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Clinical Trial Record

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Study of 177Lu Human Monoclonal Antibody 5B1 (MVT-1075) in Combination With a Blocking Dose of MVT-5873 as Radioimmunotherapy

2017-06-01

2018-04-11

2018-04-11

4

Study Overview

Study of 177Lu Human Monoclonal Antibody 5B1 (MVT-1075) in Combination With a Blocking Dose of MVT-5873 as Radioimmunotherapy

Open label, nonrandomized, dose-escalation with cohort expansion study of MVT-5873/MVT-1075 in subjects with previously treated, Carbohydrate Antigen 19-9 (CA19-9) positive malignancies (e.g., pancreatic adenocarcinoma).

Open label, nonrandomized, dose escalation study of MVT-5873/MVT-1075 to evaluate safety, dosimetry, determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), and define the pharmacokinetics of MVT-1075. The population consisted of subjects with CA19-9 positive malignancies (i.e., predominately pancreatic adenocarcinoma) who may benefit from a CA19-9-based radioimmunotherapy. The study utilized a 3+3 study design to identify the MTD. The RP2D was planned to be no higher than the MTD. An expansion group was planned to receive MVT-5873/MVT-1075 at the RP2D in order to obtain initial estimates of response and additional information on safety.

  • Pancreatic Carcinoma
  • Tumors That Express CA 19-9
  • DRUG: MVT-1075
  • DRUG: MVT-5873
  • MV-0916-CP-001.01

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates Results Reporting Dates Study Record Updates

2017-03-23  

N/A  

2023-04-19  

2017-04-13  

N/A  

2023-04-21  

2017-04-18  

N/A  

2023-04  

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Escalation Cohorts

MVT-5873 blocking dose and MVT-1075 dose escalation; Initial to maximum tolerated dose

DRUG: MVT-1075

  • MVT-1075 administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.

DRUG: MVT-5873

  • MVT-5873 administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.
EXPERIMENTAL: Expansion Cohort - no subjects enrolled

MVT-5873 blocking dose and MVT-1075 Maximum tolerated dose

DRUG: MVT-1075

  • MVT-1075 administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.

DRUG: MVT-5873

  • MVT-5873 administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.
Primary Outcome MeasuresMeasure DescriptionTime Frame
The MTD of MVT-5873/MVT-1075The MTD of MVT-5873/MVT-1075 is the highest dose of MVT-1075 at which fewer than 33% subjects experience a dose limiting toxicityThrough study completion. Estimated at one year
Occurrence of graded adverse events (AEs) in each subjectOccurrence of graded AEs in each subjectThrough study completion. Estimated at one year
Secondary Outcome MeasuresMeasure DescriptionTime Frame
Specific organ distribution of MVT-1075 as assessed with planar gamma cameraSpecific organ distribution of MVT-1075 as assessed with planar gamma cameraThrough study completion. Estimated at one year
Specific organ distribution of MVT-1075 as assessed with single-photon emission computed tomography (SPECT) imagingSpecific organ distribution of MVT-1075 as assessed with SPECT imagingThrough study completion. Estimated at one year
A RP2D of MVT-5873/MVT-1075Previously determined MTD; Overall assessment of safety as determined by Safety CommitteeThrough study completion. Estimated at one year.
Evaluate the tumor response rate to MVT-5873/MVT-1075 at the RP2DResponse categories as assessed by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)Through study completion. Estimated at one year.
Evaluate duration of response of MVT-5873/MVT-1075Time from first onset of response to progression or deathThrough study completion. Estimated at one year.
Evaluate formation of anti-drug antibodies (ADA)Presence or absence of ADA as assessed by assay to be developedOn Day 1, Day 15 and End of Treatment Visit only of each cycle for up to 4 cycles. (each cycle is 57 days)
CmaxThe peak plasma concentration of the drug after administrationMeasured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
CminMeasure the lowest concentration that the drug reaches before the next dose is administered.Measured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
TmaxTime to reach the study drugMeasured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
VdVolume of distributionMeasured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
t1/2Half-life of EliminationMeasured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
AUCArea under the plasma concentration time curveMeasured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).
ClClearance of study drugMeasured on Day 1 Prior to MVT-1075 dose and again 15 min. 30 min. 60 min. 120 min. post MVT-1075 dose. On Day 3, Day 8, Day 15 Prior and 15 min Post MVT-1075 dose. Anytime on Day 22 and Day 29. During cycle 1 and 2 only (each cycle is 57 days).

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

    Inclusion Criteria:
    1. Signed, informed consent 2. Age 18 or more years 3. Histologically or cytologically confirmed, previously treated, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other CA19-9 positive malignancies 4. Prior treatment with (or intolerance to) at least one standard systemic regimen for the patient's respective tumor 5. Evidence of tumor expression of CA19-9 based on immunohistochemistry performed on tumor samples or elevated serum levels (≥1.5 x upper limits of normal [ULN]) of CA19-9 considered secondary to tumor 6. Evaluable or measurable disease based on RECIST 1.1 7. Recovered from any prior treatment related toxicity to at least Grade 1 with exception of Grade 2 alopecia or other Grade 2 toxicity with prior approval of the Medical Monitor 8. If previously exposed to irradiation, the combined prior and anticipated exposure for Cycle 1 is not expected to exceed organ exposure limits outlined in the study protocol 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or Karnofsky performance status (KPS) of 100% to 80% 10. Adequate hematologic, renal and hepatic laboratory parameters 11. Willingness to participate in collection of pharmacokinetic samples 12. Willingness to use adequate contraception throughout study and for a period of 3 months after last dose of MVT-5873 or MVT-1075 (whichever is later)
    Exclusion Criteria:
    1. Brain metastases unless previously treated and well controlled for at least 3 months 2. Any tumor mass greater than 10 cm in longest diameter 3. Other known active cancer(s) likely to require treatment in the next two years 4. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy 5. Prior radiation therapy encompassing more than 25% of the skeleton or prior treatment with 89Strontium or 153Samarium 6. Fewer than 28 days from prior anticancer therapy including chemotherapy, hormonal, investigational, and/or biological therapies and irradiation except for:
    1. Ongoing hormonal therapy administered for control of cancer (e.g., breast cancer, prostate cancer), which may be continued throughout the study 2. MVT-5873 and MVT-2163 administered as part of a different protocol 7. Major surgery other than diagnostic surgery within 28 days of Study Day 1 8. History of anaphylactic reaction to human, or humanized, antibody 9. Pregnant or currently breast-feeding 10. Known to be positive for human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C 11. Psychiatric illness/social situations that would interfere with compliance with study requirements 12. Significant cardiovascular risk including, but not limited to, recent (within 4 weeks) coronary stenting or myocardial infarction within 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

    • STUDY_DIRECTOR: BioNTech Responsible Person, BioNTech SE

    Publications

    The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

    General Publications

    • 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.
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