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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03118349
Recruitment Status : Active, not recruiting
First Posted : April 18, 2017
Last Update Posted : March 2, 2020
Sponsor:
Information provided by (Responsible Party):
BioNTech SE ( BioNTech Research & Development, Inc. )

Brief Summary:
Open label, nonrandomized, dose-escalation with cohort expansion trial of MVT-5873/MVT-1075 in subjects with previously treated, CA19-9 positive malignancies (e.g., pancreatic adenocarcinoma).

Condition or disease Intervention/treatment Phase
Pancreatic Carcinoma Tumors That Express CA 19-9 Drug: MVT-1075 Drug: MVT-5873 Phase 1

Detailed Description:

Open label, nonrandomized, dose escalation trial of MVT-5873/MVT-1075 to evaluate safety, dosimetry, determine the MTD and recommended phase 2 dose, and define the pharmacokinetics of MVT-1075. The population consists of subjects with CA19-9 positive malignancies (i.e., predominately pancreatic adenocarcinoma) who may benefit from a CA19-9-based radioimmunotherapy.

The study will utilize a 3+3 study design to identify the MTD. The RP2D will be no higher than the MTD. An expansion group will receive MVT-5873/MVT-1075 at the RP2D in order to obtain initial estimates of response and additional information on safety.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I, Open-Label, Multi-Center, Dose Escalation With Expansion Trial of 177Lu Human Monoclonal Antibody 5B1 (MVT-1075) in Combination With a Blocking Dose of MVT-5873 as Radioimmunotherapy in Relapse/Refractory Subjects With Pancreatic Cancer or Other CA19-9 Positive Malignancies
Actual Study Start Date : June 1, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Escalation Cohorts
MVT-5873 blocking dose and MVT-1075 dose escalation Initial to maximum tolerated dose
Drug: MVT-1075
MVT-1075 is administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.
Other Name: 177Lu-CHX-A"-DTPA-HuMab-5B1

Drug: MVT-5873
MVT-5873 is administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.
Other Name: HuMab-5B1

Experimental: Expansion Cohort
MVT-5873 blocking dose and MVT-1075 Maximum tolerated dose
Drug: MVT-1075
MVT-1075 is administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.
Other Name: 177Lu-CHX-A"-DTPA-HuMab-5B1

Drug: MVT-5873
MVT-5873 is administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.
Other Name: HuMab-5B1




Primary Outcome Measures :
  1. The MTD of MVT-5873/MVT-1075 [ Time Frame: Through study completion. Estimated at one year ]
    The MTD of MVT-5873/MVT-1075 is the highest dose of MVT-1075 at which fewer than 33% subjects experience a dose limiting toxicity

  2. Occurrence of graded AEs in each subject [ Time Frame: Through study completion. Estimated at one year ]
    Occurrence of graded AEs in each subject


Secondary Outcome Measures :
  1. Specific organ distribution of MVT-1075 as assessed with planar gamma camera [ Time Frame: Through study completion. Estimated at one year ]
    Specific organ distribution of MVT-1075 as assessed with planar gamma camera

  2. Specific organ distribution of MVT-1075 as assessed with SPECT imaging [ Time Frame: Through study completion. Estimated at one year ]
    Specific organ distribution of MVT-1075 as assessed with SPECT imaging

  3. A recommended phase 2 dose (RP2D) of MVT-5873/MVT-1075 [ Time Frame: Through study completion. Estimated at one year. ]

    Previously determined MTD Overall assessment of safety as determined by Safety Committee

    Overall assessment of safety as determined by Safety Committee


  4. Evaluate the tumor response rate to MVT-5873/MVT-1075 at the RP2D [ Time Frame: Through study completion. Estimated at one year. ]
    Response categories as assessed by RECIST v1.1

  5. Evaluate duration of response [ Time Frame: Through study completion. Estimated at one year. ]
    Time from first onset of response to progression or death

  6. Evaluate the relationship between circulating CA19-9 levels and tumor response [ Time Frame: Through study completion. Estimated at one year. ]
    periodic assessment of CA19-9 expression

  7. Evaluate the relationship between circulating CA19-9 levels and MVT-1075 pharmacokinetics [ Time Frame: Through study completion. Estimated at one year. ]
    periodic assessments pre and post MVT-1075

  8. Evaluate formation of anti-drug antibodies (ADA) [ Time Frame: On Day 1, Day 15 and End of Treatment Visit only of each cycle for up to 4 cycles. (each cycle is 57 days) ]
    Presence or absence of anti-drug antibodies (ADA) as assessed by assay to be developed

  9. Cmax [ Time Frame: 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). ]
    The peak plasma concentration of the drug after administration

  10. Cmin [ Time Frame: 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). ]
    measure the lowest concentration that the drug reaches before the next dose is administered.

  11. Tmax [ Time Frame: 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). ]
    Time to reach the study drug

  12. Vd [ Time Frame: 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). ]
    Volume of distribution

  13. t1/2 [ Time Frame: 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). ]
    Half-life of Elimination

  14. AUC [ Time Frame: 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). ]
    Area under the plasma concentration time curve

  15. Cl [ Time Frame: 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). ]
    Clearance of study drug



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 IHC performed on tumor samples or elevated serum levels (≥1.5 x ULN) of CA19-9 considered secondary to tumor
  6. Evaluable or measurable disease based on RECIST 1.1 (50)
  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 Table 2
  9. ECOG performance status of 0 or 1 (51), or KPS of 100% to 80% (52)
  10. Adequate hematologic, renal and hepatic laboratory parameters

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 (2) years
  4. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
  5. 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
  6. Major surgery other than diagnostic surgery within 28 days of Study Day 1
  7. History of anaphylactic reaction to human, or humanized, antibody
  8. Pregnant or currently breast-feeding
  9. Known to be positive for HIV, Hepatitis B, or Hepatitis C
  10. Psychiatric illness/social situations that would interfere with compliance with study requirements
  11. Significant cardiovascular risk including, but not limited to, recent (within 4 weeks) coronary stenting or myocardial infarction within 6 months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03118349


Locations
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United States, Arizona
HonorHealth Research Institute
Scottsdale, Arizona, United States, 85258
United States, New York
MSKCC
New York, New York, United States, 10065
Sponsors and Collaborators
BioNTech Research & Development, Inc.
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Responsible Party: BioNTech Research & Development, Inc.
ClinicalTrials.gov Identifier: NCT03118349    
Other Study ID Numbers: MV-0916-CP-001.01
First Posted: April 18, 2017    Key Record Dates
Last Update Posted: March 2, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BioNTech SE ( BioNTech Research & Development, Inc. ):
CA19-9 Positive Malignancies
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases