Study of HuMab-5B1 (MVT-5873) in Subjects With Pancreatic Cancer or Other Cancer Antigen 19-9 (CA19-9) Positive Malignancies
Status and phase
Conditions
Treatments
Details and patient eligibility
About
Phase 1 Safety and Tolerability Study in Subjects with Pancreatic Cancer or Other CA19-9 Positive Malignancies.
Full description
Open label, multicenter, non-randomized, dose escalation/expansion trial of MVT-5873 as a single agent and in combination with standard of care chemotherapy or 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 as monotherapy (Group A), in combination with a standard of care chemotherapy (Group B), 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 (Groups E and F). 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 the respective 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.
Group A, B, and C are no longer open for enrollment.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria [all groups]
- 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 and for up to at least 9 months after the last Oxaliplatin dose.
[Group A, C, and Group D Dose Escalation]
- Evaluable or measurable disease based on RECISTv1.1
[Group A, C, and D]
- Progression following treatment with standard of care for the subject's specific tumor type
[Group C and D Dose Expansion and Group E Dose Escalation and Expansion]
- Measurable disease based on RECISTv1.1
[Group C and D Dose Expansion, non-PDAC malignancies]
- If 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 (based on institutional determination of CA19-9)
[Group E and F]
- Candidates for mFOLFIRINOX based on accepted standard of care
[Group F]
- Histologically or cytologically confirmed PDAC
- Macroscopically complete resection (R0 or R1 resection) performed between ≥21 and ≤84 days prior to Cycle 1, Day 1 (C1D1)
- Baseline scans without evidence of disease (e.g., CT/MRI)
- Serum CA19-9 ≤ 180 U/mL within 21 days of C1D1
- Full recovery from surgery and able to receive chemotherapy
- Free of significant nausea and vomiting
- No prior radiotherapy or chemotherapy
Exclusion Criteria [Groups A, B, C, D, and E]
- 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)
[Group F]
- Incomplete macroscopic tumor removal (R2 resection)
- Other known active cancer(s) likely to require treatment in the next 2 years
- Active, uncontrolled bacterial, viral, or fungal infection (s) requiring systemic therapy
- 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)
- Pre-existing neuropathy
- Known homozygous for UGT1A1*28 mutation
- Inflammatory disease of the colon or rectum, or occlusion or sub-occlusion of the intestine or severe postoperative uncontrolled diarrhea
Trial design
Primary purpose
Allocation
Interventional model
Masking
118 participants in 6 patient groups
Trial contacts and locations
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Central trial contact
BioNTech clinical trials patient information
Data sourced from clinicaltrials.gov
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