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6 data collection and evaluation

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.  
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**.
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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
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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:
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:
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- during hospitalization for surgical

o ≤ Grade 3 events except **unexpected** events that are possibly or definitely related to the research.
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- post-operative recovery period (following

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.
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data sharing plans 6.2.1 human

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.
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how and where will the

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.
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o publication and/or public presentations.

o Before publication.  
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.
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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.
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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.
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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.
All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters).  
Malignant lymph nodes. To be considered pathologically enlarged and measurable, a lymph node must be >15 mm in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis will be measured and followed. 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.
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6.3.3 methods for evaluation of

All measurements should be taken and recorded in metric notation using a ruler or calipers. All baseline evaluations should be performed as closely as possible to the beginning of treatment and never more than 4 weeks before the beginning of the treatment. The same method of assessment and the same technique should be used to characterize each identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is preferred to evaluation by clinical examination unless the lesion(s) being followed cannot be imaged but are assessable by clinical exam.  
Clinical lesions: Clinical lesions will only be considered measurable when they are superficial
(e.g., skin nodules and palpable lymph nodes) and ≥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 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 FDGPET 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 FDGPET 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.
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6.3.4 response criteria 6.3.4.1 evaluation

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.  
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. 6.3.4.2 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.  
| Target    | Non-Target   | New     | Overall                | Best Overall Response when   |
|-----------|--------------|---------|------------------------|------------------------------|
| Lesions   | Lesions      | Lesions | Response               | Confirmation is Required*    |
| CR        | CR           | No      | CR                     | >4 wks. Confirmation**       |
| CR        | Non              |         |                        |                              |
| CR/Non-PD | No           | PR      | >4 wks. Confirmation** |                              |
| CR        | Not          | No      | PR                     |                              |
| evaluated |              |         |                        |                              |  
| Target                                                                                                                                                                                                                                                                                                                              | Non-Target                                                                                                           | New     | Overall                                           | Best Overall Response when   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------|---------|---------------------------------------------------|------------------------------|
| Lesions                                                                                                                                                                                                                                                                                                                             | Lesions                                                                                                              | Lesions | Response                                          | Confirmation is Required*    |
| PR                                                                                                                                                                                                                                                                                                                                  | Non                                                                                                                      |         |                                                   |                              |
| CR/NonPD/not  evaluated                                                                                                                                                                                                                                                                                                                                     | No                                                                                                                   | PR      |                                                   |                              |
| SD                                                                                                                                                                                                                                                                                                                                  | Non                                                                                                                      |         |                                                   |                              |
| CR/NonPD/not  evaluated                                                                                                                                                                                                                                                                                                                                     | No                                                                                                                   | SD      | Documented at least once >4  wks. from baseline** |                              |
| PD                                                                                                                                                                                                                                                                                                                                  | Any                                                                                                                  | Yes or  | PD                                                |                              |
| No                                                                                                                                                                                                                                                                                                                                  |                                                                                                                      |         |                                                   |                              |
| Any                                                                                                                                                                                                                                                                                                                                 | PD***                                                                                                                | Yes or  | no prior SD, PR or CR                             |                              |
| PD                                                                                                                                                                                                                                                                                                                                  |                                                                                                                      |         |                                                   |                              |
| No                                                                                                                                                                                                                                                                                                                                  |                                                                                                                      |         |                                                   |                              |
| 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. |                                                                                                                      |         |                                                   |                              |  
| 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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for patients with non-measurable disease

| Non-Target Lesions                                                                | New Lesions   | Overall Response   |
|-----------------------------------------------------------------------------------|---------------|--------------------|
| Any                                                                               | Yes           | PD                 |
| * 'Non-CR/non-PD' is preferred over 'stable disease' for non-target disease since |               |                    |  
* '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
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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.
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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.
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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).
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7 nih reporting requirements /

Please refer to definitions provided in Policy 801: Reporting Research Events found here.
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ohsrp office of compliance and

