
CA 19-9 producing cancers included in this study.  
To assess safety of the combination of treatment with MVT-5873 and surgery, we are planning to 
start with enrollment into safety lead-in cohorts and carefully monitor status of the subjects during 
10 days after initial treatment and surgery.  We will continue enrollment into the study only if 
treatment in the safety lead-in cohorts are proven to be safe.  
If safety is documented with the safety-lead in cohorts at 1 mg/kg, we will dose escalate the 
single pre-operative dose of MVT-5873 to 3 mg/kg.   We want to explore this higher dose for 
pre-operative treatment because we consider the drug to be more effective at this dose, and we 


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believe the days following the operation are the most critical time to for the reasons outlined 
above. We do not believe there will be undo risk as subjects will receive the 3 mg/kg dose once.  
1.2.10 Metastasis Assays Using Ex Vivo Perfusion of Omentum  
A major goal of Dr. Hernandez’s lab is to understand how tumor cells adapt to and co-opt the liver 
microenvironment for eventual metastatic outgrowth. With tumor cells labelled and observable 
throughout week-long time courses, many downstream applications will be possible, including 
(but not limited to) interrogation of the tumor cells at various time-points and at various stages of 
the metastatic cascade, with and without forced over-expression of various genes of interest. In 
order to accomplish this, cholangiocarcinoma and pancreatic cancer tissue removed during 
pancreatic resections will be submitted to Dr. Hernandez’s laboratory. Tumor cells will be 
immediately dissociated into single cells using the Miltenyi Tumor Dissociator and labelled using 
fluorescent protein tags (Cell tracking Dyes). Labelled single tumor cells will then be injected back 
into the perfusate to simulate the metastatic process. The cells will be tracked using specialized 
camera/detector system in combination with our multi-photon microscope. 
1.2.11 Ex Vivo Hepatic Perfusion Model  
This study is an important step toward our goal of implementing an ideal tumor model system. 
The ability to recapitulate the complexities of solid human tumors for the purposes of drug 
development and testing has been, and remains, a major obstacle in the progress of cancer care. 
Despite great efforts expended on pre-clinical optimization using existing validation models, most 
drugs simply fail to demonstrate efficacy when subjected to Phase III clinical trial scrutiny.  
Our interpretation is that the currently available model systems lack the appropriate clinical 
predictive power. The reasons for the inadequacies of these model systems, which are largely based 
upon cell lines, mouse models or patient-derived xenografts, are myriad but are almost certainly 
related to the absence of the human stromal component and its intricate relationship with tumor 
cells. Indeed, modeling the multi-faceted interactions between human cancer cells and the 
multitude of various stromal components, including activated fibroblasts, immune cell infiltrate 
and the abnormal vasculature is, at present, an impossibility. The advent of a model system capable 
of accurately reproducing human tumors ex vivo carries broad implications across many fields of 
investigational medicine and brings with it the potential to fundamentally alter the translational 
research landscape. Moreover, if it were possible to represent a given patient’s tumor in that model 
system, the benefits of personalized medicine could leap from generating lists of potentially useful 
drugs to designation of efficacious agents. 
We intend to satisfy all the requirements of an ideal tumor model system by utilizing resected 
segments of tumor-containing liver and repurposing the Liver-Assist perfusion device for 
prolonged ex vivo animation via native blood vessel perfusion. This is entirely novel and has not 
been attempted elsewhere in the world. Moreover, the expertise required to accomplish this make 
it unlikely to be successful anywhere other than the clinical center. This study expands our CRC 
patient population and importantly expands it to include subjects with intrahepatic 
cholangiocarcinoma. 
We will start the model with optimization of perfusion conditions for maintenance of both tumor 
and normal liver with serial evaluation to include the following:  
1) Ultrasonographic evaluation to document preservation of tumor echogenic properties.  


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2) Core needle biopsy to document histopathologic preservation of the microscopic 
architecture and cellular viability. Sufficient tissue will be obtained for any necessary 
staining.  
3) Transcriptomic profiling will be undertaken using snap-frozen biopsies. Samples from 
a given tumor will be run together to minimize variability. Standard HiSeq RNA platform 
with a read depth of 30-40 million will be employed.  
4) Metabolomic profiling will be undertaken using snap-frozen biopsies. Samples from a 
given tumor will be run together to minimize variability. 
We’ve chosen strategically to use Genomic Expression’s OneRNA platform in the present protocol 
(refer to Section 5.2.2). This technology is designated to quickly sequence 20K genes and provide 
lists of potentially usable drugs in addition to the sequencing data from tumor and normal liver. 
The platform will be of use to us as we move forward with our ex vivo tumor model, as we 
anticipate patterns will emerge among tumors such that likely drug combinations can be estimated 
for use in our ex vivo model. We will facilitate transfer of material from any pre-operative 
biopsies/tumor removal to genomic expressions for evaluation. This will allow us to utilize various 
agents predicted by OneRNA as efficacious. This model system will enable us to evaluate drug 
delivery, cell based therapies, etc. given the unlimited use of repeat biopsies. The perfusate is also 
the ideal medium for biomarker discovery, which can be related to actual changes demonstrable 
in the tumor. Although we will not be able to use efficacious drugs in the model to treat subjects, 
we believe the information will be of immediate value in guiding subjects toward subsequent trials 
should they recur. 
Finally, we will be able to conduct metastases assays using the ex vivo tumor containing liver as 
the target organ and the tumor dissociator as above (see Section 1.2.10).  
1.2.12 Simulated Metastasis Assay with Relevant Tissue (SMART) Chamber  
Dr. Hernandez’s laboratory in the Surgical Oncology Program is also developing a novel tumor 
modeling system, referred to as the Simulated Metastasis Assay with Relevant Tissue (SMART) 
Chamber. Correlative studies in proteogenomic characterization of primary and metastatic cancers 
and ex vivo tumor tissue modeling of peritoneal metastasis will be added to this study, utilizing the 
SMART Chamber.  In conjunction with ongoing laboratory work, segments of the peritoneum are 
removed from patients with peritoneal carcinomatosis at the time of operation. This peritoneal 
tissue is utilized in the SMART Chamber system to imitate conditions of metastasis within the 
abdominal cavity. This ex vivo tissue model system allows for observation of peritoneal metastasis, 
real-time cellular imaging, and manipulation of tumor-environment interactions.  
1.2.13 The SMART System 
The SMART System is an important step toward our goal of realizing personalized translational 
cancer care. The ability to recapitulate the complexities of solid human tumors for the purposes of 
drug development and testing has been, and remains, a major obstacle in the progress of cancer 
therapy. Despite great efforts expended on pre-clinical optimization using existing validation 
models, most drugs simply fail to demonstrate efficacy when subjected to Phase III clinical trial 
scrutiny. Our interpretation is that the currently available model systems lack the appropriate 
clinical predictive power. The reasons for the inadequacies of these model systems, which are 


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largely based upon cell lines, mouse models or patient-derived xenografts, are myriad but are 
almost certainly related to the absence of the human stromal component and its intricate 
relationship with tumor cells.  
There has been a sizable expansion of oncologic pharmaceuticals that have targeted and/or 
immunomodulatory effects. However, the predictive accuracy of drug testing is predicated on 
models that accurately represent the architectural/cellular organization of the tumor and faithfully 
reflect the in vivo biology. We have satisfied many of the requirements of an ideal tumor model 
utilizing resected mesothelial metastases to create the SMART (Sample Microenvironment of 
Resected Metastatic Tumor) System. Multiple solid tumors commonly manifest with metastatic 
disease to the mesothelial surface (peritoneum, pleura, liver capsule) and some are candidates for 
metastasectomy. During these operations, resected tumor-bearing mesothelial tissue is affixed to 
a specialized platform and perfused in a sterile, oxygenated circuit at 370C to maintain normal 
physiologic parameters (Figure 10). Circulating oxygenated perfusate within the system is 
comprised of human plasma (from the patient), DMEM media, antibiotics, insulin (slow infusion).  
 
Figure 10: The SMART System Consisting of SMART Platform 
The SMART platform (Top Left) is designed to mount the human mesothelial tissue containing 
tumor and be suspended in the reservoir of perfusate (Bottom Left), the SMART chamber. The 
chambers suspend maximum of 4 SMART platforms and placed on stir plate in the incubator 
(Middle). The SMART system boasts a physiologic oxygenated perfusion circuit that is suitable to 
keep tissue viable for up to four days. The Right Panel demonstrates the customized holder for each 
SMART platform that is imaged using complex imaging techniques.  
 
We have evaluated gastric adenocarcinoma, pancreatic adenocarcinoma, gastrointestinal stromal 
tumor, and breast adenocarcinoma in the SMART system and documented ex vivo viability at 4 
days with expected immune cell populations, intact architecture, and expected mitotic activity 
(Figure 11A). RNA sequencing was performed as well to compare transcriptomics between Day 


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0 and Day 4. Genes associated with hypoxia, oncogenes/tumor suppressor, cancer stem cells, 
metabolism, and epithelial-mesenchymal transition were isolated from the sequencing data and 
demonstrated conservation of transcriptomics (Figure 11B). These results ultimately demonstrate 
that tumor nodules in their native, functional microenvironment can be preserved ex vivo for 4 
days with fidelity.  
 
Figure 11: Ex Vivo Normal and Tumor Preservation in the SMART System 
A (Left): Demonstration of various histologies on H&E, CD3, CD68 and Ki67 stains on Day 0 and 
Day 4.  
B (Right): Conservation of transcriptomics in hypoxic panel, oncogene/tumor suppressor, cancer 
stem cell, metabolism and EMT panels over breast, gastric, pancreatic and mesothelioma histology. 
 
Due to the translucent nature of the mesothelial tissue, the system is readily amenable to dynamic 
interrogation with confocal, two photon and light sheet microscopy. This avenue of investigation 
is supported by a research collaborative agreement (RCA) with BioLegend and our affiliation with 
CAT-I to develop fluorescently labelled Fab fragment for live cell labelling. For example, with the 
increasing use of checkpoint inhibitors like Pembrolizumab in solid tumors, we decided to evaluate 
the drug in the SMART system using tumor from a patient with gastric adenocarcinoma and a 
patient with colorectal adenocarcinoma. We demonstrated immune cell engagement with tumors 
cells for both gastric and colorectal adenocarcinoma, and captured tumor cell lysis with the latter 
(Figure 12). Such responses at the cellular level are key to understanding why some cells respond 
to the immune system while others are ostensibly resistant. 
As the only currently known platform that has an intact, immunocompotent tumor 
microenvironment, the SMART System allows for the analysis of agents utilizing real controls to 
increase current understandings of the tumor microenvironment. Analyses can be readily imaged 
(taking video up to an hour) to obtain tangible visualizations of the tested agent effects (see 
Figure 12). 
 


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Figure 12: SMART Platforms are Valuable Tools for Drug Evaluations Such as Pembrolizumab 
Left: SMART platforms with peritoneum from a patient with gastric cancer incubated with 
immune checkpoint inhibitor Pembrolizumab for 2 days followed by Alexa488CD44/ 
Alexa594CD45 antibodies. Maximum projections of 2-photon images illustrate the intimate contact 
between CD45-positive cells and the cancer cells.  
Right: Timeseries montage taken from liver capsule tissue mounted on SMART platforms from a 
colorectal cancer patient with liver metastases incubated with 5 g/mL pembrolizumab for 4 hours. 
CD45-positive cells bound to CD44-positive cancer cell undergoing apoptosis. 
 
 
 
2 
ELIGIBILITY ASSESSMENT AND ENROLLMENT 
 
ELIGIBILITY CRITERIA 
2.1.1 Inclusion Criteria 
2.1.1.1 Subjects must have histologically or cytologically confirmed diagnoses of 
adenocarcinoma in one of the following scenarios: 
o Primary tumors of the pancreas 
o Primary tumors of the bile duct and ampulla  
o Metastatic colorectal cancers to the liver  
2.1.1.2 Subjects must have disease resectable with a standard pancreatectomy 
(pancreaticoduodenectomy or distal pancreatectomy) or liver resection.  
2.1.1.3 Subjects may have received prior therapy, including neoadjuvant regimens. 
2.1.1.4 Subjects must have serum CA 19-9 elevations greater than the upper limit of normal but 
less than 2500 U/mL.  
2.1.1.5 Age ≥ 18 years. 
2.1.1.6 ECOG performance status ≤ 1 (Appendix A). 
2.1.1.7 Subjects must have adequate organ and marrow function as defined below:  
o leukocytes  
 
 
> 3,000/mcL 


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41 
 
o absolute neutrophil count  
> 1,500/mcL 
o platelets 
 
 
 
> 90,000/mcL 
2.1.1.8 For subjects with Periampullary cancers that require a pancreaticoduodenectomy for 
complete tumor extirpation: 
o total bilirubin 
 
 
< 10 ULN* 
o AST(SGOT)/ALT(SGPT) 
< 5 X institutional upper limit of normal 
o creatinine  
 
 
< 1.5 X institutional upper limit of normal 
*Subjects with periampullary cancers typically present with biliary obstruction 
resulting in significant abnormalities in liver function tests that do not reflect liver 
dysfunction. These values normalize after tumor removal. They can be normalized pre-
operatively with biliary stenting but several large studies have demonstrated an increase 
in infectious complications with drainage. As such, a practice standard has been to 
avoid stenting until bilirubin level rises above 10 X ULN.  
2.1.1.9 For subjects with liver tumors (cholangiocarcinoma or metastatic colorectal cancer) 
requiring a hepatectomy for complete tumor extirpation: 
o total bilirubin 
 
 
< 2.5 X institutional upper limit of normal* 
o AST(SGOT)/ALT(SGPT) 
< 5 X institutional upper limit of normal* 
o creatinine  
 
 
< 1.5 X institutional upper limit of normal 
*Liver abnormalities in this range are consistent with parenchymal destruction from 
the tumor.  
2.1.1.10 For subjects with pancreas tumors that require a distal pancreatectomy for extirpation: 
o total bilirubin 
 
 
< 1.5 X institutional upper limit of normal* 
o AST(SGOT)/ALT(SGPT) 
< 2 X institutional upper limit of normal* 
o creatinine  
 
 
< 1.5 X institutional upper limit of normal 
*Liver abnormalities in this range are consistent with pancreas cancer destruction from 
the tumor. 
2.1.1.11 The effects of MVT-5873 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 and for the 
duration of study participation and for 3 months after completion of study treatment. 
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. 
2.1.1.12 Ability of subject to understand and the willingness to sign a written informed consent 
document. 
2.1.1.13 Subjects must agree to co-enrollment on the tissue collection protocol 13C0176, 
“Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or 
Surgical Resection of Solid Tumors”. 


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2.1.2 Exclusion Criteria 
2.1.2.1 Presence of disease outside the confines of a standard operation for subjects with peri-
ampullary cancers (pancreatic and cholangiocarcinoma). 
2.1.2.2 Presence of disease outside the liver for subjects with intrahepatic/hilar 
cholangiocarcinoma or metastatic colorectal cancer, other than a primary tumor for 
subjects with metastatic colorectal cancer. 
2.1.2.3 Subjects who are receiving any other investigational agents. 
2.1.2.4 Fewer than 28 days (or 5 half-lives for systemic agents, whichever is shorter) from the 
last day of prior anticancer therapy, including chemotherapy, hormonal, investigational, 
and or biological therapies and irradiation. 
2.1.2.5 Uncontrolled inter-current illness including, but not limited to, ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac 
arrhythmia, or psychiatric illness/social situations that would limit compliance with 
study requirements. 
2.1.2.6 Active concurrent malignancies within the last five years other than the primary tumor 
in subjects with metastatic colorectal cancer, basal or squamous cell skin carcinoma or 
non- medullary thyroid carcinoma. 
2.1.2.7 Pregnant women are excluded from this study because of the potential for teratogenic or 
abortifacient effects of the MVT-5873. Because there is an unknown but potential risk 
for adverse events in nursing infants secondary to treatment of the mother, 
breastfeeding should be discontinued if the mother is treated. These potential risks may 
also apply to other agents used in this study. 
2.1.2.8 Subjects with active, Hepatitis B or C infection because of the potential for increased 
liver toxicity given the damaging effects of the virus. 
2.1.2.9 Allergic to chimeric, humanized or human antibodies. 
2.1.2.10 Received live vaccine within 4 weeks prior to the first date of study intervention. 
2.1.2.11 Infection requiring hospitalization or herpes zoster treatment within 2 weeks prior to the 
first date of study intervention. 
2.1.2.12 Long-term infectious diseases (tuberculosis, fungal infections) active within 2 years 
prior to the first date of study intervention. 
2.1.3 Recruitment Strategies 
This protocol may be abstracted into a plain language announcement posted on NIH websites and 
on NIH social media platforms. This study will also be listed on available websites (e.g., 
www.clinicaltrials.gov) and participants will be recruited from the current patient population at 
NIH. Participants may also be recruited through self-referrals and physician referrals. Dr. 
Hernandez is a member of the clinical trials committee of America’s HepatoPancreatoBiliary 
Association and will also solicit eligible subjects through the organization.  
Advertisements approved under this protocol may be distributed in local media (electronic and 
print) with recruitment efforts focused on, but not limited to, NIH and the greater Washington DC 
area; some recruitment efforts may take place nationwide. 


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SCREENING EVALUATION 
2.2.1 Screening Activities Performed Prior to Obtaining Informed Consent 
Minimal risk activities that may be performed before the subject has signed a consent include the 
following:  
• Email, written, in person or telephone communications with prospective subjects.  
• Review of existing medical records to include H&P, laboratory studies, etc.   
• Review of existing MRI, x-ray, or CT images. 
• Review of existing photographs or videos. 
• Review of existing pathology specimens/reports from a specimen obtained for diagnostic 
purposes. 
A waiver of consent for these activities has been requested in Section 12.5.1. 
2.2.2 Screening Activities Performed After a Consent for Screening Has Been Signed 
The following activities will be performed only after the subject has signed the study consent OR 
the consent for study 01C0129 (provided the procedure is permitted on that study) on which 
screening activities may also be performed. Assessments performed at outside facilities or on 
another NIH protocol within the timeframes below may also be used to determine eligibility once 
a patient has signed the consent. 
Studies should be done within 6 weeks prior to being registered for treatment, unless otherwise 
noted below: 
• History and Physical Examination:  
o Complete medical history and physical examination (including height, weight, vital 
signs, EKG and ECOG performance status). 
• Laboratory Evaluation: 
o CA 19-9 levels 
o Hematological profile: CBC with differential and platelet count.  
o Biochemical profile: electrolytes, BUN, creatinine, AST, ALT, total bilirubin, alkaline 
phosphatase, calcium, phosphorus, albumin, magnesium, amylase.  
o Hep B and C 
o Serum or urine pregnancy test for female participants of childbearing age (in the 
absence of prior hysterectomy), performed within 7 days prior to treatment.  
• CT of chest, abdomen and pelvis. (Note: This scan does not need to be repeated at NIH if 
it has already been done at an external institute within 6 weeks prior to treatment and the 
investigator determines that the scan is of sufficient detail for study diagnostics.) 
• Histologic confirmation by the Laboratory of Pathology, NIH (at any time point prior to 
enrollment). If there is no available tumor sample, biopsy will be performed to confirm the 
diagnosis. 


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• MRI (for subjects with liver disease). (Note: This scan does not need to be repeated at NIH 
if it has already been done at an external institute within 6 weeks prior to treatment and the 
investigator determines that the scan is of sufficient detail for study diagnostics.) 
 
PARTICIPANT REGISTRATION AND STATUS UPDATE PROCEDURES 
Registration and status updates (e.g., when a participant is taken off protocol therapy and when a 
participant is taken off-study) will take place per CCR SOP ADCR-2: CCR Participant 
Registration & Status Updates found here. 
2.3.1 Treatment Assignment and Randomization/Stratification Procedures 
2.3.1.1 Cohorts 
Number Name 
Description 
1 
Cohort 1 
Subjects with pancreatic cancer, cholangiocarcinoma or metastatic 
to the liver colorectal cancer, having low elevated LFTs (AST/ALT 
≤ 2 X ULN and/or bilirubin ≤ 1.5 X ULN), enrolled into pre-
operative MVT-5873 escalation dose levels. 
2 
Cohort 2 
Subjects with pancreatic cancer, cholangiocarcinoma or metastatic 
to the liver colorectal cancer, having moderate elevated LFTs (LFTs 
above what is required for Cohort 1 AND AST/ALT < 5 X ULN 
and/or bilirubin ≤ 3 X ULN), enrolled into pre-operative MVT-5873 
escalation dose levels. 
3 
Cohort 3 
Subjects with pancreatic cancer enrolled at the pre-operative 
recommended dose (RD) of MVT-5873. 
4 
Cohort 4 
Subjects with cholangiocarcinoma enrolled at the pre-operative 
recommended dose (RD) of MVT-5873. 
5 
Cohort 5 
Subjects with metastatic to the liver colorectal cancer enrolled at the 
pre-operative recommended dose (RD) of MVT-5873. 
2.3.1.2 Arms 
Number Name 
Description 
1 
Arm 1 
Pre-operative escalation doses of MVT-5873, pancreatectomy or 
hepatectomy and post-operative MVT-5873 treatment.   
2 
Arm 2  
Pre-operative RD of MVT-5873, pancreatectomy or hepatectomy 
and post-operative MVT-5873 treatment. 
2.3.1.3 Arm Assignment 
Subjects in Cohorts 1 and 2 will be directly assigned to Arm 1. 
Subjects in Cohorts 3-5 will be directly assigned to Arm 2.  


