Description:
Phase 1 Safety and Tolerability Study in Subjects with Pancreatic Cancer or Other CA19-9
Positive Malignancies.
Title
- Brief Title: Study of HuMab-5B1 (MVT-5873) in Subjects With Pancreatic Cancer or Other Cancer Antigen 19-9 (CA19-9) Positive Malignancies
- Official Title: Phase 1 Safety and Tolerability Study of Human Monoclonal Antibody 5B1 (MVT-5873) With Expansion in Subjects With Pancreatic Cancer or Other CA19-9 Positive Malignancies
Clinical Trial IDs
- ORG STUDY ID:
MV-0715-CP-001.01
- NCT ID:
NCT02672917
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| MVT-5873 | HuMab-5B1 | Group C |
| modified FOLFIRINOX (mFOLFIRINOX) | | Group E |
Purpose
Phase 1 Safety and Tolerability Study in Subjects with Pancreatic Cancer or Other CA19-9
Positive Malignancies.
Detailed Description
Open label, multicenter, non-randomized, dose escalation/expansion trial of MVT-5873 as a
single agent and in combination with modified FOLFIRINOX (mFOLFIRINOX) in subjects with
pancreatic and other CA19-9 positive malignancies. The study will define a Maximum Tolerated
Dose (MTD) of MVT-5873 for a Q2 week schedule (Group D), an MTD of MVT-5873 for a Q4 week
schedule (Group C), and an MTD for a Q2 week schedule of MVT-5873 in combination with
mFOLFIRINOX (Group E). Each group will utilize a conventional 3+3 study design to identify
the MTD and recommended phase 2 dose (RP2D).
Following the definition of an MTD in each group, the RP2D of MVT-5873 as a single agent and
in combination with mFOLFIRINOX will be defined. Following the completion of the dose
escalation phase for each group, an expansion group of up to 30 additional subjects will be
treated at the RP2D for each group. In Group D, subjects will be subdivided into two groups
of up to 15 subjects: subjects without peripheral blood expression of CA19-9 and subjects
with peripheral blood expression of CA19-9. MVT-5873 pharmacokinetics (PK) and
pharmacodynamics (PD) will be determined in each group.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Group C | Experimental | MVT-5873 is administered in Group C every 4 weeks by intravenous infusion. Each cycle is 28 days. During dose escalation, doses of MVT-5873 will be increased to define the MTD. Up to 30 patients will be treated at the RP2D. | |
| Group D | Experimental | MVT-5873 is administered in Group D every 2 weeks by intravenous infusion. During dose escalation, doses of MVT-5873 will be increased to defined he MTD. Up to 30 patients will be treated at the RP2D. | |
| Group E | Experimental | MVT-5873 is administered in combination with mFOLFIRINOX every 2 weeks. Both MVT-5873 and mFOLFIRINOX will be administered by intravenous infusion. During dose escalation, doses of MVT-5873, will be increased to define the MTD in combination with mFOLFIRINOX. mFOLFIRINOX will be administered according to institutional standards in compliance with the package insert for each drug. Up to 30 patients will be treated at the RP2D. | - MVT-5873
- modified FOLFIRINOX (mFOLFIRINOX)
|
Eligibility Criteria
Inclusion Criteria
- Signed, informed consent
- Age 18 or more years
- Histologically or cytologically confirmed, locally-advanced or metastatic pancreatic
ductal adenocarcinoma (PDAC) or other CA19-9 positive malignancies
- Recovered from prior treatment related toxicity to at least Grade 1 with exception of
Grade 2 alopecia or other Grade 2 toxicity with approval of the Medical Monitor
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 or KPS of 100%
to 80%
- Adequate hematologic, hepatic, and renal function
- Willingness to participate in collection of pharmacokinetic samples
- Willingness to use adequate contraception throughout study and for a period of 3
months after last dose of MVT-5873
[Group C and Group D Dose Escalation]
- Evaluable or measurable disease based on RECISTv1.1
- Serum CA19-9 levels ≤ 4000 U/mL
[Group C and D]
- Progression following treatment with standard of care for the subject's specific tumor
type
[Group C and D Expansion and Group E Escalation and Expansion]
- Measurable disease based on RECISTv1.1
[Group C and D Expansion, non-PDAC malignancies]
- If negative serum CA19-9 levels (defined as < 1 U/mL or below the level of detection
for institutional test used), subject must have confirmation of CA19-9 expression in
their tumor prior to study entry
[Group E]
- Candidates for mFOLFIRINOX based on accepted standard of care
Exclusion Criteria
- Brain metastases unless previously treated and well controlled for at least 3 months
prior to study day 1
- 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 (or 5 half-lives for systemic agents, whichever is shorter) from
prior anticancer therapy including chemotherapy, hormonal, investigational, and/or
biological therapies and irradiation (except for ongoing hormonal therapy for prostate
cancer)
- Major surgery within 28 days of Study Day 1
- History of anaphylactic reaction to human, or humanized, antibody
- Pregnant or currently breast-feeding
- Known HIV, Hepatitis B or C-positive
- Psychiatric illness/social situations that would interfere with compliance with study
requirements
- Significant cardiovascular risk (e.g., coronary stenting within 4 weeks, 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: | Determine the safety (treatment related adverse events as assessed by Common Toxicity Criteria for Adverse Events [CTCAE] V5.0) of MVT-5873 on a Q2 week schedule |
| Time Frame: | Through study completion. Estimated at one year |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Evaluate the safety profile (treatment related adverse events as assessed by CTCAE V5.0) of MVT-5873 in subjects without circulating CA19-9 expression |
| Time Frame: | Through study completion. Estimated at one year |
| Safety Issue: | |
| Description: | |
| Measure: | Evaluate pharmacokinetics (PK): Area Under the Curve (AUC) for MVT-5873 |
| Time Frame: | Through study completion. Estimated at one year |
| Safety Issue: | |
| Description: | Determined using non-compartmental model. |
| Measure: | Evaluate PK: Maximum concentration (Cmax) for MVT-5873 |
| Time Frame: | Through study completion. Estimated at one year |
| Safety Issue: | |
| Description: | Determined using non-compartmental model. |
| Measure: | Evaluate PK: Plasma half-life (T1/2) for MVT-5873 |
| Time Frame: | Through study completion. Estimated at one year |
| Safety Issue: | |
| Description: | Determined using non-compartmental model. |
| Measure: | Evaluate tumor response rate |
| Time Frame: | Through study completion. Estimated at one year |
| Safety Issue: | |
| Description: | |
| Measure: | Evaluate duration of response |
| Time Frame: | Through study completion. Estimated at one year |
| Safety Issue: | |
| Description: | |
| Measure: | Evaluate time to response |
| Time Frame: | Through study completion. Estimated at one year |
| Safety Issue: | |
| Description: | |
| Measure: | Evaluate progression free survival |
| Time Frame: | Through study completion. Estimated at one year |
| Safety Issue: | |
| Description: | |
| Measure: | Evaluate overall survival |
| Time Frame: | Through study completion. Estimated at one year |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | BioNTech Research & Development, Inc. |
Trial Keywords
- CA19-9 Positive Malignancies
- Pancreatic Cancer and other CA19-9 expressing malignancies
- Pancreatic Ductal Adenocarcinoma (PDAC)
- Sialyl Lewis A (sLea)
Last Updated
April 23, 2021