Please refer to the reporting requirements in Policy 801: Reporting Research Events and Policy 802 Non-Compliance Human Subjects Research found here.  
Note: Only IND Safety Reports that meet the definition of an unanticipated problem will need to be reported per these policies.
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7.2.2 irb requirements for pi

Please refer to the reporting requirements in Policy 801: Reporting Research Events found here.
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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.
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nih required data and safety

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.
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8 sponsor safety reporting definitions

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.
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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)
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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.  
- Not Related - There is not a reasonable possibility that the administration of the study product caused the event.
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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.
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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.
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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 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.
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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.
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regulatory reporting for studies conducted

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.
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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.  
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.
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10 statistical considerations statistical hypotheses

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.
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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.
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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, 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.
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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.
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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.)
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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
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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.
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10.4.2 analysis of the primary

1. Safety: see Section **10.4.4**. 2. Recurrence-free survival at 12 months: see Section **10.4.1**.
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10.4.3 analysis of the secondary

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.
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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 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:
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1. for subjects undergoing a

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.
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2. for subjects undergoing a

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%.
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10.4.5 baseline descriptive statistics

Demographic and baseline clinical characteristics of all subjects will be reported.
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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.
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10.4.7 exploratory analyses

The following objectives will be analyzed as indicated for each:
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.
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11 collaborative agreements material transfer

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)
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12 human subjects protections rationale

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 the clinic setting and in the hospital prior to treatment and prior to obtaining a signed informed consent.
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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.
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participation of subjects unable to

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.
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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.
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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 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.
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12.4.2 risks of exposure to

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 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.
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12.4.3 non-physical risks of genetic

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.
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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.
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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
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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.  
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.
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12.5.1 request for waiver of

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.
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13 pharmaceutical and investigational device

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
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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 infusion reaction symptoms.  
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).
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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 |                    |                |                    |
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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. MVT5873 Injection drug product is stored at -20oC.
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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.
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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

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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.  
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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.  
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2(2): p. 219-29.
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15 appendices

