Pancreatic Carcinoma, Tumors That Express CA 19-9
Conditions
Keywords
CA19-9 Positive Malignancies
Brief summary
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).
Detailed description
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.
Interventions
DRUGMVT-1075
MVT-1075 administered in two fractions, with each administration of MVT-1075 preceded by blocking dose of MVT-5873.
DRUGMVT-5873
MVT-5873 administered intravenously as a non-radioactive blocking agent prior to administration of MVT-1075.
Sponsors
BioNTech Research & Development, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of graded adverse events (AEs) in each subject | Through study completion. Estimated at one year | Occurrence of graded AEs in each subject |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| A 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 |
| 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 |
| 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 Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) |
| Evaluate duration of response of MVT-5873/MVT-1075 | Through study completion. Estimated at one year. | Time from first onset of response to progression or death |
| 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 ADA as assessed by assay to be developed |
| 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 |
| 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 |
| Specific organ distribution of MVT-1075 as assessed with single-photon emission computed tomography (SPECT) imaging | Through study completion. Estimated at one year | Specific organ distribution of MVT-1075 as assessed with SPECT imaging |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed