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).
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
Drug | Synonyms | Arms |
---|
MVT-1075 | 177Lu-CHX-A"-DTPA-HuMab-5B1 | Escalation Cohorts |
MVT-5873 | HuMab-5B1 | Escalation 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
Name | Type | Description | Interventions |
---|
Escalation Cohorts | Experimental | MVT-5873 blocking dose and MVT-1075 dose escalation Initial to maximum tolerated dose | |
Expansion Cohort | Experimental | MVT-5873 blocking dose and MVT-1075 Maximum tolerated dose | |
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: | Suspended |
Lead Sponsor: | BioNTech Research & Development, Inc. |
Trial Keywords
- CA19-9 Positive Malignancies
Last Updated
April 19, 2021