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BASELINE EVALUATION 
Tests listed below that were performed within the appropriate timeframe at screening need not be 
repeated. 
Within 3 weeks prior to study intervention unless otherwise indicated: 
• Complete physical examination (including weight, vital signs, EKG and ECOG 
performance status). 
• Laboratory Evaluation: 
o CA 19-9 levels 
o Hematological profile: CBC with differential and platelet count.  
o Biochemical profile: electrolytes, BUN, creatinine, AST, ALT, total bilirubin, alkaline 
phosphatase, calcium, phosphorus, albumin, magnesium, amylase.  
o PT/PTT/INR 
o Serum or urine pregnancy test for female participants of potential childbearing age (in 
the absence of prior hysterectomy), performed within 3 days prior to resection. 
• CT of chest, abdomen and pelvis  
• MRI (for subjects with liver disease) 
• Concomitant medications 
• Baseline adverse events 
3 
STUDY IMPLEMENTATION 
 
STUDY DESIGN 
This is a trial designed to determine if perioperative MVT-5873 is safe and effective for subjects 
with operable cancers of the pancreas and liver.  
Eligible candidates will receive one dose of MVT-5873 (1 mg/kg (DL1) or 3 mg/kg (DL2) 3 days 
prior to resection (Day -3) as part of the safety lead-in cohorts (Cohorts 1 and 2). See Table 9 
below for expected course. 
Once the pre-operative safe dose of MVT-5873 is identified, additional subjects will be evaluated 
within the treatment cohorts (Cohorts 3-5) at that MTD.  
Resection will be undertaken to remove all demonstrable disease in the liver, bile ducts and 
pancreas on Day 0. The operation may be delayed for up to 4 days until any AST/ALT elevations 
are ≤ 10 X ULN, and Bilirubin is ≤ 2 X the baseline value or < 3 X ULN. All subjects will start 
post-operative infusions of MVT-5873 (1 mg/kg) in cycles consisting of 21 days.  During Cycle 
1, subjects will receive 2 weekly infusions of MVT-5873 (on Day 1 and Day 8). During Cycle 2, 
subjects will receive an infusion of MVT-5873 every 2 weeks (Day 1 and Day 15). Evaluations 
will be performed on C1D1, C1D8, C2D1 and C2D15 (+/- 48 hours) as indicated in Section 3.4. 
Cycle 1 Day 1 will be on any day between Day 4 and Day 10 after surgery, when AST/ALT 
elevations ≤ 10 X ULN and decreasing for 2 consecutive days, and Bilirubin ≤ 2 X ULN or 


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decreasing for 2 consecutive days. If LFTs do not decrease as described within 14 days after 
surgery, patient will be taken off treatment.  
Treatment with MVT-5873 will continue until off treatment criteria are met.  
Table 9: Safety Lead-In Study Design 
Pre-operative Dose 
Operation 
Weekly dosing 
Q2 Weekly dosing 
Day -3 
Day 0 
Cycle 1:  
Days 1 and 8 
Cycle 2:  
Days 1 and 15  
DL1 
MVT-5873  
1 mg/kg 
Pancreatectomy 
or Hepatectomy 
1 
mg/kg 
MVT-
5873* 
1 mg/kg MVT-5873* 
DL2 
MVT-5873 
3 mg/kg 
* Post-operative infusions of MVT-5873 will consist of 1 mg/kg in all cycles. MVT-5873 dose 
variability is only within the single pre-operative dose.   
3.1.1 Dose Limiting Toxicity 
The DLT period is 10 days after pre-operative MVT-5873 treatment.  
Any Grade ≥ 3 adverse event (AE), occurring during the DLT evaluation period, possibly or 
definitely attributed to MVT-5873 with the exception of: 
• Bilirubin < 6X ULN if resolved to < 3 or ≤ 2X the baseline in 7 days after first MVT-5873 
treatment. 
• AST/ALT < 20X ULN if resolved to < 10X ULN in 7 days after first MVT-5873 treatment. 
Resection will be undertaken to remove all demonstrable disease in the liver, pancreas or bile ducts 
on Day 0.  
Note: The operation may be delayed until AST/ALT elevations are ≤ 10X ULN, and Bilirubin is 
≤ 2X the baseline value or < 3X ULN. If the operation is delayed for more than 4 days due to 
failure of LFT to fall within the values outlined above, this will be considered DLT. 
3.1.2 Safety Lead-In Cohorts 
In order to minimize patient risk, we will initially accrue six (6) subjects sequentially in two safety 
lead-in cohorts based upon AST/ALT/Bili abnormalities and irrespective of tumor histology.   
For each safety lead-in cohort we will evaluate two dose levels, 1 mg/kg and 3 mg/kg as 
summarized in Table 10 below.   
The safety lead-in continues until at least two subjects among the cohort of six subjects experience 
dose-limiting toxicities (ie, ≥33% of subjects with a dose-limiting toxicity at that dose level).   
If none (0) or one (1) of the six subjects at 1 mg/kg experiences a dose-limiting toxicity, then 
escalation to 3 mg/kg may proceed within each safety lead-in cohort and 1 mg/kg is deemed safe. 


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If none (0) or one (1) of the six subjects experiences a dose-limiting toxicity at 3 mg/kg within 
each safety lead-in cohort,  then 3 mg/kg is deemed safe at the respective safety lead in cohort. 
Dose esclation maximum will be 3 mg/kg. 
Table 10: Safety Lead-In Cohorts 
LFT 
Safety Lead-In 
Cohort 1 (Low elevated LFTs) 
N=6 
Safety Lead-In 
Cohort 
2* 
(Moderate 
elevated 
LFTs) 
N=6 
AST/ALT ≤ 2X ULN, and/or 
< 5X ULN, and/or 
Bilirubin 
≤ 1.5X ULN 
≤ 3X ULN 
*LFTs above what is required for Cohort 1 AND AST/ALT < 5X ULN and/or bilirubin ≤ 3X ULN.  
Note: LFTs determined at screening for cohort assignment.   
Every subject of each safety lead-in cohort will be observed for at least 10 days after first dose of 
MVT-5873 before the subsequent subject can be treated. 
Subjects who do not complete the DLT observation period for reasons other than a DLT will be 
replaced and will not be included in the response evaluation. 
Intra-patient dose de-escalation is not permitted for subjects enrolled in the safety lead-in cohorts. 
Subjects will receive assigned dose and in case of DLT will be taken off protocol. Every subject 
enrolled onto safety lead-in cohorts will be part of the DLT evaluation of its respective dose level. 
Subjects who experience DLT after pre-operative dose of MVT-5873 may have surgery when DLT 
is resolved and will be taken off MVT-5873 treatment after operation (see Section 3.5 for surgical 
guidelines and post-operative care).  
 
Safety Lead-In Cohort 1 (Low Elevated LFTs) 
Cohort 1 Dose Level 1 (1 mg/kg)  
Six (6) subjects will be enrolled at Dose Level 1, treated with MVT-5873 (1 mg/kg on Day -3) 
and have surgery on Day 0.  
If two (2) subjects experience a DLT during DLT period at dose level DL1, no further attempts at 
completing the safety run-in of MVT-5873 in combination with surgery will be conducted, and 
the trial will be closed to accrual. 
If < 2 of 6 subjects experience DLT during DLT period, DL1 will be considered to be safe to use 
in subjects with low elevated LFTs and enrollment into Cohort 2 will begin at DL1.  Concurrently, 
enrollment into Cohort 1 Dose Level 2 will begin. 
 
Cohort 1 Dose Level 2 (3 mg/kg) 


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Six (6) subjects will be enrolled at Dose Level 2, treated with MVT-5873 (3 mg/kg on Day -3) 
and have surgery on Day 0.  
If two (2) subjects experience a DLT during DLT period at dose level DL2, no further attempts at 
completing the safety run-in at DL2 will be conducted at trial will continue with DL1 only. 
If < 2 of 6 subjects experience DLT during DLT period, DL2 will be considered to be safe to use 
in subjects with low elevated LFTs.  
 
Safety Lead-In Cohort 2 (Moderate elevated LFTs) 
Cohort 2 Dose Level 1 (1 mg/kg) 
If DL1 is proved to be safe in Cohort 1 Dose Level 1, 6 subjects will be enrolled in Cohort 2 Dose 
Level 1. Subjects will be treated with MVT-5873 (1 mg/kg on Day -3) and have surgery on Day 
0.  
If two (2) subjects experience a DLT during DLT period at dose level DL1, no further attempts at 
completing the safety run-in of MVT-5873 in combination with surgery in subjects with moderate 
elevated LFTs will be conducted. 
If < 2 of 6 subjects experience DLT during DLT period, DL1 will be considered to be safe to use 
in subjects with moderate elevated LFTs. 
If DL1 is safe to use in subjects with moderate elevated LFTs, 6 subjects will be enrolled at Dose 
Level 2 in Cohort 2.  
 
Cohort 2 Dose Level 2 (3 mg/kg) 
Six (6) subjects will be treated with MVT-5873 (3 mg/kg on Day -3) and have surgery on Day 0.  
If two (2) subjects experience a DLT during DLT period at dose level DL2, no further attempts at 
completing the safety run-in at DL2 will be conducted at trial will continue with DL1 only. 
If < 2 out of 6 experience DLT during DLT period, DL2 will be considered to be safe to use in 
subjects with moderate elevated LFTs. 
3.1.3 Treatment Cohorts 
3.1.3.1 Treatment Cohorts at Pre-Operative MTD 
Once the pre-operative safe dose of MVT-5873 and allowed elevated level of LFTs is estimated, 
additional subjects will be evaluated at that MTD (see Table 11) within Cohorts 3-5.   
Treatment subjects will be accrued with the following histologies: 
o Metastatic Colorectal Cancer (n=24) 
o Cholangiocarcinoma (n= 24) 
o Pancreatic Cancer (n=23)  
Note: Subjects treated during the safety lead-in (Cohorts 1 and 2) will complete the study as 
indicated in Sections 3.1.2 and 3.5. 


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Table 11: Treatment Study Design 
Pre-operative Dose 
Operation 
Weekly dosing 
Q2 Weekly dosing 
Day -3 
Day 0 
Cycle 1:  
Days 1 and 8 
Cycle 2:  
Days 1 and 15  
MVT-5873 at MTD 
Pancreatectomy 
or Hepatectomy 
1 
mg/kg 
MVT-
5873* 
1 mg/kg MVT-5873* 
3.1.3.2 Treatment Cohorts at Two Different Pre-Operative MTDs by LFT Elevation are 
Determined from Safety Lead-In 
If  two different pre-operative safe doses of MVT-5873 are determined from the safety lead-in 
due to the difference of LFT elevation, subjects within the treatment cohorts will each be treated 
by their elevated level of LFTs as identified at screening (refer to Table 12 and  
Table 13).  
Table 12: Treatment Guidelines (If Two Different Pre-Operative MTDs by LFT Elevation are 
Determined from Safety Lead-In) 
Treatment  
Cohorts 
Low elevated LFTs 
(AST/ALT ≤ 2X ULN and/or 
bilirubin ≤ 1.5X ULN) 
Moderate elevated LFTs 
(LFTs above what is required for 
Cohort 1 AND AST/ALT < 5X ULN 
and/or bilirubin ≤ 3X ULN) 
Cohorts 3-5 
 
MVT-5873 at  
Low elevated LFTs MTD 
MVT-5873 at  
Moderate elevated LFTs MTD 
Note: LFTs determined at screening. 
* Baseline LFTs for a subject may be used if the subject’s screening and baseline LFTs are different 
and the change is determined by the PI to be clinically indicated. 
 


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Table 13:Treatment Study Design (If Two Different Pre-Operative MTDs by LFT Elevation are 
Determined from Safety Lead-In) 
Pre-operative Dose 
Operation 
Weekly dosing 
Q2 Weekly dosing 
Day -3 
Day 0 
Cycle 1:  
Days 1 and 8 
Cycle 2:  
Days 1 and 15  
Low 
elevated 
LFTs 
MVT-5873 at  
Low elevated 
LFTs MTD 
Pancreatectomy 
or Hepatectomy 
1 
mg/kg 
MVT-
5873* 
1 mg/kg MVT-5873* 
Moderate 
elevated 
LFTs 
MVT-5873 at  
Moderate 
elevated LFTs 
MTD 
* Post-operative infusions of MVT-5873 will consist of 1 mg/kg in all cycles. MVT-5873 dose 
variability is only within the single pre-operative dose.   
 
STUDY DRUG ADMINISTRATION 
3.2.1 Preparation and Administration of MVT-5873 
MVT-5873 is provided as a single-use vial containing 3.0 mL of sterile solution at 10 mg/mL in a 
buffer at pH 6.0, containing 25 mM histidine, 150 mM sucrose, 55 mM sodium chloride, and 
0.02% polysorbate 80. 
Prior to infusion, MVT-5873 is diluted in normal saline to obtain a final concentration of less than 
5 mg/mL. The administration apparatus must include a 0.2-micron inline filter. 
3.2.2 Stability of MVT-5873 Following Preparation 
MVT-5873 should be administered within 24 hours of preparation. 
3.2.3 Upper Limit to Administered Dose in Obese Subjects 
In subjects who weigh more than 100 kg (220 pounds), the administered dose should be calculated 
based on a theoretical weight of 100 kg. 
3.2.4 Infusion Rate of MVT-5873 
The first dose of MVT-5873 for each subject will be administered as an intravenous infusion over 
at least 120 minutes. In subjects who tolerate an initial infusion without difficulty, subsequent 
infusions may be reduced by 30 minutes to a minimum infusion duration of 60 minutes (i.e., a 120-
minute infusion during the first infusion, a 90-minute infusion during the second infusion, a 60-
minute infusion during the third and subsequent infusions). The duration of infusion for MVT-
5873 should never be less than 60 minutes. 
Vital signs will be taken pre-and post-MVT-5873 administration. 


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3.2.5 Treatment Guidelines for MVT-5873-Related Infusion Reaction 
Please refer to table, Treatment Guidelines for MVT-5873-Related Infusion Reaction, for 
guidance on managing infusion related reactions during MVT-5873 administration.  
Treatment Guidelines for MVT-5873-Related Infusion Reaction 
Grade 
(CTCAEv4) 
Definition 
Treatment Guideline 
1 
Mild transient reaction; infusion 
interruption not indicated; 
intervention not indicated 
Monitor for at least 2 hours (120 minutes) 
after end of infusion; provide patient 
instructions and prophylactic medications 
at discharge as appropriate 
2 
Therapy or infusion interruption 
indicated but responds promptly to 
symptomatic treatment 
Infusion may be restarted once following 
a minimal 60-minute delay. A second 
infusion interruption requires 
discontinuation of MVT-5873 
administration. 
Administration of medications (e.g., anti-
histamines, steroids, NSAIDS and IV 
fluids etc.) as appropriate; monitor in 
clinic for at least 2 hours (120 minutes) 
after completion of infusion; provide 
prophylactic medications as appropriate 
for subsequent MVT-5873 doses 
3 
Prolonged (e.g., not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms following 
initial improvement, 
hospitalization indicated for 
clinical sequelae 
Administration of medications (e.g., anti-
histamines, steroids, NSAIDS and IV 
fluids etc.) as appropriate; hospitalization 
for medical care and observation; 
Discontinue MVT-5873 permanently  
4 
Life-threatening consequences; 
urgent intervention indicated 
Hospitalization for urgent medical 
treatment; Discontinue MVT-5873 
permanently 
3.2.6 Premedication 
Subjects should receive their initial dose of MVT-5873 in the absence of premedication. In subjects 
who experience infusion reactions that are manageable and allow for additional administration of 
MVT-5873, premedication may be administered for subsequent doses consistent with institutional 
guidelines. 


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Starting in February 2017 (as documented in the MabVax 0715 Clinical Study Note to File dated 
13-Feb 2017), the Safety Committee allowed for the use of prophylactic medications for the 
control of infusion reactions. The recommended dose was 12 – 20 mg of decadron IV at least 30 
minutes prior and 4 mg BID PO of decadron for two days following each MVT-5873 
administration. The investigator was free to manage the taper of decadron in those subjects who 
did not demonstrate infusion reactions. 
 
DOSE MODIFICATIONS 
Adverse Events: All adverse events in this trial will be graded using the NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.0 - a complete listing is available at 
the CTEP website: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.  
Dose adjustments for pre-operative MVT-5873 are explained in Section 3.1.2. 
Summary of dose holding/interruptions for MVT-5873 in case of MVT-5873-related adverse 
events (graded according to NCI-CTCAE v5.0). 
 
General Adverse Events 
Action 
Non-hematological, Grade 1 or 2 
Continue MVT-5873 therapy at full dose prescribed. 
Apply maximum supportive care recommendations.  
If prolonged duration of Grade 2 adverse event (≥ 7 
days) 
is 
affecting 
quality 
of 
life, 
consider 
discontinuation of the drug. 
Non-hematological, Grade 3 or 4 
(excluding cardiac and hepatobiliary 
events) 
Apply maximum supportive care recommendations. 
Hold MVT-5873 therapy until recovery to Grade ≤ 1 
(up to 14 days).  
For Grade 3 or 4 interstitial pneumonitis or Grade 3 or 
4 rash manifested as toxic epidermal necrolysis (e.g. 
Stevens-Johnson Syndrome etc.) MVT-5873 must be 
discontinued. 
If recurrence of adverse event after drug hold/ 
interruptions is observed, and maximum supportive 
care measures applied, hold drug once again until 
recovery to Grade ≤ 1 (up to 14 days).  If no recovery, 
consider discontinuation of the drug. 
Non-hematological, Grade 3 or 4 
adverse events NOT resolved to 
Grade ≤ 1 within a maximum of 2 
weeks 
from 
last 
planned 
administration  
Action (discontinue or resume MVT-5873 therapy) in 
individual cases after discussions with the Sponsor. 
 


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General Adverse Events 
Action 
Cardiac Adverse Events 
 
Cardiac (Severity corresponding to 
NYHA criteria) 
MVT-5873 therapy to be discontinued permanently in 
case of symptomatic NYHA class III and IV CHF. 
MVT-5873 therapy to be held, continued, or resumed 
accordingly for subjects with NYHA class I or II CHF. 
Hepatobiliary Adverse Events 
 
Grade 1-2 bilirubin or Grade 1-2 
AST/ALT 
Continue MVT-5873 therapy at full dose prescribed. 
Apply maximum supportive care recommendations. 
Grade 3 bilirubin or Grade 3 
AST/ALT  
Apply maximum supportive care recommendations. 
Hold MVT-5873 therapy until recovery to Grade < 1 
If not resolved for 14 days, discontinue treatment. 
Grade 2 bilirubin and Grade 3 
AST/ALT 
Grade 4 events 
*Discontinue MVT-5873 
*Unless Surgery-related cause 
Note: In case of multiple short interruptions of dose due to either adverse events or drug 
supply or other reasons the sum of days without MVT-5873 treatment should not exceed 28 
days between two treatments or in any 90-day treatment period.  