| ECOG Performance Status Scale                |                                                                                                                                                                                                                                                |
|----------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Grade                                        | Descriptions                                                                                                                                                                                                                                   |
| Normal activity. Fully active, able to carry |                                                                                                                                                                                                                                                |
| 0                                            | on all pre-disease performance without  restriction. 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). |
| 1                                            | 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.                                                                                  |
| 2                                            | In bed >50% of the time. Capable of only                                                                                                                                                                                                       |
| 3                                            | limited self-care, confined to bed or chair  more than 50% of waking hours. 100% bedridden. Completely disabled.                                                                                                                               |
| 4                                            | Cannot carry on any self-care. Totally  confined to bed or chair.                                                                                                                                                                              |
| 5                                            | Dead.                                                                                                                                                                                                                                          |
normal
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 1 penia Cardiac  2 1 1 disorders Atrial  1 fibrillation Sinus  1 tachycardia Tachycardia 1 1 Ear and  labyrinth  disorders 2 1 Ear  1 congestion Ear  1 discomfort Vertigo 1   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 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  1 disorders Hypothyroidi 1 sm Eye disorders 1 1 1 Lacrimation  1 increased Ocular  1 icterus Vision  1 blurred Gastrointestin 6 5 3 2 1 2 4 1 1 1 6 9 3 1 4 1 6 1 al disorders 2 4 4 Abdominal  1 1 discomfort Abdominal  1 1 distension Abdominal  1 hernia Abdominal  3 2 1 2 1 2 2 1 pain Abdominal  1 pain upper 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  1discomfort   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 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  1 discoloured Flatulence 1 2 Gastrointesti nal  haemorrhage 1 Gingival  1 bleeding 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 3 4 9 4 1 5 1 1 2 4 1 0  1  Asthenia 1 1 1 Chest  1 discomfort 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   |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 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 1 1 s Inflammation 1 Localised  1 oedema Malaise 1 1 2 Mucosal  1 inflammation Oedema  1 1 1 1 3 1 1 peripheral Pain 1 1 1 1 Pyrexia 1 2 1 2 2 1 2 Hepatobiliary  1 1 1 1 disorders Hyperbilirubi 1 1 naemia Jaundice 1 1 Immune  system  disorders 1 1 1 1 Infusion  related  reaction 1 1 1 1 Infections and  1 1 1 1 1 2 1 2 2 2 infestations Candida  1 infection Clostridium  1difficile colitis   |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 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  1 1 infection Nail infection 1 Pneumonia 1 Rhinitis 1 Sinusitis 1 Upper  respiratory  tract infection 1 1 Urinary tract  1 1 1 infection Injury,  poisoning and  procedural  complications 1 2 2 Fall 1 1 Incision site  1 inflammation Wound 1 Wound  1 complication Investigations 5 4 1 6 1 4 1 2 8 1 1 3 4 5 5 1 1 1 8 6 5 5 5 1 0 3 Activated  partial  thromboplast in time  prolonged 1   |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 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 1100   |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 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  1 1 1 increased Lymphocyte  count  decreased 1 1 1 1 Neutrophil  count  decreased 1 1 1 1 Platelet count  1 2 1 1 decreased Weight  1 1 1 1 decreased 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  1 1 1 1 1appetite   |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 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 1 3 1 1 1 1 2 2 2 mia Hyperkalaem 1 1 ia Hypermagnes 1 aemia Hypertriglyce 1 ridaemia Hypoalbumin 1 2 1 1 1 aemia Hypocalcaem 1 1 ia Hypoglycaem 1 ia Hypokalaemi 1 1 1 1 1 a Hypomagnes 2 1 1 aemia Hyponatraem 1 1 1 1 ia Hypophospha 1 taemia Iron  1 deficiency Vitamin B12  1 deficiency Vitamin D  1deficiency   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 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  1 spasms Muscular  1 1 weakness Musculoskele 1 tal discomfort Musculoskele 1 1 1 tal pain Myalgia 1 1 Neck pain 1 1 Pain in  1 1 1 extremity Neoplasms  benign,  malignant and  unspecified  (incl cysts and  polyps) Malignant  neoplasm  progression   |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 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  1 disorder Confusional  1 state Dizziness 1 1 Encephalopat hy Headache 1 1 1 Neuropathy  1 4 1 1 peripheral Paraesthesia 1 Peripheral  sensory  neuropathy 1 1 1 Somnolence 1 Syncope 1 Psychiatric  1 1 1 1 2 2 disorders Depression 1 1 1 Disorientatio 1 n Insomnia 1 2 1 Renal and  urinary  disorders 1 1 1 2 1 Chromaturia 2   |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 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  1 1 1 exertional Epistaxis 1 2 Hiccups 1 1 Nasal  1 1 congestion Paranasal  sinus  discomfort 1 Pleural  1 effusion Pneumonia 1 Pneumonitis 1 Productive  1 1 cough Pulmonary  1 congestion Pulmonary  1embolism   |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| 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 1 1 s Night sweats 1 Pruritus 1 1 1 Pruritus  1 generalised Rash 1 2 Rash maculopapular 1 2 1 Urticaria 1 Surgical and  medical  procedures 1 Wound  1 drainage Vascular  1 1 1 3 1 1 3 1 1 1 disorders Deep vein  1 1 1 thrombosis Flushing 1 1 Hypertension 1 1 1 1 1 Hypotension 1 1 1 1 *Unaudited data as of 15-Dec-2017   |
|---|  
| 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                                                                                                                                                                                                                                                                                                                                                                 | 1     | 1  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| disorders Sinus                                                                                                                                                                                                                                                                                                                                                         | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| tachycardia Tachycardia                                                                                                                                                                                                                                                                                                                                                 | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Eye disorders                                                                                                                                                                                                                                                                                                                                                           | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Ocular icterus                                                                                                                                                                                                                                                                                                                                                          | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Gastrointestin                                                                                                                                                                                                                                                                                                                                                          | 3     | 1  | 3  | 5  | 4  | 3  | 1  | 2  | 1  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| al disorders Abdominal                                                                                                                                                                                                                                                                                                                                                  | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| pain Abdominal                                                                                                                                                                                                                                                                                                                                                          | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| pain upper