Study of 177Lu Human Monoclonal Antibody 5B1 (MVT-1075) in Combination With a Blocking Dose of MVT-5873 as Radioimmunotherapy
Study Details
Study Description
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 |
|---|---|---|
| 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.
Study Design
Arms and Interventions
| 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 Names:
Drug: MVT-5873
MVT-5873 is administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.
Other Names:
|
| 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 Names:
Drug: MVT-5873
MVT-5873 is administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The MTD of MVT-5873/MVT-1075 [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
- Occurrence of graded AEs in each subject [Through study completion. Estimated at one year]
Occurrence of graded AEs in each subject
Secondary Outcome Measures
- Specific organ distribution of MVT-1075 as assessed with planar gamma camera [Through study completion. Estimated at one year]
Specific organ distribution of MVT-1075 as assessed with planar gamma camera
- Specific organ distribution of MVT-1075 as assessed with SPECT imaging [Through study completion. Estimated at one year]
Specific organ distribution of MVT-1075 as assessed with SPECT imaging
- A recommended phase 2 dose (RP2D) of MVT-5873/MVT-1075 [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
- Evaluate the tumor response rate to MVT-5873/MVT-1075 at the RP2D [Through study completion. Estimated at one year.]
Response categories as assessed by RECIST v1.1
- Evaluate duration of response [Through study completion. Estimated at one year.]
Time from first onset of response to progression or death
- Evaluate the relationship between circulating CA19-9 levels and tumor response [Through study completion. Estimated at one year.]
periodic assessment of CA19-9 expression
- Evaluate the relationship between circulating CA19-9 levels and MVT-1075 pharmacokinetics [Through study completion. Estimated at one year.]
periodic assessments pre and post MVT-1075
- Evaluate formation of anti-drug antibodies (ADA) [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
- Cmax [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
- Cmin [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.
- Tmax [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
- Vd [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
- t1/2 [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
- AUC [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
- Cl [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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signed, informed consent
-
Age 18 or more years
-
Histologically or cytologically confirmed, previously treated, locally-advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) or other CA19-9 positive malignancies
-
Prior treatment with (or intolerance to) at least one standard systemic regimen for the patient's respective tumor
-
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
-
Evaluable or measurable disease based on RECIST 1.1 (50)
-
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
-
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
-
ECOG performance status of 0 or 1 (51), or KPS of 100% to 80% (52)
-
Adequate hematologic, renal and hepatic laboratory parameters
Exclusion Criteria:
-
Brain metastases unless previously treated and well controlled for at least 3 months
-
Any tumor mass greater than 10 cm in longest diameter
-
Other known active cancer(s) likely to require treatment in the next two (2) years
-
Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
-
Fewer than 28 days from prior anticancer therapy including chemotherapy, hormonal, investigational, and/or biological therapies and irradiation except for:
-
Ongoing hormonal therapy administered for control of cancer (e.g., breast cancer, prostate cancer), which may be continued throughout the study
-
MVT-5873 and MVT-2163 administered as part of a different protocol
-
Major surgery other than diagnostic surgery within 28 days of Study Day 1
-
History of anaphylactic reaction to human, or humanized, antibody
-
Pregnant or currently breast-feeding
-
Known to be positive for HIV, Hepatitis B, or Hepatitis C
-
Psychiatric illness/social situations that would interfere with compliance with study requirements
-
Significant cardiovascular risk including, but not limited to, recent (within 4 weeks) coronary stenting or myocardial infarction within 6 months
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | HonorHealth Research Institute | Scottsdale | Arizona | United States | 85258 |
| 2 | MSKCC | New York | New York | United States | 10065 |
Sponsors and Collaborators
- BioNTech Research & Development, Inc.
Investigators
- Study Director: BioNTech Responsible Person, BioNTech SE
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MV-0916-CP-001.01