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STUDY CALENDAR 
 
Screening1  
 
Baseline1 
 
D-3 
 
D01 
Cycle 1 
Cycle 2 
EOT2 
Safety 
FU3 
Long 
Term 
FU4 
D15 
D8 
D1 
D15 
MVT-5873  
 
 
X 
 
X 
X 
X 
X 
 
 
 
Surgery 
 
 
 
X 
 
 
 
 
 
 
 
Informed Consent  
X 
 
 
 
 
 
 
 
 
 
 
Medical History  
X 
 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Adverse Event Evaluation  
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Physical Exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height  
X 
 
 
 
 
 
 
 
 
 
 
EKG 
X 
X 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Performance Status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
CBC w/Differential, Platelets  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
PT, INR, PTT 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Serum Chemistry6  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
CA 19-97 
X 
X 
X7 
X 
X7 
X7 
X7 
X7 
X 
X 
X 


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Screening1  
 
Baseline1 
 
D-3 
 
D01 
Cycle 1 
Cycle 2 
EOT2 
Safety 
FU3 
Long 
Term 
FU4 
D15 
D8 
D1 
D15 
Hepatitis B and C Serology and/or 
Viral Load  
X 
 
 
 
 
 
 
 
 
 
 
Radiologic Evaluation8  
X 
X 
 
 
X 
X 
X 
X 
X 
 
 
Serum or Urine Pregnancy Test 
X 
X 
 
 
 
 
 
 
 
 
 
Confirmation of dx by NCI LP 
X 
 
 
 
 
 
 
 
 
 
 
Tissue Collection for Research 
 
 
 
X 
 
 
 
 
 
 
 
Research Blood Collection (see 
Section 5.1)  
 
 
X 
X 
X 
 
 
 
X 
 
 
Annual Telephone or Other NIH 
Approved Remote Platforms 
Contact 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 


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1 Day 0 operation may be delayed for 4 days until AST/ALT elevations are ≤ 10X ULN, and Bilirubin is ≤ 2X the baseline value or < 3X ULN. 
2 Day 7 (+/-7 days) after treatment discontinuation. If patient is taken off treatment on the day of regular visit to Clinical Center, this day will be 
EOT visit. 
3 Safety Follow Up visits/labs will occur if patient is agreeable to coming back and physically able to return for the visit. This visit should occur 
around Day 28 post the last dose of study drug. If toxicities cause discontinuation of therapy, subjects will be followed until resolution of toxicity 
to at least Grade 1. If the patient cannot return to the Clinical Center for this visit, a request will be made to collect required clinical labs from a 
local physician or laboratory (as these are routine, standardized laboratory tests, interlaboratory variability is not a concern). If this is not possible, 
subjects may be assessed by telephone or other NIH approved remote platforms for symptoms. 
4 Follow-up will be telephone or other NIH approved remote platforms contact of patient or medical oncologist every 4 months (+/- 2 weeks) to 
assess disease and survival status. Medical records from visits done with the home physician may be securely sent to the study team per CC policy 
and procedures. 
5 Cycle 1 Day 1 will be on any day between Day 4 and Day 10 after surgery, when AST/ALT elevations ≤ 10 X ULN and decreasing for 2 
consecutive days, and Bilirubin ≤ 2 X ULN OR decreasing for 2 consecutive days. 
6 Electrolytes, BUN, creatinine, AST, ALT, total bilirubin, alkaline phosphatase, calcium, phosphorus, albumin, magnesium, amylase. 
7 Serum CA19-9 collection pre-dose and 2 hours post dose (+30 minutes) as noted in treatment cycles. 
8 Evaluations will be performed on C1D1, C1D8, C2D1 and C2D15 (+/- 48 hours) and EOT. CT scan of chest, abdomen and pelvis in all 
subjects. MRI with contrast for subjects with liver disease. Note: Exceptions for the use of contrast during this MRI may be made using the 
best clinical judgement of the investigator. 
 
 


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SURGICAL GUIDELINES 
Pancreas tumors will be extirpated according to standard practice. Resections involving the 
pancreas may require either a pancreaticoduodenectomy or distal pancreatectomy, with or without 
splenectomy. Liver operations will be undertaken according to practice norms. 
3.5.1 Preoperative Patient Management 
Subjects will receive standard preoperative care as appropriate to the planned surgical intervention 
and the patient’s underlying health status. This will include: 
• Clear liquid-diet the evening prior to operation, without additional bowel preparation. 
• Hibiclens shower the night before operation. 
• CA 19-9 levels will be drawn the morning of the procedure. 
• 20 mL of peripheral blood will be drawn prior to induction of anesthesia for circulating 
tumor cell acquisition and analysis (see Section 5.2.6).  
• Preoperative IV antibiotics administered in pre-op holding. 
• Subcutaneous heparin administration for venous thromboembolism prophylaxis just prior 
to operation start. 
• Sequential compression devices will be placed on the lower extremities prior to induction 
of general anesthesia. 
3.5.2 Patient Management in the Operating Room 
3.5.2.1 At Operation: 
• Subjects will undergo a midline line or sub-costal incision. A thorough examination of the 
abdomen will ensue to rule-out occult metastatic disease on the peritoneal surfaces, or 
unrecognized suspicious lymphadenopathy. The operation will then be carried out 
according to standard practice.  
• Prior to tumor extirpation, a 24-gage needle will be used to draw 20 mL of blood from the 
portal vein OR suprahepatic vena cava.   
• Normal liver core biopsies and excisional biopsies will take place for exploratory endpoints 
but will not exceed 100 grams. 
 


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Figure 13: Operating Room Workflow  
3.5.3 Postoperative Care 
3.5.3.1 Patient Monitoring 
• The subjects will be monitored in the ICU or on the surgical ward per routine. 
• On the ward, vital signs (blood pressure, temperature, pulse, respirations) will be taken per 
routine (every 2-6 hours and as clinically indicated).  
• Subjects will receive routine post-operative care; early ambulation will be encouraged. 
Note: Other standard of care may be performed as deemed clinically necessary by the PI. 
• Laboratory evaluations will include:  
o CBC, platelets, acute care, mineral and hepatic panel on post-operative Days  
1 through 7, and then as clinically indicated until discharge.  
o Subjects will be transfused as appropriate to maintain a hemoglobin greater than or 
equal to 8 g/dl. 
3.5.4 Discharge 
• Total hospitalization may be approximately 7-14 days.  
Subjects who are discharged within this time frame should be able to tolerate an oral diet 
with or without dietary supplements. 
 
PATHOLOGICAL EVALUATION  
The histopathologic evaluation, in addition to standard practice of lymph nodes, margin status, etc, 
will involve an evaluation by a third party laboratory for antibody/tumor cell binding (Figure 14 
top image) and a detailed evaluation of the liver parenchyma under the supervision of Dr. David 
Kleiner (Figure 14 bottom image). The liver parenchyma evaluation will include standard 
immunohistochemical agents as well as any special evaluative measures as deemed necessary by 
Dr. Kleiner. 


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Figure 14: Pathologic Evaluation of Tumor and Liver Tissue Removed at the Time of Surgery  
 
 
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 
approximately 28 days following the last dose of study therapy. 
3.7.1 Criteria for Removal from Protocol Therapy 
• Excessive toxicity (see Sections 3.1.1 and 3.3). 
• Completion of 2 cycles of post-operative MVT-5873 treatment. 
• Recurrent disease. 
• CA 19-9 level > 2 X the lowest recorded post-operative dose AND > ULN. 
• Participant requests to be withdrawn from active therapy. 
• Investigator discretion. 
• Positive pregnancy test. 
• Start of standard adjuvant chemotherapy (per medical oncologist decision). Note: 
Patients need to be removed from therapy so that MVT-5873 will not be given within 
2 weeks of the planned start date for adjuvant chemotherapy. 
• Elapse of > 84 days from the start of Day 1, Cycle 1. 


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3.7.2 Off-Study Criteria 
• Participant requests to be withdrawn from study. 
• Death. 
• Investigator discretion. 
• Loss of follow up. 
• PI decision to end the study. 
• Screen failure. 
4 
CONCOMITANT MEDICATIONS/MEASURES 
During the post-operative period, subjects will receive all standard of care supportive measures, 
including possible nasogastric tube drainage and bowel rest for ileus, pulmonary toilet teaching 
and incentive spirometry to prevent atelectasis, transfusions, and antibiotics as indicated. During 
receipt of study drug, standard adjunctive medications inclusive of anti-emetic, anti-nausea and 
bowel function therapy will be employed.  
5 
BIOSPECIMEN COLLECTION 
 
SPECIMEN COLLECTION TABLE 
Test/Assay 
Volume 
Blood 
(approx.) 
Type of 
Tube 
Collection 
Points  
(+/-48hrs) 
Location of 
Specimen 
Processing/ 
Storage 
Location of 
Specimen 
Analysis 
Circulating 
Tumor Cell 
Analysis  
20 mL 
CellSave 
Preservati
on Tubes 
D-3, D0 & 
C1D1 
(Delivered by 
study team to) 
Trepel Lab 
Trepel Lab 
Monocyte 
Phagocyte 
System 
(MPS) 
Profiling 
17 mL 
SST 
D-3 & D0 
Hernandez Lab 
for 
storage 
until shipment 
Zamboni Lab at  
UNC Chapel Hill 
 
Biomarker 
Studies  
10 mL 
EDTA 
(Lavender) 
D-3, D0, 
C1D1 & 
EOT 
Hernandez Lab 
(Blood 
Processing 
Core (BPC) as 
necessary, see 
Section 5.2.1) 
Hernandez Lab 


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Metastasis 
Assays Using 
Ex Vivo 
Perfusion of 
Omentum 
Omentum 
N/A 
D0 (at time 
of surgery) 
(Immediately 
to)  
Hernandez Lab 
Hernandez Lab 
Ex Vivo 
Hepatic 
Perfusion 
Models 
Tumor 
tissue 
N/A 
D0 (at time 
of surgery) 
(Immediately, 
when 
necessary)  
Hernandez Lab 
Hernandez Lab 
Proteogenomi
c Analysis 
Tumor 
tissue 
with 
mesothelial 
metastases 
 
N/A 
D0 (at time 
of surgery) 
Hernandez Lab 
(Blood 
Processing 
Core (BPC) as 
necessary, see 
Section 5.2.1) 
Hernandez Lab 
 
Drug 
Penetration 
Analysis 
Tumor 
tissue 
N/A 
D0 (at time 
of surgery) 
Hernandez Lab 
(Blood 
Processing 
Core (BPC) as 
necessary, see 
Section 5.2.1) 
Hernandez Lab 
RNA 
Analysis 
10 mL 
EDTA 
(Lavender) 
D0 
Hernandez Lab 
for storage 
until shipment 
(by study 
team) 
Genomic 
Expression 
RNA-Seq 
Tumor 
tissue  
(and 
normal 
tissue, as 
available) 
N/A 
D0 (at time 
of surgery) 
Hernandez Lab 
for storage 
until shipment 
(by study 
team) 
Genomic 
Expression 
 


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CORRELATIVE STUDIES FOR RESEARCH/PHARMACOKINETIC STUDIES 
5.2.1 Tumor and Tissue Collection 
Tumor and normal tissue samples will be collected at the time of surgery. Tissue will only be taken 
for research purposes after it is removed as part of the standard operation, as viable tissue that will 
otherwise be removed as part of the operation, or as core needle biopsies of normal liver for 
subjects undergoing pancreatectomies. The total amount of normal liver tissue removed for 
research purposes will not exceed 100 grams. 
Some of the samples will be immediately used in the Dr. Hernandez’s lab (see Section 5.3.4 
below), and the rest will be sent for barcoding and initial storage to Blood Processing Core (BPC) 
as necessary per PI instruction. 
RNA-Seq data will be analyzed for correlation with recurrence patterns. The analysis will utilize 
logistic regression and corrections for false discovery (5%). The analysis will be undertaken in 
conjunction with the Branch’s bioinformatics specialist. 
5.2.2 RNA Evaluation 
Tumor and normal tissue samples (coded-linked) will be sent to Genomic Expression for RNA 
analysis under MTA (Section 11.1): 
Gitte Pedersen, CEO 
Genomic Expression, Inc.  
100 Cummings Center, Suite 451C 
Beverly, MA 01915 
Phone: 203-812-0690 
Email: glp@genomicexpression.com  
 
Samples sent to Genomic Expressions for RNA analysis will be coded before shipment. 
Genomic Expression has reengineered quantitative RNA sequencing for clinical applications, with 
the goal of enabling oncologists to routinely use tumor gene expression profiles to help select the 
best treatment options for their subjects. OneRNA, the proprietary platform from Genomic 
Expression, uses a novel approach to prepare sequencing libraries from tumor messenger RNA. 
The OneRNA library preparation technology, generates a library of nucleic acid tags from the 3’ 
ends of mRNA molecules. These tag libraries can be “read out,” meaning sequenced and counted, 
on next generation sequencers. This method reduces the number of reads to detect weakly 
expressed genes by 5- to 10-fold and simplifies the generation of a global expression profile from 
the sequencing data. OneRNA proprietary sample prep is integrated with proprietary analytics. 
After correcting for PCR duplicates, the sequenced tags are mapped to the human genome and/or 
transcriptome and compiled into gene expression profiles. Tumor expression profiles are 
normalized alongside normal tissue expression profiles to put them on a common scale. Using 
outlier detection methods, over and under expressed genes are identified by comparing the 
expression level of each gene in the tumor to the distribution of expression levels for that same 
gene in normal tissue(s). 


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5.2.3 Metastasis Assays Using Ex Vivo Perfusion of Omentum 
For instances in which a standard Whipple procedure is done, omentum obtained from the 
operating room (as part of the standard Whipple procedure) will be immediately transported to Dr. 
Hernandez’s lab. The gastroepiploic arterial arcade will be cannulated and the omentum kept 
viable using Dr. Hernandez’s Liver Assist Device (Figure 4 bottom).  
5.2.4 Ex Vivo Hepatic Perfusion Model 
Resected tumor-bearing liver and pancreas will be perfused through native blood vessels in order 
to develop ex vivo models for pancreatic cancer, cholangiocarcinoma, and metastatic colorectal 
cancer as indicated in Section 1.2.11.  
 
 
Figure 15: Scientific Endpoints. Evaluation of Circulating Tumor Cells (top) and Ex Vivo Tissue 
Modeling (bottom) 
5.2.5 Circulating Tumor Cell Evaluation 
Blood will be collected for circulating tumor cell (CTC) assays to be performed in the Dr. Trepel 
Laboratory (Developmental Therapeutics Branch, CCR). 
Peripheral blood will be drawn from a peripheral vein and the portal or supra-hepatic IVC (intra-
op) for enumeration and characterization of CTCs. CTCs will be assessed using ferrofluidic 
enrichment and multiparameter flow cytometric detection. CTCs will be identified as viable, 
nucleated cells, that positively express one or more epithelial or tumor markers and are negative 
for expression of hematopoietic markers. The number of CTCs in peripheral blood will be counted.   
In addition to quantification, we will evaluate CTCs for CA 19-9 expression using flow cytometry.  


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5.2.6 Monocyte Phagocyte System (MPS) Profiling 
Blood will be collected for monocyte phagocyte system (MPS) profiling, to be performed in the 
Zamboni Laboratory – University of North Carolina at Chapel Hill. MPS profiling will be used to 
evaluate the impact of MVT-5873 therapy on circulating tumor cells. 
Coded linked samples will be sent to Dr. Zambroni at the Zamboni Laboratory under MTA (see 
Section 11.1): 
Zamboni Laboratory – UNC at Chapel Hill 
Attn: Andrew Lucas 
120 Mason Farm Road 
1022A Genetic Medicine Building, CB#7361 
Chapel Hill, NC  27599 
Lab Phone: (919) 966-1622 
 
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 appropriate approvals and/or agreements, if required. 
Tissue samples will be sent to Blood Processing Core (BPC) for barcoding and initial storage until 
they are distributed to Dr. Hernandez for sample analysis as described in the protocol.  
5.3.1 Samples Managed by the Blood Processing Core (BPC)  
5.3.1.1 BPC Contact Information  
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. 
5.3.1.2 Sample Data Collection 
All samples sent to the Blood Processing Core (BPC) will be barcoded, with data entered and 
stored in the Labmatrix utilized by the BPC. This is a secure program, with access to Labmatrix 
limited to defined Figg lab personnel, who are issued individual user accounts. Installation of 
Labmatrix is limited to computers specified by Dr. Figg. These computers all have a password 
restricted login screen.  
Labmatrix creates a unique barcode ID for every sample and sample box, which cannot be traced 
back to subjects without Labmatrix 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. Patient demographics associated with the clinical center patient 
number are provided in the system. For each sample, there are notes associated with the processing 
method (delay in sample processing, storage conditions on the ward, etc.). 


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5.3.1.3 Sample Storage and Destruction 
Barcoded samples are stored in barcoded boxes in a locked freezer at either -20 or -800C according 
to stability requirements. These freezers are located onsite in the BPC and offsite at NCI Frederick 
Central Repository Services in Frederick, MD. Visitors to the laboratory are required to be 
accompanied by laboratory staff at all times.  
Access to stored clinical samples is restricted. Samples will be stored until requested by a 
researcher named on the protocol. All requests are monitored and tracked in Labmatrix. 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 the IRB approved protocol) and that any unused samples 
must be returned to the BPC. It is the responsibility of the NCI Principal Investigator to ensure that 
the samples requested are being used in a manner consistent with IRB approval. 
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.  
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. The PI will record any loss or 
unanticipated destruction of samples as a deviation. Reporting will be per the requirements of 
Section 7.2. 
Sample barcodes are linked to patient demographics and limited clinical information. This 
information will only be provided to investigators listed on this protocol, via registered use of the 
Labmatrix. It is critical that the sample remains linked to patient information such as race, age, 
dates of diagnosis and death, and histological information about the tumor, in order to correlate 
genotype with these variables.  
5.3.2 Procedures for Storage of Patient Samples in the Laboratory of Dr. Trepel 
Contact the Trepel Lab by email (Jane Trepel: trepel@helix.nih.gov; Min-Jung Lee: 
leemin@mail.nih.gov; Akira Yuno: akira.yuno@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.  
A lab member will come to pick up the blood. Please keep blood at ambient temperature. Members 
of the lab will enter the samples into a secure password protected patient’s sample tracking 
database (Translational Pharmacodynamics Research Group Patient Sample Management System) 
and process the samples.  
Sample barcodes are linked to patient demographics and limited clinical information. This 
information will only be provided to investigators listed on this protocol.  It is critical that the 
sample remains coded and linked to patient information such as race, age, dates of diagnosis and 
death, and histological information about the tumor, in order to correlate with these variables. 
Blood samples will be stored initially in the Trepel Lab in the Magnuson Clinical Center. If, at any 
time, a subject 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). When a patient withdraws consent the 


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participant’s data will be excluded from future distributions, but data that have already been 
distributed for approved research use will not be able to be retrieved. 
The PI will record any loss or unanticipated destruction of samples as a deviation. Reporting will 
be per the requirements of Section 7.2. 
5.3.3 Procedures for Storage of Tissue Specimens in the Laboratory of Pathology 
Tissues designated for clinical diagnostics are transported to the Laboratory of Pathology (LP) 
where they are examined grossly and relevant portions are fixed, embedded in paraffin and 
sectioned and stained for diagnostic interpretation. Unutilized excess tissue that is not embedded 
in paraffin is stored in formalin for up to three months, in accordance with College of American 
Pathologists/Joint Commission on Accreditation of Healthcare Organizations (CAP/JCAHO) 
guidelines, and then discarded. Following completion of the diagnostic workup, the slides and 
tissue blocks are stored indefinitely in the LP’s clinical archives. All specimens are catalogued and 
retrieved utilizing the clinical laboratory information systems, in accordance with CAP/JCAHO 
regulations. The use of any stored specimens for research purposes is only allowed when the 
appropriate IRB approval has been obtained. In some cases, this approval has been obtained via 
the original protocol on which the patient was enrolled. 
5.3.4 Procedures for Storage of Patient Samples in the Laboratory of Dr. Hernandez 
Patient samples, collected for the purpose of research under IRB approved protocols where Dr. 
Hernandez is Principal Investigator, may be archived in the Laboratory of Dr. Hernandez. All data 
associated with archived clinical research samples is entered into the NCI Labmatrix database. All 
staff in Dr. Hernandez’s laboratory have received updated NIH/CIT training and maintain 
standards of computer security. 
The data recorded for each sample includes the patient ID, trial name/protocol number, date 
drawn/collected, treatment cycle/time point, cell source (e.g. peripheral blood, marrow, biopsy) as 
well as box and freezer location. Patient demographics that correlate treatment outcomes and 
therapies with the samples can be obtained only through the NCI clinical records. All received 
samples will receive a unique bar code number, which will be added to the sample NCI Labmatrix 
database. Only this bar code will be recorded on the sample vial and the vials will not be traceable 
back to patients without authorized access to the NCI Labmatrix database. 
Samples are stored in freezers at -80°C (sera, plasma, tissue samples) or under liquid nitrogen 
(cells), according to stability requirements. These freezers are located onsite at Dr. Hernandez’s 
laboratory. Access to samples from a protocol for research purposes will be by permission of the 
Principal Investigator. 
5.3.5 Protocol Completion/Sample Destruction 
All specimens obtained in the protocol are used as defined in the protocol. Any specimens that are 
remaining at the completion of the protocol will be transferred to protocol 13C0176.  
Subjects will be co-enrolled on protocol 13C0176. Thus, all tissue will be stored, tracked and 
disposed after transfer as specified in protocol 13C0176. 


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If the patient withdraws consent the participant’s data will be excluded from future distributions, 
but data that have already been distributed for approved research use will not be able to be 
retrieved. 
The PI will record any loss or unanticipated destruction of samples as a deviation. Reporting will 
be per the requirements of Section 7.2.  
5.3.6 A Certificate of Confidentiality 
A Certificate of Confidentiality will be obtained for this study. 
5.3.7 Management of Results 
Subjects will be contacted if a clinically actionable gene variant is discovered. Clinically 
actionable findings for the purpose of this study are defined as disorders appearing in the American 
College of Medical Genetics and Genomics recommendations for the return of incidental findings 
that is current at the time of primary analysis. (A list of current guidelines is maintained on the 
CCR intranet: https://ccrod.cancer.gov/confluence/display/CCRCRO/Incidental+Findings+Lists). 
Subjects will be contacted at this time with a request to provide a blood sample to be sent to a 
CLIA certified laboratory.  
5.3.8 Genetic Counseling 
If the research findings are verified in the CLIA certified lab, the subject will be offered the 
opportunity to come to NIH (at our expense) to have genetic education and counseling with the 
NCI Genetics Branch to explain this result. If the subject does not want to come to NIH, a referral 
to a local genetic healthcare provider will be provided (at their expense).  
This is the only time during the course of the study that incidental findings will be returned. No 
interrogations regarding clinically actionable findings will be made after the primary analysis. 
6 
DATA COLLECTION AND EVALUATION  
 
DATA COLLECTION 
For the purposes of the research sample analyses and correlation with clinical outcomes, 
demographic information, histology, operative and peri-operative interventions, pathologic 
findings, laboratory and imaging parameters (performed as part of routine or protocol specified 
patient care) may be collected on this study. The PI will be responsible for overseeing entry of data 
into an in-house password protected electronic system (C3D and Labmatrix) 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.  


