Study Of HuMab-5B1 (MVT-5873) In Subjects With Pancreatic Cancer Or Other Cancer Antigen 19-9 (CA19-9) Positive Malignancies

Study Overview

Study of HuMab-5B1 (MVT-5873) in Subjects With Pancreatic Cancer or Other Cancer Antigen 19-9 (CA19-9) Positive Malignancies

Phase 1 Safety and Tolerability Study in Subjects with Pancreatic Cancer or Other CA19-9 Positive Malignancies.

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 was designed to 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 utilized a conventional 3+3 study design to identify the MTD and recommended phase 2 dose (RP2D). Following the definition of the MTD in each group, the RP2D of MVT-5873 as a single agent and in combination with mFOLFIRINOX was defined. Following completion of monotherapy dose escalation, an expansion cohort of 30 additional subjects was treated at the RP2D for Group D. Subjects were subdivided into two groups of 15 subjects; those without peripheral blood expression of C19-9 and those with peripheral blood expression of CA19-9. MVT-5873 pharmacokinetics (PK) and pharmacodynamics (PD) were determined for each group.

Pancreatic Cancer

DRUG: MVT-5873
DRUG: modified FOLFIRINOX (mFOLFIRINOX)
DRUG: gemcitabine + nab-paclitaxel

MV-0715-CP-001.01

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2016-01-25	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-01-24
First Submitted that Met QC Criteria 2016-01-30	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-01-28
First Posted (ACTUAL) 2016-02-03	Results First Posted N/A	Last Verified 2025-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Group A MVT-5873 monotherapy dose escalation, initial to MTD	DRUG: MVT-5873 intravenous infusion (IV)
EXPERIMENTAL: Group B MVT-5873 is administered in Group B every 1 week in combination with gemcitabine and nab-paclitaxel	DRUG: MVT-5873 intravenous infusion (IV) DRUG: gemcitabine + nab-paclitaxel IV
EXPERIMENTAL: Group C MVT-5873 is administered in Group C every 4 weeks by intravenous infusion following a lead in dose. 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.	DRUG: MVT-5873 intravenous infusion (IV)
EXPERIMENTAL: Group D MVT-5873 is administered in Group D every 2 weeks by intravenous infusion following a lead in dose. During dose escalation, doses of MVT-5873 will be increased to defined the MTD. Up to 30 patients will be treated at the RP2D.	DRUG: MVT-5873 intravenous infusion (IV)
EXPERIMENTAL: Group E - metastatic 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 mFOLFIRI	DRUG: MVT-5873 intravenous infusion (IV) DRUG: modified FOLFIRINOX (mFOLFIRINOX) IV
EXPERIMENTAL: Group F - adjuvant 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 mFOLFIRI	DRUG: MVT-5873 intravenous infusion (IV) DRUG: modified FOLFIRINOX (mFOLFIRINOX) IV

Primary Outcome Measures	Measure Description	Time Frame
Group D - 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		Through study completion. Estimated at one year
Group D - Determine the MTD and/or RP2D of MVT-5873 on a Q2 week schedule		Through study completion. Estimated at one year
Group E - Determine the safety (treatment related adverse events as assessed by CTCAE V5.0) of MVT-5873 in combination with the modified FOLFIRINOX regimen (mFOLFIRINOX) in the metastatic disease setting		Through study completion. Estimated at one year
Group E - Determine the MTD and/or the RP2D of MVT-5873 in combination with the modified FOLFIRINOX regimen (mFOLFIRINOX) in the metastatic disease setting		Through study completion. Estimated at one year
Group F - Determine the safety (treatment related adverse events as assessed by CTCAE V5.0) of MVT-5873 in combination with the modified FOLFIRINOX regimen (mFOLFIRINOX) in the PDAC adjuvant setting		Through study completion. Estimated at one year
Group F - Determine the MTD and/or the RP2D of MVT-5873 administered in combination with the modified FOLFIRINOX regimen (mFOLFIRINOX) in the PDAC adjuvant setting		Through study completion. Estimated at one year

Secondary Outcome Measures	Measure Description	Time Frame
Group D - Evaluate the hepatic safety profile (treatment related adverse events as assessed by CTCAE V5.0) of MVT-5873 in participants without elevated circulating CA19-9 expression		Through study completion. Estimated at one year
All groups - Evaluate pharmacokinetics (PK): Area Under the Curve (AUC) for MVT-5873	Determined using non-compartmental model.	Through study completion. Estimated at one year
All groups - Evaluate PK: Maximum concentration (Cmax) for MVT-5873	Determined using non-compartmental model.	Through study completion. Estimated at one year
All groups - Evaluate PK: Plasma half-life (T1/2) for MVT-5873	Determined using non-compartmental model.	Through study completion. Estimated at one year
Groups A, B, C, D, E - Evaluate tumor response rate		Through study completion. Estimated at one year
Groups A, B, C, D, E - Evaluate duration of response		Through study completion. Estimated at one year
Groups A, B, C, D, E - Evaluate time to response		Through study completion. Estimated at one year
Groups A, B, C, D, E - Evaluate progression free survival		Through study completion. Estimated at one year
All groups - Evaluate overall survival		Through study completion. Estimated at one year
Group F - Evaluate disease free survival		Through study completion. Estimated at one year
Group F - Evaluate time to recurrence		Through study completion. Estimated at one year

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

Evaluable or measurable disease based on RECISTv1.1

Progression following treatment with standard of care for the subject's specific tumor type

Measurable disease based on RECISTv1.1

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)

Candidates for mFOLFIRINOX based on accepted standard of care

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

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)

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: BioNTech Responsible Person, BioNTech SE

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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