Clinical Trials /

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

NCT03118349

Description:

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).

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MV-0916-CP-001.01
  • NCT ID: NCT03118349

Conditions

  • Pancreatic Carcinoma
  • Tumors That Express CA 19-9

Interventions

DrugSynonymsArms
MVT-1075177Lu-CHX-A"-DTPA-HuMab-5B1Escalation Cohorts
MVT-5873HuMab-5B1Escalation Cohorts

Purpose

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
Escalation CohortsExperimentalMVT-5873 blocking dose and MVT-1075 dose escalation Initial to maximum tolerated dose
  • MVT-1075
  • MVT-5873
Expansion CohortExperimentalMVT-5873 blocking dose and MVT-1075 Maximum tolerated dose
  • MVT-1075
  • MVT-5873

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The MTD of MVT-5873/MVT-1075
Time Frame:Through study completion. Estimated at one year
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Specific organ distribution of MVT-1075 as assessed with planar gamma camera
Time Frame:Through study completion. Estimated at one year
Safety Issue:
Description:Specific organ distribution of MVT-1075 as assessed with planar gamma camera
Measure:Specific organ distribution of MVT-1075 as assessed with SPECT imaging
Time Frame:Through study completion. Estimated at one year
Safety Issue:
Description:Specific organ distribution of MVT-1075 as assessed with SPECT imaging
Measure:A recommended phase 2 dose (RP2D) of MVT-5873/MVT-1075
Time Frame:Through study completion. Estimated at one year.
Safety Issue:
Description:Previously determined MTD Overall assessment of safety as determined by Safety Committee Overall assessment of safety as determined by Safety Committee
Measure:Evaluate the tumor response rate to MVT-5873/MVT-1075 at the RP2D
Time Frame:Through study completion. Estimated at one year.
Safety Issue:
Description:Response categories as assessed by RECIST v1.1
Measure:Evaluate duration of response
Time Frame:Through study completion. Estimated at one year.
Safety Issue:
Description:Time from first onset of response to progression or death
Measure:Evaluate the relationship between circulating CA19-9 levels and tumor response
Time Frame:Through study completion. Estimated at one year.
Safety Issue:
Description:periodic assessment of CA19-9 expression
Measure:Evaluate the relationship between circulating CA19-9 levels and MVT-1075 pharmacokinetics
Time Frame:Through study completion. Estimated at one year.
Safety Issue:
Description:periodic assessments pre and post MVT-1075
Measure: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)
Safety Issue:
Description:Presence or absence of anti-drug antibodies (ADA) as assessed by assay to be developed
Measure: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).
Safety Issue:
Description:The peak plasma concentration of the drug after administration
Measure: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).
Safety Issue:
Description:measure the lowest concentration that the drug reaches before the next dose is administered.
Measure: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).
Safety Issue:
Description:Time to reach the study drug
Measure: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).
Safety Issue:
Description:Volume of distribution
Measure: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).
Safety Issue:
Description:Half-life of Elimination
Measure: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).
Safety Issue:
Description:Area under the plasma concentration time curve
Measure: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).
Safety Issue:
Description:Clearance of study drug

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MabVax Therapeutics, Inc.

Trial Keywords

  • CA19-9 Positive Malignancies

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