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Document AEs from the first study intervention, Study Day -3, through the last study intervention 
on Cycle 2 Day 15. Beyond 28 days after the last intervention, only adverse events which are 
serious and related to the study intervention need to be recorded. 
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, this will be reported expeditiously per 
requirements in Section 7.2.1.  
6.1.1 Routine Data Collection 
Following enrollment and for the duration of the study, graded adverse events will be described in 
the source documents, reviewed by the designated research nurse, and captured in C3D unless 
otherwise indicated below.  
Note: No Grade 1 adverse events will be recorded.  
6.1.1.1 Concomitant Medications (captured in source documents only)  
o Only those medications that the patient is taking at baseline on a routine basis or 
medications that cause an AE will be captured. (Thus, one time medications, PRN 
medications, and medications given to treat adverse events will not be captured.) 
6.1.1.2 Laboratory Events 
Laboratory events that will be described in the source documents and captured in C3D: 
• During hospitalization for the procedure, only the following labs will be uploaded into 
C3D:  
o Admission labs,  
o First morning labs drawn after 4:00 AM, and  
o Labs that support the diagnosis of a reportable event. 
• In the immediate post-operative period (7 days), only the following values will be 
captured (including laboratory values obtained at sites other than the NIH Clinical Center): 
o Hemoglobin, total white blood cell count, absolute neutrophil count, platelet count 
o PT, PTT, or INR 
o Creatinine, ALT, AST, total bilirubin  
Any unexpected laboratory abnormality ≥ Grade 3 AND associated with symptoms or an 
intervention will be reported. We recognize that laboratory abnormalities are the norm for 
subjects undergoing the procedures as outlined in this study and therefore will exercise PI 
discretion in reporting of abnormalities outside the reported ULN. 
6.1.1.3  Exceptions to Adverse Event Recording 
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: 


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o Results in discontinuation from the study 
o Is not directly attributable to the operation  
o Is associated with clinical signs or symptoms  
o Requires treatment or any other therapeutic intervention 
o Is associated with death or another serious adverse event, including hospitalization.  
o Is judged by the Investigator to be of significant clinical impact 
o 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. 
Non-laboratory, non-concomitant medication events that will be captured only in the source 
documents: 
• During hospitalization for surgical resection 
o ≤ Grade 3 events except unexpected events that are possibly or definitely related 
to the research. 
• Post-operative recovery period (following discharge)  
o ≤ Grade 3 events except unexpected events that are possibly or definitely related 
to the research. 
o Note: Events that result in hospitalization for convenience will not be reported. 
 
 
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:  
o Coded, linked data in an NIH-funded or approved public repository. 
o Coded, linked data in BTRIS (automatic for activities in the Clinical Center). 
o 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: 
o An NIH-funded or approved public repository, clinicaltrials.gov, dbGaP. 
o BTRIS (automatic for activities in the Clinical Center). 
o Approved outside collaborators under appropriate individual agreements. 
o Publication and/or public presentations. 
When will the data be shared? 
o Before publication. 


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o At the time of publication or shortly thereafter. 
6.2.2 Genomic Data Sharing Plan 
Unlinked genomic data will be deposited in public genomic databases such as dbGaP in 
compliance with the NIH Genomic Data Sharing Policy.  
 
RESPONSE CRITERIA 
For the purposes of this study, patients should be re-evaluated for response at C1D1, C1D8, 
C2D1 and C2D15 (+/- 48 hours) and at EOT.  
Response and progression will be evaluated in this study using the new international criteria 
proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline 
(version 1.1).[1] 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. 
6.3.1 Definitions 
Evaluable for toxicity: All patients will be evaluable for toxicity from the time of their first 
treatment with MVT-5873. 
Evaluable for Objective Response: Only those patients who have measurable disease present at 
baseline, have received at least one dose of the monoclonal antibody, undergone a resection and 
have had their disease re-evaluated will be considered evaluable for DFS response. (Note: 
Patients who exhibit objective disease progression prior to the end of Cycle 1 will also be 
considered evaluable.) 
Evaluable Non-Target Disease Response: Patients who have lesions present at baseline that are 
evaluable but do not meet the definitions of measurable disease, have received at least dose of 
the monoclonal antibody, undergone a resection 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 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:  
• By chest x-ray: >20 mm;  
• By CT scan:  
o Scan slice thickness 5 mm or under: as >10 mm 
o Scan slice thickness >5 mm: double the slice thickness  
• With calipers on clinical exam: >10 mm.   
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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. 
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 patient, 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.  
6.3.3 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. 


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Clinical lesions: Clinical lesions will only be considered measurable when they are superficial 
(e.g., skin nodules and palpable lymph nodes) and ≥10 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.  
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 


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clinical response. Specific guidelines for both CA-125 response (in recurrent ovarian cancer) and 
PSA response (in recurrent prostate cancer) have been published. [2-4]   I 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.[5]  
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). 
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. 
6.3.4 Response Criteria 
6.3.4.1 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, 
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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. 
6.3.4.2 Evaluation of Non-Target Lesions 
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 
patient 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). 
6.3.4.3 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 patient's best response assignment will 
depend on the achievement of both measurement and confirmation criteria. 
For Patients 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 


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Target 
Lesions 
Non-Target 
Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response when 
Confirmation is Required* 
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 
* 
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: 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. 
For Patients 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 


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Non-Target Lesions 
New Lesions 
Overall Response 
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 
6.3.5 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.  
6.3.6 Progression-Free Survival 
Intrahepatic PFS is defined as the duration of time from date of operation to the date of first 
observation of progressive disease within the liver or death, whichever comes first.  
Extrahepatic PFS is defined as the duration of time from date of operation to the date of first 
observation of progressive disease outside of the liver or death, whichever comes first. 
 
TOXICITY CRITERIA  
The following adverse event management guidelines are intended to ensure the safety of each 
patient while on the study.  The descriptions and grading scales found in the revised NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE 
reporting.  All appropriate treatment areas should have access to a copy of the CTCAE version 
5.0.  A copy of the CTCAE version 5.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50).  
7 
NIH REPORTING REQUIREMENTS / DATA AND SAFETY MONITORING PLAN 
 
DEFINITIONS 
Please refer to definitions provided in Policy 801: Reporting Research Events found here. 
 
OHSRP OFFICE OF COMPLIANCE AND TRAINING / IRB REPORTING  
7.2.1 Expedited Reporting 
Please refer to the reporting requirements in Policy 801: Reporting Research Events and Policy 
802 Non-Compliance Human Subjects Research found here.  


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Note: Only IND Safety Reports that meet the definition of an unanticipated problem will need to 
be reported per these policies. 
7.2.2 IRB Requirements for PI Reporting at Continuing Review 
Please refer to the reporting requirements in Policy 801: Reporting Research Events found here. 
 
NCI CLINICAL DIRECTOR REPORTING  
Problems expeditiously reported to the OHSRP in iRIS will also be reported to the NCI Clinical 
Director.  A separate submission is not necessary as reports in iRIS will be available to the 
Clinical Director. 
In addition to those reports, all deaths that occur within 28 days after receiving a research 
intervention should be reported via email to the Clinical Director unless they are due to 
progressive disease.   
To report these deaths, please send an email describing the circumstances of the death to Dr. 
Dahut at NCICCRQA@mail.nih.gov within one business day of learning of the death. 
 
NIH REQUIRED DATA AND SAFETY MONITORING PLAN 
7.4.1 Principal Investigator/Research Team  
The clinical research team will meet on a weekly basis when patients are being actively treated on 
the trial to discuss each patient. Decisions about dose level enrollment and dose escalation if 
applicable will be made based on the toxicity data from prior patients.  
All data will be collected in a timely manner and reviewed by the principal investigator or a lead 
associate investigator. Events meeting requirements for expedited reporting as described in Section 
7.2.1 will be submitted within the appropriate timelines.  
The principal investigator will review adverse event and response data on each patient 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.  
8 
SPONSOR SAFETY REPORTING 
 
DEFINITIONS 
8.1.1 Adverse Event  
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product (ICH E6 (R2)). 


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8.1.2 Serious Adverse Event (SAE) 
An adverse event or suspected adverse reaction is considered serious if in the view of the 
investigator or the sponsor, it results in any of the following: 
• 
Death, 
• 
A life-threatening adverse event (see Section 8.1.3) 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
o A hospitalization/admission that is pre-planned (i.e., elective or scheduled surgery 
arranged prior to the start of the study), a planned hospitalization for pre-existing 
condition, or a procedure required by the protocol, without a serious deterioration in 
health, is not considered a serious adverse event. 
o A hospitalization/admission that is solely driven by non-medical reasons (e.g., 
hospitalization for patient convenience) is not considered a serious adverse event.  
o Emergency room visits or stays in observation units that do not result in admission to 
the hospital would not be considered a serious adverse event. The reason for seeking 
medical care should be evaluated for meeting one of the other serious criteria. 
• 
Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect. 
• 
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 patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition. 
8.1.3 Life-threatening  
An adverse event or suspected adverse reaction is considered "life-threatening" if, in the view of 
either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an adverse event or suspected adverse reaction that, had it occurred in a 
more severe form, might have caused death. (21CFR312.32) 
8.1.4 Severity 
The severity of each Adverse Event will be assessed utilizing the CTCAE version 5.0. 
8.1.5 Relationship to Study Product 
All AEs will have their relationship to study product assessed using the terms:  related or not 
related.   
• Related – There is a reasonable possibility that the study product caused the adverse 
event. Reasonable possibility means that there is evidence to suggest a causal relationship 
between the study product and the adverse event. 


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• Not Related – There is not a reasonable possibility that the administration of the study 
product caused the event. 
 
ASSESSMENT OF SAFETY EVENTS 
AE information collected will include event description, date of onset, assessment of severity 
and relationship to study product and alternate etiology (if not related to study product), date of 
resolution of the event, seriousness and outcome. The assessment of severity and relationship to 
the study product will be done only by those with the training and authority to make a diagnosis 
and listed on the Form FDA 1572 as the site principal investigator or sub-investigator.  AEs 
occurring during the collection and reporting period will be documented appropriately regardless 
of relationship.  AEs will be followed through resolution. 
SAEs will be: 
• 
Assessed for severity and relationship to study product and alternate etiology (if not 
related to study product) by a licensed study physician listed on the Form FDA 1572 as 
the site principal investigator or sub-investigator. 
• 
Recorded on the appropriate SAE report form, the medical record and captured in the 
clinical database. 
• 
Followed through resolution by a licensed study physician listed on the Form FDA 1572 
as the site principal investigator or sub-investigator. 
For timeframe of recording adverse events, please refer to Section 6.1.  
 
REPORTING OF SERIOUS ADVERSE EVENTS 
Any AE that meets protocol-defined serious criteria or meets the definition of Adverse Event of 
Special Interest that require expedited reporting must be submitted immediately (within 24 hours 
of awareness) to OSRO Safety using the CCR SAE report form. 
All SAE reporting must include the elements described in Section 8.2. 
SAE reports will be submitted to the Center for Cancer Research (CCR) at: 
OSROSafety@mail.nih.gov and to the CCR PI and study coordinator.  CCR SAE report form 
and instructions can be found at: 
https://ccrod.cancer.gov/confluence/pages/viewpage.action?pageId=157942842  
Following the assessment of the SAE by OSRO, other supporting documentation of the event 
may be requested by the OSRO Safety and should be provided as soon as possible. 
 
REPORTING PREGNANCY  
8.4.1 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 no later than 24 hours of 


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when the Investigator becomes aware of it. The Investigator should notify the Sponsor no later 
than 24 hours of when the outcome of the Pregnancy become known, 
Pregnancy itself is not regarded as an SAE. However, congenital abnormalities or birth defects 
and spontaneous miscarriages that meet serious criteria (Section 8.1.2) should be reported as 
SAEs.  
The outcome of all pregnancies (spontaneous miscarriage, elective termination, ectopic 
pregnancy, normal birth, or congenital abnormality) should be followed up and documented. 
8.4.2 Paternal Exposure 
Male patients should refrain from fathering a child or donating sperm during the study and for 90 
days after the last dose of MVT-5873. 
Pregnancy of the patient’s partner is not considered to be an AE. However, the outcome of all 
pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal birth, or 
congenital abnormality) occurring from the date of the first dose until 90 days after the last dose 
should, if possible, be followed up and documented. 
 
REGULATORY REPORTING FOR STUDIES CONDUCTED UNDER CCR-SPONSORED IND 
Following notification from the investigator, CCR, the IND sponsor, will report any suspected 
adverse reaction that is both serious and unexpected.  CCR will report an AE as a suspected 
adverse reaction only if there is evidence to suggest a causal relationship between the study 
product and the adverse event.  CCR will notify FDA and all participating investigators (i.e., all 
investigators to whom the sponsor is providing drug under its INDs or under any investigator’s 
IND) in an IND safety report of potential serious risks from clinical trials or any other source, as 
soon as possible, in accordance to 21 CFR Part 312.32.  
All serious events will be reported to the FDA at least annually in a summary format. 
9 
CLINICAL MONITORING  
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 and secondary study endpoints; adherence to the protocol, 
regulations, ICH E6, and SOPs; and human subjects protection. This is done through 
independent verification of study data with source documentation focusing on: 
• Informed consent process 
• Eligibility confirmation 
• Drug administration and accountability 
• Adverse events monitoring 
• Response assessment. 
The monitoring program also extends to multi-site research when the CCR is the coordinating 
center. 


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This trial will be monitored by personnel employed by a CCR 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.   
10 STATISTICAL CONSIDERATIONS 
 STATISTICAL HYPOTHESES  
10.1.1 Primary Efficacy Endpoints 
The primary objectives of this trial are to: 
1) Determine if the use of the monoclonal antibody in the immediate perioperative period is 
safe for subjects undergoing the two main procedures: hepatic resection and pancreatic 
resection. 
2) Determine whether subjects with pancreatic cancer, cholangiocarcinoma, or colorectal 
cancer metastatic to the liver who undergo a resection and receive the anti-CA  
19-9 monoclonal antibody can decrease their 12-month recurrence probability from 50% to 
25% for pancreatic cancer, from 40% to 20% for colorectal cancer, and from 40% to 20% 
for cholangiocarcinoma. 
10.1.2 Secondary Efficacy Endpoints 
The secondary end-point of disease-free survival, defined as the time of resection (D0) until the 
time of documented clinical recurrence (radiographically or pathologically) will be determined for 
each patient on study. In the absence of a knowable time of recurrence, time of death will be used 
as a surrogate. The data will be compared to data obtained from recent randomized clinical trials 
with adjuvant therapy, and each cohort will be analyzed separately. We anticipate maturation of 
this data will take years to complete, and plan an analysis at 3 years from the time of accrual of 
the last patient in each cohort.  
 SAMPLE SIZE DETERMINATION: 
Sample sizes are calculated on the basis of 12-month recurrence probability for each of the three 
histologies accrued in this study (pancreatic cancer, cholangiocarcinoma and colorectal cancer): 
1. Pancreatic cancer: Data from ESPAC4 indicate that the expected 12-month recurrence 
probability is ~50%. The goal is to determine if use of the monoclonal antibody will be 
potentially associated with a decrease to a 25% recurrence probability, 12 months after 
surgery. As a means of determining the sample size for the study, with 23 evaluable 
subjects with pancreatic cancer who receive surgery and the monoclonal antibody and are 
potentially followed for 12 months, there would be 80% power to rule out a 50% recurrence 
rate in favor of a 25% recurrence rate, with a one-sided 0.10 significance level exact 
binomial test. In practice, if 23 subjects are treated and if 8/23 (34.8%) have recurred by 
one year, then the upper one-sided 90% confidence bound on 8/23 is 50.3%, which would 
indicate a marginally improved recurrence probability compared to a historical 50%. In 
addition, the lower one-sided 90% confidence bound on 8/23 is 21.4%, which demonstrates 
that 8/23 could be shown to be consistent with as low as a 25% recurrence rate. In practice, 


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confidence intervals about the recurrence probabilities will be reported, but no formal 
hypothesis test will be undertaken. 
2. Cholangiocarcinoma: Data from the BILCAP trial and single institution series indicate 
that the expected 12-month recurrence probability is 40%. The goal is to determine if use 
of the monoclonal antibody will be potentially associated with a decrease to a 20% 
recurrence probability, 12 months after surgery. As a means of determining the sample size 
for the study, with 24 evaluable subjects with cholangiocarcinoma who receive surgery and 
the monoclonal antibody, and are potentially followed for 12 months, there would be 81% 
power to rule out a 40% recurrence rate in favor of a 20% recurrence rate, with a one-sided 
0.10 significance level exact binomial test. In practice, if 24 subjects are treated and if 6/24 
(25%) have recurred by one year, then the upper one-sided 90% confidence bound on 6/24 
is 39.8%, which would indicate a marginally improved recurrence probability compared to 
a historical 40%. In addition, the lower one-sided 90% confidence bound on 6/24 is 13.7%, 
which demonstrates that 6/24 could be shown to be consistent with a 20% recurrence rate. 
In practice, confidence intervals about the recurrence probabilities will be reported, but no 
formal hypothesis test will be undertaken. 
3. Colorectal cancer: Data from MSKCC indicate that the expected 12-month recurrence 
probability is 40%. The goal is to determine if use of the monoclonal antibody will be 
potentially associated with a decrease to a 20% recurrence probability, 12 months after 
surgery. As a means of determining the sample size for the study, with 24 evaluable 
subjects with colorectal cancer who receive surgery and the monoclonal antibody, and are 
potentially followed for 12 months, there would be 81% power to rule out a 40% recurrence 
rate in favor of a 20% recurrence rate, with a one-sided 0.10 significance level exact 
binomial test. In practice, if 24 subjects are treated and if 6/24 (25%) have recurred by one 
year, then the upper one-sided 90% confidence bound on 6/24 is 39.8%, which would 
indicate a marginally improved recurrence probability compared to a historical 40%. In 
addition, the lower one-sided 90% confidence bound on 6/24 is 13.7%, which demonstrates 
that 6/24 could be shown to be consistent with a 20% recurrence rate. In practice, 
confidence intervals about the recurrence probabilities will be reported, but no formal 
hypothesis test will be undertaken. 
This study contains the stratified accrual of two successive safety lead-in cohorts, there is the 
potential for up to 24 safety lead-in subjects to be enrolled. In addition, 71 (23+24+24) subjects 
will be enrolled in the expansion cohorts. As safety lean-in subjects treated at the MTD may be 
evaluated in the expansion cohorts, 83 (24-12+71) evaluable subjects will be required. It is 
expected that approximately 24-30 subjects per year may enroll onto the study, with approximately 
8-10 subjects per year for each of the three histologies. Thus, it is expected that 3-4 years may be 
required to enroll up to 83 total evaluable subjects. To allow for unevaluable subjects and screening 
failures, the total accrual ceiling for the trial will be set at 105 subjects. 
 POPULATIONS FOR ANALYSIS 
Modified intention to treat: all subjects who receive at least one dose of the monoclonal antibody 
and undergo a resection will be included in the statistical analyses performed. 


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10.3.1 Evaluable for Toxicity  
All patients will be evaluable for toxicity from the time of their first treatment with MVT-5873. 
10.3.2 Evaluable for Objective Response  
Only those patients who have measurable disease present at baseline, have received at least one 
dose of the monoclonal antibody, undergone a resection and have had their disease re-evaluated 
will be considered evaluable for response. CA 19-9 will be measured for response. (Note: Patients 
who exhibit objective disease progression prior to the end of Cycle 1 will also be considered 
evaluable.) 
10.3.3 Evaluable Non-Target Disease Response 
Patients who have lesions present at baseline that are evaluable but do not meet the definitions of 
measurable disease, have received at least dose of the monoclonal antibody, undergone a resection 
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.  
 STATISTICAL ANALYSES 
10.4.1 General Approach 
Fractions of subjects who recur by 12 months will be reported along with appropriate confidence 
intervals. Estimates of the fraction experiencing important side effects will be reported along with 
appropriate confidence intervals. 
10.4.2 Analysis of the Primary Efficacy Endpoints 
1. Safety: see Section 10.4.4. 
2. Recurrence-free survival at 12 months: see Section 10.4.1. 
10.4.3 Analysis of the Secondary Efficacy Endpoints 
Disease Free survival (DFS) is the time from resection to the time of definitive evidence 
recurrence, defined radiographically or by biopsy  
DFS will be determined using the Kaplan-Meier method, along with 80% and 95% two-side 
confidence intervals at the 12-month time point as well as the median for each of the three 
histologies. Safety will be evaluated as stated in the next section. 
10.4.4 Safety Analyses 
AE’s will be captured with the first dose of MVT-5873 and continue until 28 days after the last 
dose of MVT 5873, or the start of additional therapy, whichever comes first. 
The primary outcome measure (1 of 2) for this trial is safety of immediate peri-operative  
MVT-5873. For these reasons, we have stratified accrual based on two successive safety lead-in 
cohorts, and predicated successive accrual to successful completion of the preceding cohort. For 
example, if we are unsuccessful accruing subjects to lead-in Cohort 2, the remainder of accrual 
will only take place with subjects meeting study inclusion criteria and safety lead-in Cohort 1 
criteria. As described in Section 3, the safety lead-in cohorts have been designed as an extra safe 


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guard to ensure patient safety by accruing subjects with the least amount of transaminase and 
bilirubin abnormalities first.  
However, we also want to ensure that the use of MVT-5873 is not associated with an increase in 
procedure related complications. For this reason, we have added additional safe guards, which are 
procedure-related and irrespective of histology:  
1. For Subjects Undergoing a Liver Resection: 
The fraction of subjects whose treatment results in hepatic insufficiency will be noted and 
reported along with two-sided 80% and 95% confidence intervals. The general expectation 
is that up to 10% of subjects undergoing a hepatic resection will experience hepatic 
insufficiency.  
If after the first 10 evaluable subjects who receive this procedure, there are 3 or more who 
experience hepatic insufficiency, this will be considered excessive since the one-sided 
lower 90% confidence interval bound on 3/10 is 11.6%, which would demonstrate potential 
inconsistency with 10%. T, the fraction of subjects who experience hepatic insufficiency 
(AST and/or ALT elevation in combination with ascites or altered mental status) will be 
reported, along with a 95% two-sided confidence interval. In addition, each patient will 
have slides made from the resected tissue and if a single patient within a cohort is noted to 
have significant necrosis and/or direct damage to the biliary tree, then no further subjects 
will be enrolled onto that cohort.  
2. For Subjects Undergoing a Pancreas Resection: 
For subjects who undergo a pancreatic resection, the fraction of subjects whose treatment 
results in pancreatic leaks will be noted and reported along with two-sided 80% and 95% 
confidence intervals. The general expectation is that up to 20% of subjects undergoing a 
pancreatic resection will end up with a leak.  
If after the first 10 evaluable subjects who receive this procedure, there are 5 or more who 
experience a leak, this will be considered excessive since the one-sided lower 90% 
confidence interval bound on 5/10 is 26.7%, which would demonstrate potential 
inconsistency with 20%. 
10.4.5 Baseline Descriptive Statistics 
Demographic and baseline clinical characteristics of all subjects will be reported. 
10.4.6 Planned Interim Analyses 
For the two types of procedures, determination of whether there are excessive side effects after 
treatment of 10 evaluable subjects receive each type of procedure will take place, as described in 
the section above.  
10.4.7 Exploratory Analyses 
The following objectives will be analyzed as indicated for each: 


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The Kaplan-Meier method will be used to determine OS by disease type for subjects treated with 
preoperative MVT-5873. 
For patients that experience a rise in AST, ALT or Bilirubin prior to surgery, the mechanism(s) of 
liver function test abnormalities associated with MVT-5873 administration will be determined by 
having liver tissue evaluated with a battery of immunohistochemical stains at the discretion of the 
liver pathologist, Dr. David Kleiner.  
In order to determine the tumor penetration of MVT-5873 in primary tumors of the pancreas and 
bile ducts, and in metastatic colorectal cancers to the liver, antibody staining (using an antibody 
against MVT-5873) will be performed by the Hernandez Laboratory on each tumor sample 
removed. The samples will be scored for staining positivity.   
Evaluation of CTCs obtained before receiving the monoclonal antibody and just prior to surgery 
will be undertaken in order to determine the impact of MVT-5873 therapy on circulating tumor 
cells. The difference in the CTC levels between the time points will be determined and tested for 
significance by a Wilcoxon signed rank test. If multiple statistical tests of these laboratory-based 
parameters are performed, the results will be reported without any formal correction for multiple 
comparisons.   
Resected tumor-bearing liver and pancreas will be perfused in order to develop ex vivo models for 
pancreatic cancer, cholangiocarcinoma, and metastatic colorectal cancer. A model will be deemed 
viable if the tissue remains intact and functional for 48 hours and if the transcriptome of the tumor 
changes less than 10% from baseline during the perfusion.  
Ex vivo analysis of peritoneal tumor tissue with resected mesothelial metastases will be performed 
utilizing the SMART System to support the identification of underpinnings of interventional 
chemotherapeutic and immunomodulatory agent effects in subjects after undergoing pre-operative 
MVT-5873 therapy. 
11 COLLABORATIVE AGREEMENTS  
 MATERIAL TRANSFER AGREEMENT (MTA) 
There are MTAs in place with the following, see Section 5.2 for additional information on the 
information/materials being shared with each: 
• Genomic Expression (43208-17). 
• Zamboni Laboratory – University of North Carolina at Chapel Hill (pending) 
12 HUMAN SUBJECTS PROTECTIONS  
 RATIONALE FOR SUBJECT SELECTION 
Subjects with a diagnosis of colorectal cancer with predominantly hepatic metastases will be 
eligible for this study, as will subjects with resectable pancreatic cancer and cholangiocarcinoma. 
Eligibility assessment will be made solely on the patient’s medical status. Recruitment of subjects 
on this study will be through standard CCR mechanisms. The investigational nature and objectives 
of this trial, the procedure and the treatments involved, the attendant risks and discomforts, 
potential benefits and potential alternative therapies will be carefully explained to the subjects in 


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the clinic setting and in the hospital prior to treatment and prior to obtaining a signed informed 
consent. 
 PARTICIPATION OF CHILDREN 
Children are excluded from this study because no dosing or adverse event data are currently 
available on the use of MVT-5873 in subjects < 18 years of age. Since the efficacy of this 
experimental procedure is unknown, it does not seem reasonable to expose children to this risk 
without further evidence of benefit. Should results of this study indicate efficacy, which is not 
responsive to other standard forms of therapy, future research can be conducted in the pediatric 
population to evaluate potential benefit in that patient population. 
 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 12.4), 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 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. 
 EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS 
The potential benefit is increased likelihood of cure from complete tumor extirpation. Therefore, 
although this protocol involves greater than minimal risk, it presents the prospect of direct benefit 
to individual subjects. The major risk is that the use of peri-operative MVT-5873 may increase the 
likelihood of procedure related complications, although we believe this risk to be small. 
Risks and benefits will be carefully discussed with the patient at the time consent is obtained. 
Patients will be monitored throughout the study in order to limit the consequences of any adverse 
events. 
The risks and benefits of participation for adults who become unable to consent on study are no 
different than those described for the rest of the study population. 
12.4.1 Risks 
12.4.1.1 Abdominal Surgery 
The risks for this protocol include the risks associated with any abdominal surgery. This includes 
postoperative bleeding, intra-abdominal infection, wound healing complications including fascial 
dehiscence, enterocutaneous fistulas, anesthetic mishap and perioperative death. All attempts will 


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be made to avoid unnecessary enterotomies or a bowel resection where feasible. In the case of 
intra-abdominal catastrophe after surgery, subjects may require reoperation.  
12.4.1.2 Study Drug Risks 
The use of peri-operative MVT-5873 may increase the likelihood of procedure related 
complications, although this risk is believed to be small. 
12.4.1.3 Blood Sampling 
Side effects of blood draws include pain and bruising, lightheadedness, and rarely, fainting.  
12.4.1.4 Urine Collection 
There is no physical risk involved with urine collection. 
12.4.1.5 Tissue Collection Risks   
All care will be taken to minimize risks that may be incurred by tumor sampling. However, there 
are procedure-related risks (such as bleeding, infection and visceral injury) that will be explained 
fully during informed consent. If subjects suffer any physical injury as a result of the biopsies, 
immediate medical treatment is available at the NCI’s Clinical Center in Bethesda, MD. Although 
no compensation is available, any injury will be fully evaluated and treated in keeping with the 
benefits or care to which subjects are entitled under applicable regulations. 
Biopsy side effects may include a mild burning sensation when the numbing medicine is injected 
into the skin, small amounts of bleeding at the biopsy site, and rarely, a small infection at the site. 
Biopsy sites usually heal very well and with very little scarring. 
12.4.1.6 Electrocardiogram (EKG) 
This test is safe and side effects are unlikely, but it may be uncomfortable when the electrodes are 
taken off after the test is completed.  
12.4.1.7 Scans and Contrast  
The most common discomfort is the length of time a patient must lay still during a scan. Patients 
may also become uncomfortable with the closed space of the machines. 
There is a small risk of reaction in scans involving contrast (including gadolinium). Common 
reactions include pain in the vein where the contrast was given, a metallic or bitter taste in the 
mouth, headache, nausea and a warm or flushing feeling that lasts from 1-3 minutes. In very rare 
cases, severe reactions that affect breathing, heart rhythm or blood pressure have occurred. 
Gadolinium for research MRI scans will not be given to patients who have impaired kidney 
function or who received gadolinium within the previous month.  
An IV line may need to be inserted for administration of the contrast agent or anesthetic, which 
may cause pain at the site where the IV is placed and there is a small risk of bruising or infection. 
12.4.2 Risks of Exposure to Ionizing Radiation  
This research study involves exposure to radiation from CT scans, collected for research purposes 
only. Subjects will be exposed to approximately 8.5 rem. This amount of radiation is above the 


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guideline of 5 rem per year, and will expose the subject to the roughly the same amount of radiation 
as 28.3 years of background radiation. 
12.4.3 Non-Physical Risks of Genetic Research 
12.4.3.1 Risk of Receiving Unwanted Information 
Anxiety and stress may arise as a result of the anticipation that unwanted information regarding 
disease related DNA sequencing or disease tendencies, or misattributed paternity. Subjects will be 
clearly informed that the data related to DNA sequencing and genetic analysis is coded, 
investigational and will not be shared with subjects, family members or health care providers. 
12.4.3.2 Risk Related to Possibility that Information May be Released 
This includes the risk that data related to genotype, DNA sequencing or risk for disease tendency 
or trait can be released to members of the public, insurers, employers, or law enforcement 
agencies. Although there are no plans to release results to the subjects, family members or health 
care providers, this risk will be included in the informed consent document.  
12.4.3.3 Risk to Family or Relatives 
Family members or relatives may or may not want to be aware of familial tendencies or genetic 
risks of disease which may cause anxiety about possible future health problems.  
12.4.4 Benefits 
The potential benefit to subjects undergoing this therapy would be cure, or palliation at a minimum, 
in terms of preventing or delaying intra-abdominal tumor recurrence and metastases elsewhere 
which can be a devastating and painful source of symptoms and cause for demise.  
12.4.5 Certificate of Confidentiality 
As part of study efforts to provide confidentiality of subject information, this study has obtained a 
Certificate of Confidentiality which helps to prevent forced disclosure of personally identifiable 
research information. The Certificate of Confidentiality allows investigators on this trial to refuse 
to disclose identifying information related to the research participants, should such disclosure have 
adverse consequences for subjects or damage their financial standing, employability, insurability 
or reputation. The informed consent includes the appropriate coverage and restrictions of the 
Certificate of Confidentiality 
 CONSENT PROCESS AND DOCUMENTATION 
The informed consent document will be provided to the participant or consent designee(s) (e.g., 
the legally authorized representative [LAR] if participant is an adult unable to consent) for 
review prior to consenting.  A designated study investigator will carefully explain the procedures 
and tests involved in this study, and the associated risks, discomforts and benefits. In order to 
minimize potential coercion, as much time as is needed to review the document will be given, 
including an opportunity to discuss it with friends, family members and/or other advisors, and to 
ask questions of any designated study investigator. A signed informed consent document will be 
obtained prior to entry onto the study. 


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The initial consent process as well as re-consent, when required, may take place in person or 
remotely (e.g., via telephone or other NIH approved remote platforms) per discretion of the 
designated study investigator and with the agreement of the participant/consent designee(s).  
Whether in person or remote, the privacy of the subject will be maintained. Consenting 
investigators (and participant/consent designee, when in person) will be located in a private area 
(e.g., clinic consult room). When consent is conducted remotely, the participant/consent designee 
will be informed of the private nature of the discussion and will be encouraged to relocate to a 
more private setting if needed.   
12.5.1 Request for Waiver of Consent for Screening Activities 
Prior to the subject signing the consent for this study pre-screening activities listed in Section 
2.2.1 may be performed.  
We request a waiver of consent for these activities as they involve only minimal risk to the 
subjects.  A waiver will not adversely affect the rights and welfare of the subjects given that the 
activities are only intended to determine suitability for screening for participation in research 
protocols.  These activities could not practicably be carried out without the wavier as central 
recruiting services, utilized in the NIH Clinical Center, perform pre-screening activities for 
multiple studies and obtaining consent for each one is beyond their resources.  The subjects will 
be provided with additional pertinent information after participation as they will be informed 
whether or not they are eligible to sign a consent for additional screening. 
 
13 PHARMACEUTICAL AND INVESTIGATIONAL DEVICE INFORMATION   
 DRUG MVT-5873 (IND # 144112) 
13.1.1 Source  
MVT-5873, also known as HuMab-5B1, is a monoclonal human IgG1 lambda antibody targeted 
against sLea. MVT-5873 is human derived and has a fully human sequence. MVT-5873 has been 
shown to bind with high affinity and specificity to sLea using in vitro cell-based assays, ELISA, 
and by glycan microarray analysis. MVT-5873 drug is manufactured by AAIPharma  
13.1.2 Toxicity  
Based on early clinical data, MVT-5873 appears to demonstrate dose limiting toxicity manifest as 
increases in liver transaminases and blood bilirubin. When seen, liver toxicity generally occurs 
early (within a few days of drug administration) and appears to be reversible.  
As with other protein based therapeutics, subjects are at risk for infusion reactions during or shortly 
after completion of an infusion of MVT-5873. The reactions are consistent with infusion reactions 
reported for other intravenous protein therapeutics and may consist of skin reactions (e.g., urticaria, 
pruritus, flushing), fever, chills, shortness of breath, and tachycardia. Reactions appear to respond 
to interruption of the infusion and administration of steroids. In many cases, following resolution 
of the infusion reactions, infusions may be restated at a lower infusion rate without return of 
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Other side effects related to MVT-5873 are mostly low grade (Grade 1 or 2) and are predominately 
GI in nature (e.g., constipation, diarrhea, nausea, vomiting), or appear consistent with systemic 
immune activation (e.g., fever, fatigue, malaise, rash). 
13.1.3 Formulation and Preparation  
MVT-5873 injection drug product contains 10 mg/mL MVT-5873 as the active ingredient. Each 
vial contains 3.1 mL of MVT-5873 drug product formulated as a solution for intravenous (IV) 
delivery. The table below provides a complete list of ingredients and quantitative formulation on 
a per mL basis. 
Ingredient 
Function 
Unit Formula 
Quality Standard 
MVT-5873 
Active Ingredient 
10.0 mg/mL 
NA 
L-histidine 
Buffer 
3.88 mg/mL 
USP/NF 
Hydrochloric Acid 
Buffer Modifier[1] 
Q.S. to pH 6.0 
USP/NF 
Sucrose 
Stabilizer 
3.21 mg/mL 
USP/NF 
Sodium Chloride 
Tonicity Modifier 
51.35 mg/mL 
USP/NF 
Polysorbate 80 
Solubilizer 
0.2 mg/mL 
USP/NF 
Water for Injection 
Solvent 
Q.S. to 1.0 mL 
USP 
[1] HCl may be added to the formulation buffer to attain the desired pH 
 
13.1.4 Stability and Storage  
MVT-5873 Injection drug product is packaged in clear USP Type I borosilicate glass vials  
with 20 mm West 4432/5- stoppers (grey colored coated closures) and 20 mm flip-off seals. MVT-
5873 Injection drug product is stored at -20oC. 
13.1.5 Administration Procedures 
MVT-5873 Injection drug product is provided in clear borosilicate glass vials which contain a 
sterile solution of 10 mg/mL MVT-5873, 25 mM L-histidine, 55mM sodium chloride, 150 mM 
sucrose, 0.02% Polysorbate 80, pH 6.0 in a total volume of 3.1 mL and stored at -20oC. Details of 
the method of administration are included in the Clinical Protocol and the Study Procedure Manual 
for each study. 
13.1.6 Incompatibilities   
MVT-5873 should not be administered to subjects with a history of anaphylactic reaction to human 
or humanized antibody, or to subjects with known hypersensitivity to any of its components or 
excipients. 


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14 REFERENCES  
1. 
D'Angelica, M., et al., Effect on outcome of recurrence patterns after hepatectomy for 
colorectal metastases. Ann Surg Oncol, 2011. 18(4): p. 1096-103. 
2. 
Doussot, A., et al., Recurrence Patterns and Disease-Free Survival after Resection of 
Intrahepatic Cholangiocarcinoma: Preoperative and Postoperative Prognostic Models. J 
Am Coll Surg, 2016. 223(3): p. 493-505 e2. 
3. 
Neoptolemos, J.P., et al., Comparison of adjuvant gemcitabine and capecitabine with 
gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a 
multicentre, open-label, randomised, phase 3 trial. Lancet, 2017. 389(10073): p. 1011-
1024. 
4. 
Rachman-Tzemah, C., et al., Blocking Surgically Induced Lysyl Oxidase Activity Reduces 
the Risk of Lung Metastases. Cell Rep, 2017. 19(4): p. 774-784. 
5. 
Arnoletti, J.P., et al., Portal Venous Blood Circulation Supports Immunosuppressive 
Environment and Pancreatic Cancer Circulating Tumor Cell Activation. Pancreas, 2017. 
46(1): p. 116-123. 
6. 
Al Ustwani, O., et al., Detection of circulating tumor cells in cancers of biliary origin. J 
Gastrointest Oncol, 2012. 3(2): p. 97-104. 
7. 
Court, C.M., et al., Circulating Tumor Cells Predict Occult Metastatic Disease and 
Prognosis in Pancreatic Cancer. Ann Surg Oncol, 2018. 25(4): p. 1000-1008. 
8. 
Tan, Y. and H. Wu, The significant prognostic value of circulating tumor cells in colorectal 
cancer: A systematic review and meta-analysis. Curr Probl Cancer, 2018. 42(1): p. 95-106. 
9. 
Magnani, J.L., et al., A monoclonal antibody-defined antigen associated with 
gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II. J 
Biol Chem, 1982. 257(23): p. 14365-9. 
10. 
Magnani, J.L., et al., Identification of the gastrointestinal and pancreatic cancer-
associated antigen detected by monoclonal antibody 19-9 in the sera of patients as a mucin. 
Cancer Res, 1983. 43(11): p. 5489-92. 
11. 
Ringel, J. and M. Lohr, The MUC gene family: their role in diagnosis and early detection 
of pancreatic cancer. Mol Cancer, 2003. 2: p. 9. 
12. 
Kannagi, R., Carbohydrate antigen sialyl Lewis a--its pathophysiological significance and 
induction mechanism in cancer progression. Chang Gung Med J, 2007. 30(3): p. 189-209. 
13. 
Sato, M., et al., The association of sialyl Lewis(a) antigen with the metastatic potential of 
human colon cancer cells. Anticancer Res, 1997. 17(5A): p. 3505-11. 
14. 
Feizi, T., Demonstration by monoclonal antibodies that carbohydrate structures of 
glycoproteins and glycolipids are onco-developmental antigens. Nature, 1985. 314(6006): 
p. 53-7. 


Abbreviated Title: Perioperative MVT-5873 
Version Date: 08/10/2020 
 
92 
 
15. 
Loy, T.S., et al., Distribution of CA 19-9 in adenocarcinomas and transitional cell 
carcinomas. An immunohistochemical study of 527 cases. Am J Clin Pathol, 1993. 99(6): 
p. 726-8. 
16. 
Passerini, R., et al., The pitfalls of CA19-9: routine testing and comparison of two 
automated immunoassays in a reference oncology center. Am J Clin Pathol, 2012. 138(2): 
p. 281-7. 
17. 
Ballehaninna, U.K. and R.S. Chamberlain, The clinical utility of serum CA 19-9 in the 
diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based 
appraisal. J Gastrointest Oncol, 2012. 3(2): p. 105-19. 
18. 
Dong, Q., et al., Elevated serum CA19-9 level is a promising predictor for poor prognosis 
in patients with resectable pancreatic ductal adenocarcinoma: a pilot study. World J Surg 
Oncol, 2014. 12: p. 171. 
19. 
Locker, G.Y., et al., ASCO 2006 update of recommendations for the use of tumor markers 
in gastrointestinal cancer. J Clin Oncol, 2006. 24(33): p. 5313-27. 
20. 
Nakayama, T., et al., Expression of sialyl Lewis(a) as a new prognostic factor for patients 
with advanced colorectal carcinoma. Cancer, 1995. 75(8): p. 2051-6. 
21. 
Ben-David, T., et al., The involvement of the sLe-a selectin ligand in the extravasation of 
human colorectal carcinoma cells. Immunol Lett, 2008. 116(2): p. 218-24. 
22. 
Matsui, T., et al., Sialyl Lewisa expression as a predictor of the prognosis of colon 
carcinoma patients in a prospective randomized clinical trial. Jpn J Clin Oncol, 2004. 
34(10): p. 588-93. 
23. 
Kishimoto, T., et al., Phenotypes correlating to metastatic properties of pancreas 
adenocarcinoma in vivo: the importance of surface sialyl Lewis(a) antigen. Int J Cancer, 
1996. 69(4): p. 290-4. 
24. 
Berger, A.C., et al., Undetectable preoperative levels of serum CA 19-9 correlate with 
improved survival for patients with resectable pancreatic adenocarcinoma. Ann Surg 
Oncol, 2004. 11(7): p. 644-9. 
25. 
Von Hoff, D.D., et al., Gemcitabine plus nab-paclitaxel is an active regimen in patients 
with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol, 2011. 29(34): p. 4548-
54. 
26. 
Yang, G.Y., et al., Change in CA 19-9 levels after chemoradiotherapy predicts survival in 
patients with locally advanced unresectable pancreatic cancer. J Gastrointest Oncol, 2013. 
4(4): p. 361-9. 
27. 
Koprowski, H., et al., Colorectal carcinoma antigens detected by hybridoma antibodies. 
Somatic Cell Genet, 1979. 5(6): p. 957-71. 
28. 
Kim, J.E., et al., Clinical usefulness of carbohydrate antigen 19-9 as a screening test for 
pancreatic cancer in an asymptomatic population. J Gastroenterol Hepatol, 2004. 19(2): p. 
182-6. 