Constipation                                                                                                                                                                                                                                                                                                                                                 | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Diarrhoea                                                                                                                                                                                                                                                                                                                                                               | 1     | 1  | 1  | 1  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Faeces                                                                                                                                                                                                                                                                                                                                                                  | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| discoloured Nausea                                                                                                                                                                                                                                                                                                                                                      | 1     | 3  | 1  | 1  | 1  | 1  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Oral pain                                                                                                                                                                                                                                                                                                                                                               | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Stomatitis                                                                                                                                                                                                                                                                                                                                                              | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |  
| 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                                                                                                                                                                                                                                                                                                                                                           | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| disorders Hyperbilirubi                                                                                                                                                                                                                                                                                                                                                 | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| naemia Immune  system  disorders                                                                                                                                                                                                                                                                                                                                        | 1     | 1  | 1  | 1  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Infusion  related  reaction                                                                                                                                                                                                                                                                                                                                             | 1     | 1  | 1  | 1  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Infections and                                                                                                                                                                                                                                                                                                                                                          | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| infestations Candida                                                                                                                                                                                                                                                                                                                                                    | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| infection 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  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |  
| 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                                                                                                                                                                                                                                                                                                                                                          | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| phosphatase 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                                                                                                                                                                                                                                                                                                                                                                  | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| increased Lymphocyte  count  decreased                                                                                                                                                                                                                                                                                                                                  | 1     | 1  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Platelet count                                                                                                                                                                                                                                                                                                                                                          | 1     | 1  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| decreased White blood  cell count  decreased                                                                                                                                                                                                                                                                                                                            | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Musculoskelet al and  connective                                                                                                                                                                                                                                                                                                                                        | 1     | 1  | 2  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| 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  |
| tissue  disorders Arthralgia                                                                                                                                                                                                                                                                                                                                            | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Back pain                                                                                                                                                                                                                                                                                                                                                               | 1     | 1  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Neck pain                                                                                                                                                                                                                                                                                                                                                               | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Psychiatric                                                                                                                                                                                                                                                                                                                                                             | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| disorders 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 maculopapular                                                                                                                                                                                                                                                                                                                                                                         | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Urticaria                                                                                                                                                                                                                                                                                                                                                               | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| Vascular                                                                                                                                                                                                                                                                                                                                                                | 1     | 1  | 1  | 1  |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |
