Clinical trial NCT02687230: Phase 1 Imaging Study of 89Zr-DFO-HuMab-5B1 With HuMab-5B1
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pancreatic Carcinoma
Tumors That Express CA19-9
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
Collaborators: name: SciQuus Oncology
First posted: 2016-02-22
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety of MVT-2163 alone and in combination with MVT-5873
timeFrame: About 12 months
measure: Peak Plasma Concentration (Cmax) of MVT-2163 alone and in combination with MVT-5873
timeFrame: About 12 months
measure: Biodistribution of MVT-2163 alone and in combination with MVT-5873
timeFrame: About 12 months
measure: Dose of MVT-5873 required for optimal tumor visualization when combined with a fixed dose of MVT-2163
timeFrame: About 12 months
measure: Determine the optimal time interval between MVT-2163 dose administration and tumor PET imaging
timeFrame: About 12 months
measure: Area under the plasma concentration versus time curve (AUC) of MVT-2163 alone and in combination with MVT-5873
timeFrame: About 12 months
measure: Half-life (T1/2) of MVT-2163 alone and in combination with MVT-5873
timeFrame: About 12 months
Secondary outcomes:
measure: The ability of MVT-2163 to detect sites of disease (localized and metastatic) in pancreatic cancer and/or other CA19-9 positive malignancies
timeFrame: About 12 months
measure: Radiation dosimetry estimates using quantitative MVT-2163 biodistribution uptake data
timeFrame: About 12 months
measure: MVT-2163 PET imaging results in comparison with varying levels of CA19-9 antigen expression by IHC
timeFrame: About 12 months
measure: MVT-2163 PET imaging results in comparison with circulating CA19-9 levels
timeFrame: About 12 months
measure: Presence of anti-drug antibodies (ADA) using an MVT-5873 ADA assay
timeFrame: About 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: BioNTech SE
name: BioNTech Responsible Person
role: STUDY_DIRECTOR
References:
citation: Tully KM, Tendler S, Carter LM, Sharma SK, Samuels ZV, Mandleywala K, Korsen JA, Delos Reyes AM, Piersigilli A, Travis WD, Sen T, Pillarsetty N, Poirier JT, Rudin CM, Lewis JS. Radioimmunotherapy Targeting Delta-like Ligand 3 in Small Cell Lung Cancer Exhibits Antitumor Efficacy with Low Toxicity. Clin Cancer Res. 2022 Apr 1;28(7):1391-1401. doi: 10.1158/1078-0432.CCR-21-1533.