Abbreviated Title: Perioperative MVT-5873 
Version Date: 08/10/2020 
 
93 
 
29. 
Morris-Stiff, G. and M.A. Taylor, Ca19-9 and pancreatic cancer: Is it really that good? J 
Gastrointest Oncol, 2012. 3(2): p. 88-9. 
30. 
Zubarik, R., et al., Screening for pancreatic cancer in a high-risk population with serum 
CA 19-9 and targeted EUS: a feasibility study. Gastrointest Endosc, 2011. 74(1): p. 87-95. 
31. 
Ragupathi, G., et al., Synthesis of sialyl Lewis(a) (sLe (a), CA19-9) and construction of an 
immunogenic sLe(a) vaccine. Cancer Immunol Immunother, 2009. 58(9): p. 1397-405. 
32. 
Sawada, R., et al., Human monoclonal antibodies to sialyl-Lewis (CA19.9) with potent 
CDC, ADCC, and antitumor activity. Clin Cancer Res, 2011. 17(5): p. 1024-32. 
33. 
Kannagi, R., et al., Quantitative and qualitative characterization of human cancer-
associated serum glycoprotein antigens expressing epitopes consisting of sialyl or sialyl-
fucosyl type 1 chain. Cancer Res, 1988. 48(13): p. 3856-63. 
34. 
Ugorski, M. and A. Laskowska, Sialyl Lewis(a): a tumor-associated carbohydrate antigen 
involved in adhesion and metastatic potential of cancer cells. Acta Biochim Pol, 2002. 
49(2): p. 303-11. 
35. 
Ohshio, G., et al., Immunohistochemical distribution of CA19-9 in normal and tumor 
tissues of the kidney. Urol Int, 1990. 45(1): p. 1-3. 
36. 
Terracciano, D., et al., Analysis of glycoproteins in human colon cancers, normal tissues 
and in human colon carcinoma cells reactive with monoclonal antibody NCL-19-9. Oncol 
Rep, 2005. 14(3): p. 719-22. 
37. 
Arends, J.W., et al., Distribution of monoclonal antibody-defined monosialoganglioside in 
normal and cancerous human tissues: an immunoperoxidase study. Hybridoma, 1983. 
2(2): p. 219-29. 
 


Abbreviated Title: Perioperative MVT-5873 
Version Date: 08/10/2020 
 
94 
 
15 APPENDICES 
 APPENDIX A: PERFORMANCE STATUS CRITERIA 
ECOG Performance Status Scale 
Grade 
Descriptions 
0 
Normal activity.  Fully active, able to carry 
on all pre-disease performance without 
restriction. 
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). 
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. 
3 
In bed >50% of the time.  Capable of only 
limited self-care, confined to bed or chair 
more than 50% of waking hours. 
4 
100% bedridden.  Completely disabled.  
Cannot carry on any self-care.  Totally 
confined to bed or chair. 
5 
Dead. 
 


MVTH 1 
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 APPENDIX B: TOXICITY TABLES 
 
Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
System Organ 
Class 
Preferred 
Term 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood 
and 
lymphatic 
system 
disorders 
1  
 
 
 
 
 
 
 
 
1 
1  
 
 
 
 
 
 
 
 
 
 
 
 
2 1  
 
 
1 
4 1  
 
 
2  
 
 
Anaemia 
1  
 
 
 
 
 
 
 
 
1 
1  
 
 
 
 
 
 
 
 
 
 
 
 
2 1  
 
 
1 
3  
 
 
 
2  
 
 
Neutropenia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
Thrombocyto
penia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
Cardiac 
disorders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 1  
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Atrial 
fibrillation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sinus 
tachycardia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Tachycardia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ear 
and 
labyrinth 
disorders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 1  
 
 
 
 
 
 
 
 
 
 
 
 
Ear 
congestion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Ear 
discomfort 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Vertigo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
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96 
 
Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
Endocrine 
disorders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypothyroidi
sm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eye disorders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
1  
 
 
 
1 
 
 
 
 
 
 
 
 
 
Lacrimation 
increased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ocular 
icterus 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Vision 
blurred 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Gastrointestin
al disorders 
6 5  
 
 
3 2  
 
 
1
2 
2 4  
 
1
4 
1 1  
 
6  
 
 
 
9 3  
 
 
1
4 
4 1  
 
6 1  
 
 
Abdominal 
discomfort 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Abdominal 
distension 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Abdominal 
hernia 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abdominal 
pain 
 
 
 
 
 
 
 
 
 
 
3 
 
 
 
 
2 
 
 
 
 
1  
 
 
 
2 1  
 
 
2 
2  
 
 
1  
 
 
 
Abdominal 
pain upper 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ascites 
 
1  
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Constipation 
2 2  
 
 
 
 
 
 
 
1 
1  
 
 
2 
 
 
 
 
 
 
 
 
 
2  
 
 
 
3 
1  
 
 
1  
 
 
 
Diarrhoea 
1  
 
 
 
 
 
 
 
 
2 
 
 
 
 
1 
 
 
 
 
2  
 
 
 
 
1  
 
 
1 
 
1  
 
1  
 
 
 
Dry mouth 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dyspepsia 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
Epigastric 
discomfort 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
97 
 
Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
Faeces 
discoloured 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Flatulence 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
 
Gastrointesti
nal 
haemorrhage 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Gingival 
bleeding 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Haemorrhoid
al 
haemorrhage 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Impaired 
gastric 
emptying 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nausea 
 
1  
 
 
1 1  
 
 
2 
 
1  
 
4 
1  
 
 
 
 
 
 
 
2  
 
 
 
3 
 
 
 
 
1 1  
 
 
Oral pain 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stomatitis 
1  
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vomiting 
 
1  
 
 
2 1  
 
 
 
 
2  
 
1 
 
 
 
 
1  
 
 
 
1  
 
 
 
1 
 
 
 
 
2  
 
 
 
General 
disorders and 
administration 
site conditions 
5 5 1  
 
 
2 1  
 
1
0 
3  
 
 
4 
 
 
 
 
9 4 1  
 
5  
1 
 
 
1
1 
2  
 
 
4 1  
 
 
Asthenia 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Chest 
discomfort 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest pain 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Chills 
1  
 
 
 
 
 
 
 
 
1 
 
 
 
 
1 
 
 
 
 
2 1  
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
 
Disease 
progression 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fatigue 
1 2  
 
 
 
1  
 
 
2 
2  
 
 
1 
 
 
 
 
1 2 1  
 
3  
 
 
 
3 
 
 
 
 
1 1  
 
 


MVTH 1 
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98 
 
Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
Hernia pain 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hyperhidrosi
s 
1  
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inflammation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Localised 
oedema 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Malaise 
 
1  
 
 
 
1  
 
 
2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mucosal 
inflammation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Oedema 
peripheral 
1  
1  
 
 
 
 
 
 
1 
 
 
 
 
1 
 
 
 
 
3 1  
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Pain 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
1 
 
 
 
1  
 
 
 
 
 
 
 
Pyrexia 
 
1  
 
 
 
 
 
 
 
2 
1  
 
 
 
 
 
 
 
2  
 
 
 
 
 
 
 
 
2 
1  
 
 
2  
 
 
 
Hepatobiliary 
disorders 
1  
1  
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Hyperbilirubi
naemia 
 
 
1  
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Jaundice 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Immune 
system 
disorders 
 
1 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Infusion 
related 
reaction 
 
1 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Infections and 
infestations 
 
1  
 
 
1  
1  
 
1 
1  
 
 
2 
 
 
 
 
 
 
1  
 
2 2  
 
 
 
2  
 
 
 
 
 
 
 
Candida 
infection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Clostridium 
difficile colitis 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
99 
 
Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
Folliculitis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
Lung 
infection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
Nail infection 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pneumonia 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rhinitis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Sinusitis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Upper 
respiratory 
tract infection 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urinary tract 
infection 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Injury, 
poisoning and 
procedural 
complications 
1  
 
 
 
2  
 
 
 
2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fall 
1  
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Incision 
site 
inflammation 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Wound 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Wound 
complication 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigations 
5  
4  
 
 
 
1  
 
6 
1 4  
 
1 
2 8 1  
1 3 4  
 
5 5 1
0 
1  
1
3 
8 6  
 
5 5 5 1  
Activated 
partial 
thromboplast
in 
time 
prolonged 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
100 
 
Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
Alanine 
aminotransfe
rase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 1  
 
 
 
 
 
 
Alanine 
aminotransfe
rase increased 
1  
 
 
 
 
 
1  
 
 
1  
 
 
 
 
2  
 
 
 
1  
 
 
 
2 
1  
2 
1 2  
 
 
1 2  
 
Aspartate 
aminotransfe
rase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2  
 
 
 
 
 
 
 
Aspartate 
aminotransfe
rase increased 
1  
 
 
 
 
 
 
 
 
1 
 
1  
 
 
 
1  
 
 
 
2  
 
1  
3 
 
 
4 
 
 
 
 
 
2 1  
 
Blood 
alkaline 
phosphatase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Blood 
alkaline 
phosphatase 
increased 
2  
 
 
 
 
 
 
 
 
3 
 
2  
 
 
 
1  
 
 
1 1  
 
2  
2 
 
 
 
1  
 
 
 
1  
 
 
Blood 
bilirubin 
increased 
 
 
2  
 
 
 
 
 
 
1 
 
 
 
 
 
1 3  
 
 
1  
 
 
1 2 1 
 
 
3 
 
 
 
 
1  
2  
 
Blood 
cholesterol 
increased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Blood 
creatinine 
increased 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood 
fibrinogen 
decreased 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
101 
 
Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
Blood lactate 
dehydrogenas
e increased 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood 
phosphorus 
decreased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
International 
normalised 
ratio 
increased 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Lipase 
increased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
1 
 
 
 
1  
 
 
 
 
 
 
 
Lymphocyte 
count 
decreased 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
1  
 
 
 
 
 
 
 
 
1 
 
 
 
 
1  
 
 
 
 
 
 
Neutrophil 
count 
decreased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
1 1  
 
 
 
 
1  
Platelet count 
decreased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
2 
1  
 
 
1  
 
 
 
Weight 
decreased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
1  
 
 
 
 
 
 
 
 
1 
 
 
 
 
1  
 
 
 
White 
blood 
cell 
count 
decreased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
1  
 
1  
 
 
 
Metabolism 
and nutrition 
disorders 
1  
2  
 
 
1 1  
 
9 
 
5  
 
1 
1 1  
 
3  
 
 
 
4 2  
 
 
8 
3 3  
 
2 2 1  
 
Decreased 
appetite 
 
 
 
 
 
 
1  
 
 
1 
 
 
 
 
1 
 
 
 
 
1  
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
102 
 
Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
Dehydration 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hyperglycae
mia 
1  
 
 
 
 
 
 
 
 
 
 
3  
 
 
1 1  
 
 
 
 
 
 
 
1  
 
 
1 
2 2  
 
 
2  
 
 
Hyperkalaem
ia 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Hypermagnes
aemia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Hypertriglyce
ridaemia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Hypoalbumin
aemia 
 
 
1  
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
1  
 
 
1 
 
 
 
 
 
 
 
 
 
Hypocalcaem
ia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
1 
 
 
 
 
 
 
 
 
 
Hypoglycaem
ia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
Hypokalaemi
a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
1 
1  
 
 
1  
1  
 
Hypomagnes
aemia 
 
 
 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
1 
 
 
 
 
 
 
 
 
 
Hyponatraem
ia 
 
 
1  
 
 
 
 
 
 
1 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Hypophospha
taemia 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Iron 
deficiency 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vitamin B12 
deficiency 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vitamin 
D 
deficiency 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
103 
 
Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
Musculoskelet
al 
and 
connective 
tissue 
disorders 
1  
3  
 
2  
 
 
 
2 
 
 
 
 
3 
 
 
 
 
6 2  
 
 
3  
 
 
 
2 
2  
 
 
 
 
 
 
 
Arthralgia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
2  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Back pain 
 
 
1  
 
1  
 
 
 
 
 
 
 
 
1 
 
 
 
 
3  
 
 
 
1  
 
 
 
1 
 
 
 
 
 
 
 
 
 
Muscle injury 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
Muscle 
spasms 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
Muscular 
weakness 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Musculoskele
tal discomfort 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Musculoskele
tal pain 
1  
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myalgia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Neck pain 
 
 
 
 
 
1  
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pain 
in 
extremity 
 
 
1  
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neoplasms 
benign, 
malignant and 
unspecified 
(incl cysts and 
polyps) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Malignant 
neoplasm 
progression 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
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Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
Nervous 
system 
disorders 
1 1  
 
 
2 1  
 
 
 
 
 
 
 
1 
 
 
 
 
2  
 
 
 
 
 
 
 
 
7 
1 2  
 
2  
 
 
 
Balance 
disorder 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confusional 
state 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dizziness 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
Encephalopat
hy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Neuropathy 
peripheral 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 
 
1  
 
1  
 
 
 
Paraesthesia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Peripheral 
sensory 
neuropathy 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
1  
 
 
 
 
 
 
Somnolence 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Syncope 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Psychiatric 
disorders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
1 1  
 
 
1  
 
 
 
2 
 
 
 
 
2  
 
 
 
Depression 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Disorientatio
n 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Insomnia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
2 
 
 
 
 
1  
 
 
 
Renal 
and 
urinary 
disorders 
1  
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
1  
 
 
 
2 1  
 
 
 
 
 
 
 
 
 
 
 
 
Chromaturia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2  
 
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
105 
 
Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
Chronic 
kidney 
disease 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pollakiuria 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Proteinuria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Respiratory, 
thoracic 
and 
mediastinal 
disorders 
2  
 
 
 
5  
 
 
 
5 
 
 
 
 
1 
 
 
 
 
4 2  
 
 
4 2  
 
 
5 
 
3  
 
2  
 
 
 
Cough 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
1 1  
 
 
2 
 
1  
 
1  
 
 
 
Dyspnoea 
1  
 
 
 
1  
 
 
 
1 
 
 
 
 
 
 
 
 
 
2  
 
 
 
1  
 
 
 
 
 
 
 
 
1  
 
 
 
Dyspnoea 
exertional 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Epistaxis 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
 
Hiccups 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nasal 
congestion 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Paranasal 
sinus 
discomfort 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pleural 
effusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Pneumonia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
Pneumonitis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
Productive 
cough 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulmonary 
congestion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulmonary 
embolism 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
106 
 
Adverse events reported by MabVax Therapeutics for their Phase I clinical trial MV-0715-CP-001.01, ClinicalTrials.gov Identifier: NCT02672917 are 
summarized below in Tables 1 to 5 Table 1 All AEs (related and unrelated); highest grade per subject reported by System Organ Class, Preferred 
Term, CTCAE Grade (as 15-December-2017) 
 
Cohort 
A1: 
1mg/kg 
Q2wk 
(n=6) 
Cohort 
A2: 
3mg/kg 
Q2wk 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2 mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 
2 3 4 5 1 
2 3 4 5 1 2 3 4 5 1 2 3 
4 5 1 
2 3 4 5 1 2 3 4 5 
Rhinorrhoea 
 
 
 
 
 
1  
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Skin 
and 
subcutaneous 
tissue 
disorders 
1  
 
 
 
 
 
 
 
 
2 
 
 
 
 
2 
1  
 
 
1  
 
 
 
3  
 
 
 
5 
2  
 
 
4  
 
 
 
Alopecia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 
2  
 
 
1  
 
 
 
Contusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hyperhidrosi
s 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Night sweats 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Pruritus 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
1  
 
 
 
Pruritus 
generalised 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rash 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
2  
 
 
 
Rash maculo-
papular 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
2  
 
 
 
1 
 
 
 
 
 
 
 
 
 
Urticaria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical 
and 
medical 
procedures 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Wound 
drainage 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vascular 
disorders 
 
1 1  
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
3  
 
 
 
1 1 
 
 
3 
1 1  
 
 
1  
 
 
Deep 
vein 
thrombosis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
1  
 
 
 
1  
 
 
 
 
 
 
 
Flushing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
1  
 
 
Hypertension 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
1 
 
 
 
 
 
1  
 
 
 
 
1 
 
 
1 
 
 
 
 
 
 
 
 
 
Hypotension 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
1 
 
1  
 
 
 
 
 
 
*Unaudited data as of 15-Dec-2017 


MVTH 1 
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107 
 
 
 
 
MVT-5873-Related AEs; highest grade per subject reported by System Organ Class, Preferred Term, CTCAE grade (as of 15-December-2017) 
 
Cohort 
A1:  
1mg/kg 
Q2wks 
(n=6) 
Cohort 
A2:  
3 
mg/kg 
Q2wks 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg 
wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 
System Organ 
Class 
   Preferred 
Term 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood 
and 
lymphatic 
system 
disorders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2  
 
 
 
 
1  
 
 
 
 
 
 
 
Anaemia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2  
 
 
 
 
1  
 
 
 
 
 
 
 
Cardiac 
disorders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Sinus 
tachycardia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Tachycardia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eye disorders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Ocular icterus 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Gastrointestin
al disorders 
3 1  
 
 
 
 
 
 
 
3  
 
 
 
5  
 
 
 
 
 
 
 
 
4  
 
 
 
3 1  
 
 
2 1  
 
 
Abdominal 
pain 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Abdominal 
pain upper 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Constipation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
Diarrhoea 
1  
 
 
 
 
 
 
 
 
1  
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
Faeces 
discoloured 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Nausea 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
3  
 
 
 
 
 
 
 
 
1  
 
 
 
1  
 
 
 
1 1  
 
 
Oral pain 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Stomatitis 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
108 
 
MVT-5873-Related AEs; highest grade per subject reported by System Organ Class, Preferred Term, CTCAE grade (as of 15-December-2017) 
 
Cohort 
A1:  
1mg/kg 
Q2wks 
(n=6) 
Cohort 
A2:  
3 
mg/kg 
Q2wks 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg 
wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 
Vomiting 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
1  
 
 
 
1  
 
 
 
1  
 
 
 
General 
disorders and 
administratio
n 
site 
conditions 
1 3  
 
 
 
 
 
 
 
3 3  
 
 
1  
 
 
 
3 2  
 
 
 
 
 
 
 
2 1  
 
 
2  
 
 
 
Chest pain 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chills 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
1  
 
 
 
2 1  
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
Fatigue 
 
2  
 
 
 
 
 
 
 
1 2  
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Malaise 
 
1  
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pyrexia 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
1 1  
 
 
1  
 
 
 
Hepatobiliary 
disorders 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hyperbilirubi
naemia 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immune 
system 
disorders 
 
1 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Infusion 
related 
reaction 
 
1 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Infections and 
infestations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Candida 
infection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigations 
3  
1  
 
 
 
1  
 
1 1 2  
 
 
 
8 1  
 
3 3  
 
4 3 9 1  
7 4 2  
 
3 5 4  
 
Alanine 
aminotransfer
ase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 1  
 
 
 
 
 
 
Alanine 
aminotransfer
ase increased 
 
 
 
 
 
 
 
1  
 
 
1  
 
 
 
 
2  
 
 
 
1  
 
 
 
2 1  
2 2 1  
 
 
1 2  
 


MVTH 1 
Version 1.0: 25-July 2018 
 
109 
 
MVT-5873-Related AEs; highest grade per subject reported by System Organ Class, Preferred Term, CTCAE grade (as of 15-December-2017) 
 
Cohort 
A1:  
1mg/kg 
Q2wks 
(n=6) 
Cohort 
A2:  
3 
mg/kg 
Q2wks 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg 
wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 
Aspartate 
aminotransfer
ase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
Aspartate 
aminotransfer
ase increased 
1  
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
1  
 
 
 
2  
 
1  
3  
 
3  
 
 
 
 
2 1  
 
Blood alkaline 
phosphatase 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Blood alkaline 
phosphatase 
increased 
1  
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
1  
 
 
1  
 
 
2  
2  
 
 
 
 
 
 
 
1  
 
 
Blood 
bilirubin 
increased 
1  
1  
 
 
 
 
 
 
1  
 
 
 
 
 