| disorders Flushing                                                                                                                                                                                                                                                                                                                                                      | 1     |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |  
| 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                                                                                                                                                                                                                                                                                                                                       |       |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |    |  
| Manufacturing  Ctrl No.         | Subject              | Drug       | Dose            | and            | Cycl                 | Adverse      | Event     | CTCAE Grade   | Relationship   |
|---------------------------------|----------------------|------------|-----------------|----------------|----------------------|--------------|-----------|---------------|----------------|
| ID                              | Frequency            | e          | (Verbatim Term) |                |                      |              |           |               |                |
| 02-004                          | MVT-5873             | 1mg/kg Q2W | 1               | Hypotension    | 3 (severe)           | Unrelated    |           |               |                |
| MVT5873-2016- 001               | 02-004               | MVT-5873   | 1mg/kg Q2W      | 1              | Hyperbilirubinemia   | 3 (severe)   | Unrelated |               |                |
| MVT5873-2016- 002               | 01-012               | MVT-5873   | 1mg/kg Q2W      | 1              | Fever                | 2 (moderate) | Unrelated |               |                |
| MVT5873-2016- 003               | 01-012               | MVT-5873   | 1mg/kg Q2W      | 2              | Encephalopathy       | 5 (death)    | Unrelated |               |                |
| MVT5873-2016- 005               | 02-007               | MVT-5873   | 1mg/kg Q2W      | 4              | Lung Infection*      | 3 (severe)   | Unrelated |               |                |
| MVT5873-2016- 006 MVT5873-2016- | 02-002               | MVT-5873   | 1mg/kg Q2W      | 1              | Clinical Progression | 5 (death)    | Unrelated |               |                |
| 007                             | of Pancreatic Cancer |            |                 |                |                      |              |           |               |                |
| MVT5873-2016-                   | 02-028               | MVT-5873   | 3mg/kg QW       | 1              | Clinical Progression |              |           |               |                |
| 010                             | of                   | Pancreatic |                 |                |                      |              |           |               |                |
| Carcinoma                       | 5 (death)            | Unrelated  |                 |                |                      |              |           |               |                |
| 01-025                          | MVT-5873             | 3mg/kg QW  | 2               | Progression    | of                   |              |           |               |                |
| MVT5873-2016-                   | 5 (death)            | Unrelated  |                 |                |                      |              |           |               |                |
| 011                             | Disease              |            |                 |                |                      |              |           |               |                |
| 02-034                          | MVT-5873             | 3mg/kg QW  | 1               | Lung Infection | 3 (severe)           | Unrelated    |           |               |                |
| MVT5873-2017- 001               | 02-034               | MVT-5873   | 3mg/kg QW       | 1              | Lung Infection       | 3 (severe)   | Unrelated |               |                |
| MVT5873-2017- 002               | 02-006               | MVT-5873   | 3mg/kg Q2W      | 10             | Weakness             | 3 (severe)   | Unrelated |               |                |
| MVT5873-2017- 003               |                      |            |                 |                |                      |              |           |               |                |  
| Manufacturing  Ctrl No.                                                                                                                 | Subject                        | Drug       | Dose            | and                 | Cycl         | Adverse   | Event     | CTCAE Grade   | Relationship   |
|-----------------------------------------------------------------------------------------------------------------------------------------|--------------------------------|------------|-----------------|---------------------|--------------|-----------|-----------|---------------|----------------|
| ID                                                                                                                                      | Frequency                      | e          | (Verbatim Term) |                     |              |           |           |               |                |
| 02-006                                                                                                                                  | MVT-5873                       | 3mg/kg Q2W | 10              | Headache            | 2 (moderate) | Unrelated |           |               |                |
| MVT5873-2017- 005                                                                                                                       | 02-006                         | MVT-5873   | 3mg/kg Q2W      | 10                  | Clinical     | Disease   |           |               |                |
| MVT5873-2017-                                                                                                                           | 5 (death)                      | Unrelated  |                 |                     |              |           |           |               |                |
| 006                                                                                                                                     | Progression                    |            |                 |                     |              |           |           |               |                |
| 01-024                                                                                                                                  | MVT-5873                       | 2mg/kg QW  | 2               | Malignant neoplasm  |              |           |           |               |                |
| MVT5873-2017-                                                                                                                           | 5 (death)                      | Unrelated  |                 |                     |              |           |           |               |                |
| 009                                                                                                                                     | progression                    |            |                 |                     |              |           |           |               |                |
| 03-014                                                                                                                                  | MVT-5873                       | 1mg/kg QW  | 2               | Disease Progression | 5 (death)    | Unrelated |           |               |                |
| MVT5873-2017- 010                                                                                                                       | 01-047                         | MVT-5873   | 1mg/kg QW       | 3                   | Fever        | 1 (mild)  | Unrelated |               |                |
| MVT5873-2017- 012 MVT5873-2017-                                                                                                         | 03-046                         | MVT-5873   | 1mg/kg Q2W      | 5                   | Upper        |           |           |               |                |
| 013                                                                                                                                     | Gastrointestinal  Hemorrhage** | 3 (severe) | Unrelated       |                     |              |           |           |               |                |
| 02-016                                                                                                                                  | MVT-5873                       | 1mg/kg QW  | 13              | Gastrointestinal    |              |           |           |               |                |
| MVT5873-2017-                                                                                                                           | 3 (severe)                     | Unrelated  |                 |                     |              |           |           |               |                |
| 014                                                                                                                                     | Bleeding***                    |            |                 |                     |              |           |           |               |                |
| 02-016                                                                                                                                  | MVT-5873                       | 1mg/kg QW  | 13              | Vomiting***         | 3 (severe)   | Unrelated |           |               |                |
| MVT5873-2017- 015 *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 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
normal
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)