Phase 1 Imaging Study of 89Zr-DFO-HuMab-5B1 With HuMab-5B1

Study Overview
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Brief Summary
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Open label, nonrandomized, dose-escalation trial of MVT-2163 and MVT-5873 used in performing PET scans. The study is designed to determine the best time and dose of these agents that result in the best PET image of a tumor. Subjects will be seen on days 1, 2, 4, and 7 for imaging and a clinical assessment. The last study visit is on day 28.

Detailed Description
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This is an open label, nonrandomized, dose-escalation trial of a fixed dose of MVT-2163 and varying antibody masses of MVT-5873. The study is designed to identify an optimal dose (total antibody mass) and optimal timing, for tumor imaging using PET scanning. This trial will include a dose escalation and an expansion phase. During the dose escalation portion of the study, a determination of the optimal time to perform PET imaging will be made. Following the identification of the optimal dose and timing, an 10 additional subjects will be imaged using the best dose and timing. In each portion of the study subjects will have a screening visit and, no more than 28 days later, those who are eligible for the study will receive MVT-2163. Each cohort will have 3-6 subjects. Subjects in cohort 1 will be administered MVT-2163 alone on day 1. Subjects in cohorts 2 and 3 will receive MVT-5873 on day 1, followed approximately 10 minutes later by MVT-2163. Subjects will return for visits to the clinic on days 2, 4, and 7 for additional imaging and safety assessments. A follow-up visit will occur on day 28. The study will also evaluate the tissue distribution and pharmacokinetics of MVT-2163 and, based on these data, the study will estimate the radiation dosimetry of MVT-2163. Safety assessments will be performed using ECGs, vital signs measurements, assessments of performance status, and clinical laboratory measurements.

Official Title
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Phase 1 Study of 89Zr-DFO-HuMab-5B1 (MVT-2163) With HuMab-5B1 (MVT-5873) in Patients With Pancreatic Cancer or Other CA19-9 Positive Malignancies

Conditions
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Pancreatic Carcinoma, Tumors That Express CA19-9

Intervention / Treatment
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* Drug: MVT-2163
* Drug: MVT-5873


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed, informed consent Histologically confirmed, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other malignancies known to express CA19-9 positive malignancies At least one lesion by CT or MRI ≥ 2 cm ECOG performance status of 0 to 2 Absolute neutrophil count ≥1.50 x 109/L Hemoglobin ≥ 9.0 g/dL (in the absence of red blood cell transfusions in the prior 14 days) Platelet count >75,000/ mm3 AST/SGOT, ALT/SGPT ≤2.5 x ULN, unless liver metastases are clearly present, then ≤5.0 x ULN Total bilirubin <1.5x the upper limit of normal unless considered due to Gilbert's syndrome in which case, <3x the upper limit of normal Serum creatinine (serum or plasma) ≤ 1.5 x ULN or GFR>50 mL/min Serum albumin > 3.0g/dL Willingness to participate in collection of pharmacokinetic samples Willingness to use adequate contraception throughout study and for a period of 90 days last dose of study drug Exclusion Criteria: Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy Major surgery other than diagnostic surgery within 28 days History of anaphylactic reaction to human, or humanized, antibody Other on-going cancer therapy or investigational agents (except MVT-5873 ) Known history of HIV or Hepatitis C Pregnant or currently breast-feeding Psychiatric illness/social situations that would interfere with compliance with study requirements Significant cardiovascular risk including, but not limited to, recent (within 28 days) coronary stenting or myocardial infarction within 6 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Subjects receive 3 mg of MVT-2163 without the addition of prior MVT-5873. | Drug: MVT-2163<br>* MVT-2163 is administered intravenously as a PET imaging agent<br>* Other names: 89Zr-DFO-HuMab-5B1;|
| Experimental: Cohort 2<br>Subjects receive 17 mg of MVT-5873 followed by 3 mg of MVT-2163. | Drug: MVT-2163<br>* MVT-2163 is administered intravenously as a PET imaging agent<br>* Other names: 89Zr-DFO-HuMab-5B1;Drug: MVT-5873<br>* MVT-5873 is administered intravenously as a non-radioactive blocking agent prior to administration of MVT-2163<br>* Other names: HuMab-5B1;|
| Experimental: Cohort 3<br>Subjects receive 47 mg of MVT-5873 followed by 3 mg of MVT-2163. | Drug: MVT-2163<br>* MVT-2163 is administered intravenously as a PET imaging agent<br>* Other names: 89Zr-DFO-HuMab-5B1;Drug: MVT-5873<br>* MVT-5873 is administered intravenously as a non-radioactive blocking agent prior to administration of MVT-2163<br>* Other names: HuMab-5B1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of MVT-2163 alone and in combination with MVT-5873 | Number of subjects with treatment-related adverse events as assessed by CTCAE v4.0 will be collected and compiled | About 12 months | 
| Peak Plasma Concentration (Cmax) of MVT-2163 alone and in combination with MVT-5873 | Cmax of MVT-2163 | About 12 months | 
| Biodistribution of MVT-2163 alone and in combination with MVT-5873 | The biodistribution of MVT-2163 will be determined by measuring radiation exposure for key organs and tissues | About 12 months | 
| Dose of MVT-5873 required for optimal tumor visualization when combined with a fixed dose of MVT-2163 | Three doses of MVT-5873 (0, 17, and 47 mg) will be combined with MVT-2163 in order to determine which dose results in the best PET imaging of tumor | About 12 months | 
| Determine the optimal time interval between MVT-2163 dose administration and tumor PET imaging | Images will be taken on several days over the first week to determine the optimal day for obtaining PET images | About 12 months | 
| Area under the plasma concentration versus time curve (AUC) of MVT-2163 alone and in combination with MVT-5873 | AUC of MVT-2163 | About 12 months | 
| Half-life (T1/2) of MVT-2163 alone and in combination with MVT-5873 | Half-life (T1/2) of MVT-2163 | About 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ability of MVT-2163 to detect sites of disease (localized and metastatic) in pancreatic cancer and/or other CA19-9 positive malignancies | PET scans obtained with MVT-2163 will be compared with conventional imaging (CT/MRI) to determine if MVT-2163 based PET scans are capable of detection tumors seen with conventional methods | About 12 months | 
| Radiation dosimetry estimates using quantitative MVT-2163 biodistribution uptake data | Bio-distribution data will be used to estimate the radiation exposure of key organs and tissues | About 12 months | 
| MVT-2163 PET imaging results in comparison with varying levels of CA19-9 antigen expression by IHC | A determination will be made as to the effect of varying levels of CA19-9 antigen expression by tumor IHC on the quality of MVT-2163 PET imaging | About 12 months | 
| MVT-2163 PET imaging results in comparison with circulating CA19-9 levels | A determination will be made as to the effect of circulating levels of CA19-9 on the quality of MVT-2163 PET imaging | About 12 months | 
| Presence of anti-drug antibodies (ADA) using an MVT-5873 ADA assay | Subjects will be tested for the development of anti-drug antibodies (ADA) against MVT-5873 | About 12 months |