3  
 
 
1  
 
 
1 2 1  
 
1  
 
 
 
1  
1  
 
Blood 
phosphorus 
decreased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
International 
normalised 
ratio increased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Lipase 
increased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lymphocyte 
count 
decreased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
Platelet count 
decreased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
White 
blood 
cell 
count 
decreased 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Musculoskelet
al 
and 
connective 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
1  
 
 
 
2  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
110 
 
MVT-5873-Related AEs; highest grade per subject reported by System Organ Class, Preferred Term, CTCAE grade (as of 15-December-2017) 
 
Cohort 
A1:  
1mg/kg 
Q2wks 
(n=6) 
Cohort 
A2:  
3 
mg/kg 
Q2wks 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg 
wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 
tissue 
disorders 
Arthralgia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Back pain 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neck pain 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psychiatric 
disorders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Depression 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Renal 
and 
urinary 
disorders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 1  
 
 
 
 
 
 
 
 
 
 
 
 
Chromaturia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2  
 
 
 
 
 
 
 
 
 
 
 
 
 
Proteinuria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
Respiratory, 
thoracic 
and 
mediastinal 
disorders 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
2  
 
1  
 
 
 
Cough 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
1  
 
 
 
Dyspnoea 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pneumonitis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
Skin 
and 
subcutaneous 
tissue 
disorders 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
2  
 
 
 
3  
 
 
 
Alopecia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
Rash 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
2  
 
 
 
Rash maculo-
papular 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
Urticaria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vascular 
disorders 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
Flushing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
111 
 
MVT-5873-Related AEs; highest grade per subject reported by System Organ Class, Preferred Term, CTCAE grade (as of 15-December-2017) 
 
Cohort 
A1:  
1mg/kg 
Q2wks 
(n=6) 
Cohort 
A2:  
3 
mg/kg 
Q2wks 
(n=3) 
Cohort 
A4: 
1mg/kg wkly 
(n=6) 
Cohort 
A5: 
2mg/kg wkly 
(n=6) 
Cohort 
A6: 
3mg/kg wkly 
(n=6) 
Cohort 
A7: 
2.5mg/kg 
wkly 
(n=5) 
Cohort 
B0: 
0.125mg/kg 
wkly 
(n=6) 
Cohort 
B3: 
1mg/kg wkly 
(n=3) 
Grade 
1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 
Hypertension 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
1  
 
 
 
 
1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Unaudited data as of 15-Dec 2017 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
112 
 
Table 5 
Serious Adverse Events Reported as of 15 December 2017 
Manufacturing  
Ctrl No. 
Subject 
ID 
Drug 
Dose 
and 
Frequency 
Cycl
e 
Adverse 
Event 
(Verbatim Term) 
CTCAE Grade 
Relationship 
MVT5873-2016-
001 
02-004 
MVT-5873 
1mg/kg Q2W 
1 
Hypotension 
3 (severe) 
Unrelated 
MVT5873-2016-
002 
02-004 
MVT-5873 
1mg/kg Q2W 
1 
Hyperbilirubinemia 
3 (severe) 
Unrelated 
MVT5873-2016-
003 
01-012 
MVT-5873 
1mg/kg Q2W 
1 
Fever 
2 (moderate) 
Unrelated 
MVT5873-2016-
005 
01-012 
MVT-5873 
1mg/kg Q2W 
2 
Encephalopathy 
5 (death) 
Unrelated 
MVT5873-2016-
006 
02-007 
MVT-5873 
1mg/kg Q2W 
4 
Lung Infection* 
3 (severe) 
Unrelated 
MVT5873-2016-
007 
02-002 
MVT-5873 
1mg/kg Q2W 
1 
Clinical Progression 
of Pancreatic Cancer 
5 (death) 
Unrelated 
MVT5873-2016-
010 
02-028 
MVT-5873 
3mg/kg QW 
1 
Clinical Progression 
of 
Pancreatic 
Carcinoma 
5 (death) 
Unrelated 
MVT5873-2016-
011 
01-025 
MVT-5873 
3mg/kg QW 
2 
Progression 
of 
Disease 
5 (death) 
Unrelated 
MVT5873-2017-
001 
02-034 
MVT-5873 
3mg/kg QW 
1 
Lung Infection 
3 (severe) 
Unrelated 
MVT5873-2017-
002 
02-034 
MVT-5873 
3mg/kg QW 
1 
Lung Infection 
3 (severe) 
Unrelated 
MVT5873-2017-
003 
02-006 
MVT-5873 
3mg/kg Q2W 
10 
Weakness 
3 (severe) 
Unrelated 


MVTH 1 
Version 1.0: 25-July 2018 
 
113 
 
Manufacturing  
Ctrl No. 
Subject 
ID 
Drug 
Dose 
and 
Frequency 
Cycl
e 
Adverse 
Event 
(Verbatim Term) 
CTCAE Grade 
Relationship 
MVT5873-2017-
005 
02-006 
MVT-5873 
3mg/kg Q2W 
10 
Headache 
2 (moderate) 
Unrelated 
MVT5873-2017-
006 
02-006 
MVT-5873 
3mg/kg Q2W 
10 
Clinical 
Disease 
Progression 
5 (death) 
Unrelated 
MVT5873-2017-
009 
01-024 
MVT-5873 
2mg/kg QW 
2 
Malignant neoplasm 
progression 
5 (death) 
Unrelated 
MVT5873-2017-
010 
03-014 
MVT-5873 
1mg/kg QW 
2 
Disease Progression 
5 (death) 
Unrelated 
MVT5873-2017-
012 
01-047 
MVT-5873 
1mg/kg QW 
3 
Fever 
1 (mild) 
Unrelated 
MVT5873-2017-
013 
03-046 
MVT-5873 
1mg/kg Q2W 
5 
Upper 
Gastrointestinal 
Hemorrhage** 
3 (severe) 
Unrelated 
MVT5873-2017-
014 
02-016 
MVT-5873 
1mg/kg QW 
13 
Gastrointestinal 
Bleeding*** 
3 (severe) 
Unrelated 
MVT5873-2017-
015 
02-016 
MVT-5873 
1mg/kg QW 
13 
Vomiting*** 
3 (severe) 
Unrelated 
*Subject 02-007 received a starting dose at 3 mg/kg and then received 6 doses at 1 mg/kg Q2W prior to SAE start date. 
**Subject 03-046 received a starting dose at 2mg/kg QW and then received 1mg/kg Q2W beginning on C1D15 
***Subject 02-016 dose escalated to 2mg/kg QW starting C6D15 through C7D15 and then dose reduced back to original dose of 1mg/kg 
QW 
 
 


MVTH 1 
Version 1.0: 25-July 2018 
 
114 
 
 APPENDIX C: INVESTIGATOR AGREEMENT 
This form can be used to send to Participating site PIs if the CCR is the coordinating center for 
the protocol. 
I have received and reviewed the Investigator Brochure for (insert Study Agent) 
 
I have read this protocol and agree that the study is ethical. 
 
I agree to conduct the study as outlined and in accordance with all applicable regulations and 
guidelines.  
 
I agree to maintain the confidentiality of all information received or developed in connection with 
this protocol.   
 
Protocol Title: 
 
 
Protocol Version Date: 
 
 
_______________________________________            
 
___________________      
Signature of Principal Investigator 
 
 
 
 
 
Date 
 
 
_________________________________________ 
Name of Principal Investigator (printed or typed) 
 

ICF_001.pdf: 
PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 08/10/2020
Page 1 of 19
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
PRINCIPAL INVESTIGATOR:    Jonathan M. Hernandez, MD 
STUDY TITLE:                                Perioperative MVT-5873, a Fully Human Monoclonal   
                                                            Antibody Against a CA 19-9 Epitope, for Operable CA 
                                                            19-9 Producing Pancreatic Cancers, 
                                                            Cholangiocarcinomas, and Metastatic Colorectal Cancers
STUDY SITE:                                   NIH Clinical Center
Cohort:                                                Affected Patients
Consent Version:                                08/10/2020
WHO DO YOU CONTACT ABOUT THIS STUDY? 
Jonathan M. Hernandez, MD, by phone at 240-760-6072 or email at jonathan.hernandez@nih.gov
This consent form describes a research study and is designed to help you decide if you would like 
to be a part of the research study.  
You are being asked to take part in a research study at the National Institutes of Health (NIH). 
Members of the study team will talk with you about the information described in this document. 
Some people have personal, religious, or ethical beliefs that may limit the kinds of medical or 
research treatments they would want to receive (such as blood transfusions). Take the time needed 
to ask any questions and discuss this study with NIH staff, and with your family, friends, and 
personal health care providers. Taking part in research at the NIH is your choice.
If the individual being asked to participate in this research study is not able to give consent to be 
in this study, you are being asked to give permission for this person as their decision-maker. The 
term “you” refers to you as the decision-maker and/or the individual being asked to participate in 
this research, throughout the remainder of this document. 
IT IS YOUR CHOICE TO TAKE PART IN THE STUDY
You may choose not to take part in this study for any reason. If you join this study, you may change 
your mind and stop participating in the study at any time and for any reason. In either case, you 
will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you 
must be taking part in a study or are being considered for a study. If you do choose to leave the 
study, please inform your study team to ensure a safe withdrawal from the research.  
WHY IS THIS STUDY BEING DONE?
In this study we will investigate safety of using MVT-5873 given at the time of surgery to remove 
your cancer and whether MVT-5873 can increase the time it takes for your disease to get worse. 
MVT-5873 is an investigational (has not been approved by the FDA) agent. This is the first study 
in which the MVT-5873 is being given to humans prior to and after surgery.
IRB NUMBER: 19C0039
IRB APPROVAL DATE: 09/15/2020


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 08/10/2020
Page 2 of 19
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
One of the features of tumors of the gastrointestinal tract is the presence of a molecule called CA 
19-9 in the tumors and in the blood. MVT-5873 was designed to target and block CA 19-9. We 
believe that MVT-5873 can be more effective in patients with CA 19-9 positive tumors, but we do 
not know for sure. Considering this, we will enroll people with specific level of CA 19-9 in 
patients’ blood. 
This study has two parts: safety and efficacy.
First, we are going to evaluate the safety of using MVT-5873 prior to and after surgery to remove 
your tumor. Increasing doses of MVT-5873 will be given to participants in the study to find the 
highest dose of MVT-5873 that people can tolerate when given at the time of surgery. 
Secondly, we will study if the recommended dose of MVT-5873 at the time of surgery can increase 
the time it takes for your disease to get worse.
WHY ARE YOU BEING ASKED TO TAKE PART IN THIS STUDY?
You are being asked to take part in this study because you have been diagnosed with pancreatic 
cancer, bile duct cancer or colorectal cancer with metastases to the liver, and you have a certain 
level of CA 19-9 in your blood.
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? 
Up to 105 people will be enrolled on the study, but because not everyone will be eligible, it is 
expected that about 83 will be treated.
DESCRIPTION OF RESEARCH STUDY
Before you begin the study
Before you begin this study, you will need to have the following exams and tests to make sure you 
are eligible for this study. These exams and tests are part of regular cancer care. If you recently 
had some of the tests, they may not need to be repeated. You will be removed from the study if 
you are not eligible:

A review of any past or current medical conditions, demographic data (your sex, age, 
race/ethnicity), medicines you have been taking, cancer and its treatment history.

Physical examination, including height, weight and vital signs.

Electrocardiogram (EKG – a record of your heartbeat) to evaluate your heart.

Review of your symptoms and your ability to perform your normal activities.

Imaging Assessments – a computed tomographic scan (CT) that produces a picture of your 
body using a small amount of radiation or magnetic resonance imaging (MRI) that uses a 
magnetic field to produce an image of your body. These will be used to examine your chest, 
abdomen, and pelvis.

Routine blood tests:
o
Tests to find out if you are anemic, have low blood counts, your blood is clotting 
normally and if your liver, kidneys, and other organs are working well.
IRB NUMBER: 19C0039
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o
To look at the CA 19-9 level in your blood.
o
Tests for Hepatitis B and C. If you are infected with Hepatitis B or C you will not 
be able to participate in this study as it will pose additional risk to you.  We will tell 
you what the results mean, how to find care, how to avoid infecting others, and the 
importance of informing your partners at possible risk because of your infection.

Serum or urine pregnancy test if you are a woman who can have children.

You will be asked to provide confirmation of your diagnosis. If tumor sample from a 
previous surgery/biopsy is not available, we will perform a biopsy (collect a sample of your 
tumor) to confirm your diagnosis.
You will also be asked to co-enroll on the Surgical Oncology Program’s tissue collection protocol 
13C0176 (“Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or 
Surgical Resection of Solid Tumors”) so that any remaining tumor or blood samples that were 
collected as a part of this study can be used for future research when this study ends. 
During the Study 
During the study MVT-5873 treatment MVT-5873 will be administered to you through an IV 
(intravenous catheter, a small plastic tube that is put into a vein, usually in your arm) before and 
after surgery.
The first infusion will be done 3 to 7 days before surgery (Day -3). This infusion will last 
approximately 2 hours. If tolerated, the infusion time for subsequent infusions may be shortened.
After your recover from surgery (approximately 1 to 2 weeks after the operation) we will continue 
administration of MVT-5873 on a 3-week (21 day) cycle basis. During the first 21-day cycle, two 
infusions will be given a week apart on Day 1 and Day 8, and then every 2 weeks during Cycle 2.
Surgery
In this study you will be admitted to the hospital for surgery. Most patients are admitted the evening 
before their operation. Your physician will explain the surgical procedure and will answer any 
questions you may have. You will be asked to sign a separate consent for the operation. 
You will undergo a major surgical operation to remove as many of your visible cancer tumors as 
possible.  
Recovery 
After the operation, you will be admitted to the Intensive Care Unit (ICU) where you will be 
monitored closely for 1-4 days.  As with any major operation, you may have a breathing tube and 
be connected to a breathing machine for 1-2 days following the operation.  You will have a tube 
in your stomach, a catheter (tube) in your bladder and several IVs during this period. As soon as 
you are able, you will be helped to get out of bed, to cough and take deep breaths and to walk.  
Once your bowel function has returned to normal, you will be allowed to eat – this usually takes 
5-7 days.  
When your condition is stable, you will be transferred to the regular patient care unit until you are 
ready to be discharged to home, usually 7-14 days following the operation.  Throughout your 
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hospitalization, you will receive pain medications, IV fluids, antibiotics, and blood transfusions as 
necessary.   
Ongoing Procedures 
While you are on the treatment, every time you visit the Clinical Center for MVT-5873 infusion 
and surgery, you will have:

Review of current medical conditions and medicines you are taking. 

Physical examination, including weight and vital signs.

Review of your symptoms and your ability to perform your normal activities.

Routine blood tests to find out if you are anemic, have low blood counts, your blood is 
clotting normally and if your liver, kidneys, and other organs are working well.
During these visits you will also have the following done for research purposes and to check if the 
treatment is working:

Research blood tests to look at the CA 19-9 level in your blood. (You will have your CA 
19-9 level collected before the study drug infusion and 2 hours after the study drug 
infusion.)

Imaging Assessments – a computed tomographic scan (CT) that produces a picture of your 
body using a small amount of radiation or magnetic resonance imaging (MRI) that uses a 
magnetic field to produce an image of your body. These will be used to examine your chest, 
abdomen, pelvis.
Research Tests
In addition to the tests that we will conduct to determine whether you are having side effects or if 
you are responding to the study therapy, we will also collect samples from you for purposes of 
research only. Some of the analyses will be done outside of the NIH, but your samples will not 
contain any information that can identify you. 
These studies include:

Collection of blood before treatment, on day of surgery, on Day 1 of Cycle 1, and at the 
end of treatment visit to: 
o
Measure the amount of tumor cells in your blood, and study how these tumor cells 
respond to the study therapy.

During surgery, we will collect tissue samples of your tumor and normal liver to study: 
o
How efficiently your genes are working, the difference in proteins, metabolism and 
microenvironment in your tumor compare to normal tissue. 
o
The long-term effect of treatment on proteins, metabolism and microenvironment in 
your tumor and normal liver tissue. Your liver tissue will be used in the development 
of a “liver model” – and your samples will be kept “live” in a special device.   
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o
The molecular mechanisms of tumor development, growth, and response to treatment. 
We will keep your samples “live” for a short period of time (up to 4 days) and use 
these samples in the development “SMART System models” - which can test multiple 
treatments and allow us to study the effect of each treatment and how the treatments 
compare to each other. 
Genetic testing and return of results
Your tissue samples contain genes, which are made up of DNA (deoxyribonucleic acid) and 
transcript of these genes made of RNA (ribonucleic acid) which serves as the "instruction book" 
for the cells that make up our bodies. We will use the tissue samples you provided to learn about 
how the genes in your tumor compare to genes in normal tissue. Your tissue will help us study 
how genes might play a role in colon cancer and other diseases. We will not share the results of 
these research tests with you.
When we are conducting the above genetic tests, it is possible that we could identify changes in 
other parts of your RNA that are not related to this research. These are known as “incidental 
medical findings”:

Changes in genes that are related to diseases other than cancer. 

Changes in genes that are not known to cause any disease. These are known as normal 
variations. 

Changes in genes that are new and of uncertain clinical importance. This means that we do 
not know if they could cause or contribute to a disease or if they are normal variations.
However, the analyses that we perform in our laboratory are for research purposes only; they are 
not nearly as sensitive as the tests that are performed in a laboratory that is certified to perform 
genetic testing. Changes that we observe unrelated to our research may or may not be valid. 
Therefore, we do not plan to inform you of the results of testing on your tissue and blood that is 
performed in our research lab. However, in the unlikely event that we discover a finding that is 
believed to be clinically important based on medical standards at the time that we first analyze 
your results, we will contact you. This could be many years in the future. We will ask you to have 
an additional tube of blood drawn to verify the findings we have seen in our lab. If the results are 
verified, you will be re-contacted and offered a genetic counseling here at Clinical Center (no 
charge) or referral to an outside genetic healthcare provider (at your expense) to discuss the results.
When you are finished taking the drug (treatment)
After completion of the therapy, you will be invited for follow up visits approximately 1 week 
(end of treatment) and 1 month after the last day you take the study drug. At these visits, you will 
have the following tests: 

Review of current medical conditions and medicines you are taking. 

Physical examination, including weight and vital signs.

Review of your symptoms and your ability to perform your normal activities.

Routine blood tests:
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o
Tests to find out if you are anemic, have low blood counts, your blood is clotting 
normally and if your liver, kidneys, and other organs are working well.

Imaging Assessments – a computed tomographic scan (CT) that produces a picture of your 
body using a small amount of radiation or magnetic resonance imaging (MRI) that uses a 
magnetic field to produce an image of your body. These will be used to examine your chest, 
abdomen, pelvis (only at 1-week visit).
During these visits you will also have the following tests for research purposes:

Research blood tests to look at the CA 19-9 level in your blood. (This will also be done 
during your long term follow up.)
If you are not able to come to these visits, we may be able to call/videocall you and arrange for 
you to have a visit with a home physician, with certain tests done at outside labs nearer to your 
home and the results sent to us instead. Your healthcare team will let you know more if this is the 
case. We will contact you by telephone/videocall or email to ask if you have side effects.  
After that, we will contact you by telephone/videocall or email every four months to determine 
your health status and to find out about any new cancer treatments that you have begun.  This will 
continue for the rest of your life or until the study is stopped.  
BIRTH CONTROL, RISKS OF PREGNANCY AND BREASTFEEDING
There may be a high risk that the study treatment may damage an unborn child (embryo or fetus); 
therefore, if you are a female, you must not get pregnant while in this study. This is why the study 
doctor will ask if you are using an acceptable method of birth control (contraception) and why you 
should inform your doctor if you think you may be pregnant.
The only certain way to not get pregnant is to not have sex. If you are a female and choose to have 
sex, you must use a type of birth control listed below while in this study (and for 3 months after 
your last dose). If you become pregnant during the study, you will be discontinued from the study, 
and your physician will need to follow up with your pregnancy and your child’s health.
Acceptable methods of birth control for this study include:

Norplant

Birth control pills plus another method (i.e. condom)

Birth control patch

IUD (intrauterine device)

Depo-Provera

Sterilization

Abstinence

Condoms with spermicide
If you are a woman of childbearing age, you must use birth control for the entire duration of the 
study treatment and for 3 months afterwards or you cannot be in the study. Hormonal methods 
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(birth control pill, etc.), double-barrier methods (condoms with spermicidal, sponge with 
spermicidal, or diaphragm with spermicidal), or abstinence may be used. Your doctor will discuss 
these with you. Some methods of birth control will not work when you are taking certain drugs. 
Be aware that you can still become pregnant even if you use an acceptable birth control method.
The study doctor will require some women who join the study to have pregnancy tests before the 
study. A pregnancy test does not keep you from becoming pregnant.
If you are a man, there may be risks to an unborn baby you father during or after the study; 
therefore, you must use birth control if you choose to have sex with women during the study 
treatment (and for 3 months after your last dose). You must also not donate sperm during the study 
treatment and for at least 3 months after completion of the study. If you are a male with a partner 
who could become pregnant, you must use condoms and make sure your partner is also using 
effective birth control during the study. If your partner becomes pregnant, you must tell the study 
doctor immediately.
If you think you are or your partner is pregnant during the study, you must tell the study doctor 
immediately. If you become pregnant, you will have to stop the study treatment. The study doctor 
may ask for information about the pregnancy and the birth of the baby. The study doctor may share 
this information with the sponsor and the IRB (organization overseeing the study).
Even if you use birth control during the study, there is a chance you could become pregnant. If you 
are pregnant or become pregnant during the study, the drug or procedure may involve risks to the 
unborn baby, which are currently unforeseeable.
A pregnancy test can be wrong. If you become pregnant during the study, call the study doctor at 
once. You will not receive any further treatments with the study drug.
You cannot be in the study if you are pregnant or breastfeeding. It is not known whether the study 
drug is safe for breast-fed babies. Therefore, if you are breastfeeding a child, then you must stop 
breastfeeding.
RISKS OR DISCOMFORTS OF PARTICIPATION
If you do not understand what any of these side effects mean, please ask the study doctor or study 
staff to explain these terms to you.
Because the study drug is investigational, all of its side effects may not be known. There may be 
rare and unknown side effects, some of which may be irreversible and/or life-threatening. You 
should report all side effects that you experience to the study doctor.
You may have side effects while on the study. Everyone taking part in the study will be watched 
carefully for any side effects. However, doctors do not know all the side effects that may happen. 
Side effects may be mild or very serious. The study doctor may give you medicines to help lessen 
side effects.
You must tell the study doctor or study staff about all side effects that you have. If you are not 
honest about your side effects, it may not be safe for you to stay in the study.
If you choose to take part in this study, there is a risk that:

There may be complications that preclude a surgery with a chance of cure.
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
There may be complications that preclude a treatment with known survival benefit.

Based on the observation of liver toxicity in prior studies:
o
The removal of your tumor may be delayed.
o
The start of chemotherapy after your operation may be delayed.

A delay in the start of standard adjuvant chemotherapy may affect your outcome.

You may lose time at work or home.

You may spend more time in the hospital or doctor’s office than usual.

You may be asked sensitive questions that you normally do not discuss.
The drugs used in this study may affect how different parts of your body work, such as your liver, 
kidneys, heart, and blood. The study doctor will be testing your blood and will let you know if 
changes occur that may affect your health.
Here are important points about side effects:

The study doctors do not know who will or will not have side effects.

Some side effects may go away soon, some may last a long time, or some may never go 
away.

Some side effects may interfere with your ability to have children.

Some side effects may be serious and may even result in death.
Here are important points about how you and the study doctor can make side effects less of a 
problem:

Tell the study doctor if you notice or feel anything different.

The study doctor may be able to treat some side effects.

The study doctor may adjust the study drugs to try to reduce side effects.

There might be other side effects that researchers do not yet know about.  If important new 
side effects are found in other patients participating in this study, the study doctor will 
discuss these with you.
MVT-5873
To date, forty-nine (49) patients have received the study drug MVT-5873. All possible side 
effects of the study drug are not yet known. In this limited number of patients, the study drug 
has been known to cause side effects typically seen with other antibodies. The side effects have 
gone away after the study drug is stopped, but some side effects could be serious and long lasting.

Allergic reactions, consisting of one or more of the following:
o
Fever
o
Chills
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o
Nausea
o
Vomiting
o
Headache
o
Rashes, including hives
o
Dizziness
o
Difficulty breathing
o
Shortness of breath
o
Wheezing
o
Chest tightness
o
Lowered blood pressure

Diarrhea or loose stools

Fatigue

Fever

Increase in blood levels that measure liver function

Pneumonitis (inflammation of the lung wall) was observed in some patients receiving 
MVT-5873 in combination with the gemcitabine plus nab-paclitaxel chemotherapy
Let your study doctor know of any questions you have about possible side effects. You can ask the 
study doctor questions about side effects at any time.
When you take more than one drug at a time, the side effects can be worse or different than if you 
take either drug by itself.
Until you know how the study drug will affect you, you should use caution by avoiding stairs, not 
driving a car or working with machinery.
You may form antibodies to the drug. An antibody is a type of protein that helps protect the body 
against attack by bacteria and viruses. There is also a small chance that if you have these 
antibodies, this drug or similar drugs will not work for you in the future.
Please tell the study doctor or study staff right away if you have any side effects. Please tell them 
if you have any other problems with your health or the way you feel during the study, regardless 
of whether or not you think these problems are related to the investigational drug.
Could I have an allergic reaction?
Sometimes people have allergic reactions to drugs. If you have a very bad allergic reaction, you 
could die. Some things that happen during an allergic reaction are:

A rash

Having a hard time breathing

Wheezing
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
A sudden drop in blood pressure (making you feel dizzy or lightheaded)

Swelling around the mouth, throat or eyes

A fast pulse

Sweating
You should get medical help and contact the study doctor or study staff if you have any of these 
or any other side effects during the study.
Could I have any other problems with my health if I do this research study?
It is possible that receiving this study drug with your regular medications or supplements may 
change how the study drug, your regular medications, or your regular supplements work. It is very 
important that you tell the study doctor about all medications or supplements you are taking during 
the study.
ADDITIONAL RISKS OR DISCOMFORTS
Blood Samples 
There may be side effects of having blood drawn taken by single needle-sticks or by a tube that is 
left in your arm such as:

Fainting

Redness

Pain

Bruising

Bleeding

Infection

Blood clots, which may cause inflammation, swelling and pain 
If you feel faint tell the study staff right away.
Risks of using an Intravenous (IV) Catheter

Infection

Pain

Redness

Bruising

Vein irritation from the fluids or medication being given

Local swelling due to IV fluid accidentally entering the tissue rather than the vein

Blood clots, which may cause inflammation, swelling and pain
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Tissue Collection Risk
We will use some of the tissue we collect from your liver during your standard of care surgery for 
research.  If you do not need to remove a part of your liver as part of your treatment, we will take 
a small sample from your liver for research purposes during the standard of care surgery on your 
pancreas.  There is a slight risk this may cause additional bleeding, infection or damage to your 
liver. 
Risks from Biopsy 
This procedure usually causes only brief discomfort at the site from which the biopsy is taken. 
Rarely, infection or bleeding may occur at the needle site. Tumor biopsy will be done by a 
specialist using the CT scanner or ultrasound to guide the biopsy needle into the tumor to ensure 
accuracy. We will give you more information about the risks of radiation during the CT guided 
biopsies on this study in this consent form below.
Surgery
The risks of undergoing a resection will be specific to your operation. Dr. Hernandez will discuss 
the specific risks in detail during the procedural consent, which will be obtained separately from 
the study consent in accordance with NIH policy.
Urine Collection
There is no physical risk involved with urine collection.
Electrocardiogram (EKG)
This test evaluates your heart rate and rhythm by measuring electrical impulses from the heart 
through electrodes that are placed on the skin.  You must lie down and be still without talking 
during the 5 minutes the EKG is being recorded. This procedure is associated with minimal 
discomfort.
Scans and Contrast
CT and MRI scans are common standard imaging tests used in the diagnosis of cancer. The most 
common discomfort is the length of time a patient must lay still during a scan. Occasionally, a 
patient may become uncomfortable with the closed space of the machines, particularly the MRI. 
If this occurs, your doctor can order a medicine to help you relax during this scan. If a contrast 
agent (the special dye) is given with the scan there is a small risk of having a reaction to the 
contrast. In that small group of patients who have a reaction, the most common symptoms are 
nausea, pain in the vein where the contrast was given, a metallic or bitter taste in the mouth, and a 
warm or flushing feeling that lasts from 1-3 minutes. Rarely do these symptoms require any 
treatment. In very rare cases, people have had severe reactions that affect their breathing and heart 
rhythm. If you have had a reaction in the past, be sure to tell you doctor or nurse about it. 
An IV line may need to be inserted for administration of the contrast agent or anesthetic.  This can 
cause pain at the site where the IV is placed and carries a small risk of bruising or infection.
Mild symptoms from gadolinium infusion occur in fewer than 1% of those who receive it and 
usually go away quickly.  Mild symptoms may include coldness in the arm during the injection, a 
metallic taste, headache, and nausea.  In an extremely small number, fewer than one in 300,000 
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people, more severe symptoms have been reported including shortness of breath, wheezing, hives, 
and lowering of blood pressure. You should not receive gadolinium if you previously had an 
allergic reaction to it.  You will be asked about such allergic reactions before gadolinium is given.   
People with kidney disease are at risk for a serious reaction to gadolinium contrast called 
“nephrogenic systemic fibrosis” which has resulted in a very small number of deaths.  A blood test 
of your kidney function may be done within the month before an MRI scan with gadolinium 
contrast. You will not receive gadolinium for a research MRI scan if your kidney function is not 
normal or if you received gadolinium within the previous month. 
Most of the gadolinium contrast leaves the body in the urine.  However, the FDA recently issued 
a safety alert that indicates small amounts of gadolinium may remain in the body for months to 
years.  The effects of the retained gadolinium are not clear. At this time, retained gadolinium has 
not been linked to health risks in people whose kidneys work well. Some types of gadolinium 
contrast drugs are less likely to remain than others.  In this study, we will use the gadolinium 
contrast drugs that are less likely to remain, whenever possible. We will also give you additional 
information called a “Medication Guide.” Upon request, we will give you individual information 
about retained gadolinium we see on your studies.
Patients with a cardiac pacemaker, neural pacemaker, some types of surgical clips, cochlear 
implants, foreign metal objects, permanent retainers, or any iron-containing material within the 
body should not undergo MRI, because of the effect of the strong magnet on these objects.
What are the risks of radiation from being in the study?
During your participation in this research study, you will be exposed to radiation from CT scans.  
The amount of radiation exposure you will receive from these procedures is equal to approximately 
8.5 rem. A rem is a unit of absorbed radiation. 
Every day, people are exposed to low levels of radiation that come from the sun and the 
environment around them.  The average person in the United States receives a radiation exposure 
of 0.3 rem per year from these sources.  This type of radiation is called “background radiation.”  
This study will expose you to more radiation than you get from everyday background radiation. 
No one knows for sure whether exposure to these low amounts of radiation is harmful to your 
body. 
The CT scans that you get in this study will expose you to the roughly the same amount of radiation 
as 28.3 years’ worth of background radiation. Being exposed to too much radiation can cause 
harmful side effects such as an increase in the risk of cancer.  The risk depends on how much 
radiation you are exposed to. Please be aware that about 40 out of 100 people (40%) will get cancer 
during their lifetime, and 20 out of 100 (20%) will die from cancer. The risk of getting cancer from 
the radiation exposure in this study is 0.9 out of 100 (0.9%) and of getting a fatal cancer is 0.4 out 
of 100 (0.4%).
Psychological or Social Risks Associated with Return of Incidental or Secondary Findings
As part of the research study, it is possible that you could learn that you have genetic risks for 
another disease or disability. This may be upsetting and, depending on what you learn, might create 
a need to make challenging decisions about how to respond. 
IRB NUMBER: 19C0039
IRB APPROVAL DATE: 09/15/2020


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 08/10/2020
Page 13 of 19
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Although your genomic information is unique to you, you share some genomic similarities with 
your children, parents, brothers, sisters, and other blood relatives. Therefore, learning your 
research results could mean something about your family members and might cause you or your 
family distress. Before joining the study, it may be beneficial to talk with your family members 
about whether and how they want you to share your results with them. 
Privacy Risks Associated with Return of Incidental or Secondary Findings
Although your genetic information is unique to you, you do share some genetic information with 
your children, parents, brothers, sisters, and other blood relatives. Consequently, it may be possible 
that genetic information from them could be used to help identify you.  Similarly, it may be 
possible that genetic information from you could be used to help identify them.  Patterns of genetic 
variation also can be used by law enforcement agencies to identify a person or his/her blood 
relatives.  
Protections Against Misuse of Genetic Information 
This study involves genetic testing on samples.  Some genetic information can help predict future 
health problems of you and your family and this information might be of interest to your employers 
or insurers. The Genetic Information Nondiscrimination Act (GINA) is a federal law that prohibits 
plans and health insurers from requesting genetic information or using genetic information. It also 
prohibits employment discrimination based on your health information. However, GINA does not 
address discrimination by companies that sell life insurance, disability insurance, or long-term care 
insurance. GINA also does not protect you against discrimination based on an already-diagnosed 
condition or disease that has a genetic component.
POTENTIAL BENEFITS OF PARTICIPATION
Are there benefits to taking part in this study? 
The aim of this study is to see if this experimental treatment will make persons with your disease 
live longer. 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 treatment’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. 
ALTERNATIVE APPROACHES OR TREATMENTS
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:

Getting treatment or care for your cancer without being in a study.

Taking part in another study.

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.
IRB NUMBER: 19C0039
IRB APPROVAL DATE: 09/15/2020


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 08/10/2020
Page 14 of 19
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Please talk to your doctor about these and other options.
STOPPING THERAPY 
Your doctor may decide to stop your therapy for the following reasons:

if he/she believes that it is in your best interest

if your disease gets worse during treatment 

if you develop unacceptable toxicity to study treatment

if you need chemotherapy

if you become pregnant

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. 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. 
USE OF SPECIMENS AND DATA FOR FUTURE RESEARCH
Your samples will be stored for future use under the seperate specimen collection protocol 
(13C0176) in which you have agreed to be co-enrolled.
To advance science, it is helpful for researchers to share information they get from studying human 
data. 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 data stored in scientific databases to advance science 
and learn about health and disease. 
IRB NUMBER: 19C0039
IRB APPROVAL DATE: 09/15/2020


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 08/10/2020
Page 15 of 19
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
We plan to keep some of your specimens and data that we collect on this study 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 they may be used for future research on any topic and shared broadly 
for research purposes. Your 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 you 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 with 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.
Genomic Data Sharing
As part of this research study, we will put your genomic data in a large database for broad sharing 
with the research community. These databases are commonly called data repositories. The 
information in this database will include but is not limited to genetic information, race and 
ethnicity, and sex.  If your individual data are placed in one of these repositories, they will be 
labeled with a code and not with your name or other information that could be used to easily 
identify you, and only qualified researchers will be able to access them. These researchers must 
receive prior approval from individuals or committees with authority to determine whether these 
researchers can access the data.
Summary information about all of the participants included in this study (including you) is being 
placed in a database and will be available through open access. That means that researchers and 
non-researchers will be able to access summary information about all the participants included in 
the study, or summary information combined from multiple studies, without applying for 
permission. The risk of anyone identifying you with this information is very low.
NIH policies require that genomic data be placed in a repository for sharing. Therefore, we cannot 
offer you a choice of whether your data will be shared.  If you do not wish to have your data placed 
in a repository, you should not enroll in this study.
COMPENSATION, REIMBURSEMENT, AND PAYMENT
Will you receive compensation for participation in the study?
Some NIH Clinical Center studies offer compensation for participation in research. The amount 
of compensation, if any, is guided by NIH policies and guidelines.
You will not receive compensation for participation in this study. 
Will you receive reimbursement or direct payment by NIH as part of your participation?
Some NIH Clinical Center studies offer reimbursement or payment for travel, lodging or meals 
while participating in the research. The amount, if any, is guided by NIH policies and guidelines.
IRB NUMBER: 19C0039
IRB APPROVAL DATE: 09/15/2020


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 08/10/2020
Page 16 of 19
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
The NCI generally does not cover expenses during screening.  If you are scheduled for and begin 
treatment, the NCI will cover the cost for some of your expenses. Some of these costs may be paid 
directly by the NIH and some may be reimbursed after you have paid.  Someone will work with 
you to provide more information.
Will taking part in this research study cost you anything? 
NIH does not bill health insurance companies or participants for any research or related clinical 
care that you receive at the NIH Clinical Center. 

If some tests and procedures are performed outside the NIH Clinical Center, you may have 
to pay for these costs if they are not covered by your insurance company.

Medicines that are not part of the study treatment will not be provided or paid for by the 
NIH Clinical Center.

Once you have completed taking part in the study, medical care will no longer be provided 
by the NIH Clinical Center.
CLINICAL TRIAL REGISTRATION AND RESULTS REPORTING 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time.
CONFIDENTIALITY PROTECTIONS PROVIDED IN THIS STUDY  
Will your medical information be kept private? 
We will do our best to make sure that the personal information in your medical record will be kept 
private.  However, we cannot guarantee total privacy.  Organizations that may look at and/or copy 
your medical records for research, quality assurance, and data analysis include:

The NIH and other government agencies, like the Food and Drug Administration (FDA), 
which are involved in keeping research safe for people.

National Institutes of Health Intramural Institutional Review Board

Qualified representatives from AAIPharma, the pharmaceutical company who produces 
MVT-5873.  
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.
If we share your specimens or data with other researchers, in most circumstances we will remove 
your identifiers before sharing your specimens or data. You should be aware that there is a slight 
possibility that someone could figure out the information is about you. 
Further, the information collected for this study is protected by NIH under a Certificate of 
Confidentiality and the Privacy Act. 
IRB NUMBER: 19C0039
IRB APPROVAL DATE: 09/15/2020


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 08/10/2020
Page 17 of 19
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Certificate of Confidentiality
To help us protect your privacy, the NIH Intramural Program has received a Certificate of 
Confidentiality (Certificate). With this certificate, researchers may not release or use data or 
information about you except in certain circumstances.  
NIH researchers must not share information that may identify you in any federal, state, or local 
civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a 
court.  
The Certificate does not protect your information when it:  
1. is disclosed to people connected with the research, for example, information may be used 
for auditing or program evaluation internally by the NIH; or 
2. is required to be disclosed by Federal, State, or local laws, for example, when information 
must be disclosed to meet the legal requirements of the federal Food and Drug 
Administration (FDA); 
3. is for other research;
4. is disclosed with your consent. 
The Certificate does not prevent you from voluntarily releasing information about yourself or your 
involvement in this research. 
The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or 
others including, for example, child abuse and neglect, and by signing below you consent to those 
disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice 
and Acknowledgement of Information Practices consent.
Privacy Act
The Federal Privacy Act generally protects the confidentiality of your NIH medical records we 
collect under the authority of the Public Health Service Act.  In some cases, the Privacy Act 
protections differ from the Certificate of Confidentiality.  For example, sometimes the Privacy Act 
allows release of information from your medical record without your permission, for example, if 
it is requested by Congress. Information may also be released for certain research purposes with 
due consideration and protection, to those engaged by the agency for research purposes, to certain 
federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect 
reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is 
involved in a lawsuit.  However, NIH will only release information from your medical record if it 
is permitted by both the Certificate of Confidentiality and the Privacy Act.
POLICY REGARDING RESEARCH-RELATED INJURIES  
The NIH Clinical Center will provide short-term medical care for any injury resulting from your 
participation in research here. In general, no long-term medical care or financial compensation for 
research-related injuries will be provided by the NIH, the NIH Clinical Center, or the Federal 
Government. However, you have the right to pursue legal remedy if you believe that your injury 
justifies such action.
IRB NUMBER: 19C0039
IRB APPROVAL DATE: 09/15/2020


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 08/10/2020
Page 18 of 19
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
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, Dr. Jonathan 
Hernandez, MD, jonathan.hernandez@nih.gov, 240-760-6072. You may also call the NIH Clinical 
Center Patient Representative at 301-496-2626, or the NIH Office of IRB Operations at 301-402-
3713, if you have a research-related complaint or concern.
CONSENT DOCUMENT 
Please keep a copy of this document in case you want to read it again.
IRB NUMBER: 19C0039
IRB APPROVAL DATE: 09/15/2020


PATIENT IDENTIFICATION
Consent to Participate in a Clinical Research Study
NIH-2977 (4-17)
File in Section 4: Protocol Consent (2)
Version Date: 08/10/2020
Page 19 of 19
CC ICF template v. 09.27.19
MEDICAL RECORD
CONSENT TO PARTICIPATE IN AN NIH CLINICAL RESEARCH STUDY
Adult Research Participant: I have read the explanation about this study and have been given the opportunity 
to discuss it and to ask questions. I consent to participate in this study.
Signature of Research Participant
Print Name of Research Participant
Date
Legally Authorized Representative (LAR) for an Adult Unable to Consent: I have read the explanation 
about this study and have been given the opportunity to discuss it and to ask questions. I am legally authorized 
to make research decisions on behalf of the adult participant unable to consent and have the authority to provide 
consent to this study. As applicable, the information in the above consent was described to the adult participant 
unable to consent who agrees to participate in the study.
Signature of LAR
Print Name of LAR
Date
Investigator:
Signature of Investigator
Print Name of Investigator
Date
Witness to the oral short-form consent process only: This section is only required if you are doing the oral 
short-consent process and this English consent form has been approved by the IRB for use as the basis of 
translation.
Witness:
Signature of Witness*
Print Name of Witness
Date
*NIH ADMINISTRATIVE SECTION TO BE COMPLETED REGARDING THE USE OF AN 
INTERPRETER:
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent and served as a witness. The investigator obtaining consent may not 
also serve as the witness.
An interpreter, or other individual, who speaks English and the participant’s preferred language facilitated
the administration of informed consent but did not serve as a witness. The name or ID code of the person 
providing interpretive support is:
.
IRB NUMBER: 19C0039
IRB APPROVAL DATE: 09/15/2020