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

• ClinicalTrials.gov Identifier: NCT02672917
• Recruitment Status: Recruiting
• First Posted: February 3, 2016
• Last Update Posted: May 9, 2023
• Sponsor: BioNTech Research & Development, Inc.
• Information provided by (Responsible Party): BioNTech SE ( BioNTech Research & Development, Inc. )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer	Drug: MVT-5873; Drug: modified FOLFIRINOX (mFOLFIRINOX); Drug: gemcitabine + nab-paclitaxel	Phase 1

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 264 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 2016
• Estimated Primary Completion Date: February 2024
• Estimated Study Completion Date: February 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A; MVT-5873 monotherapy dose escalation, initial to maximum tolerated dose	Drug: MVT-5873; intravenous infusion (IV); Other Name: HuMab-5B1
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); Other Name: HuMab-5B1; 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); Other Name: HuMab-5B1
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 he MTD. Up to 30 patients will be treated at the RP2D.	Drug: MVT-5873; intravenous infusion (IV); Other Name: HuMab-5B1
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 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.	Drug: MVT-5873; intravenous infusion (IV); Other Name: HuMab-5B1; 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 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.	Drug: MVT-5873; intravenous infusion (IV); Other Name: HuMab-5B1; Drug: modified FOLFIRINOX (mFOLFIRINOX); IV

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Through study completion. Estimated at one year ]
2. Group D - Determine the MTD and/or RP2D of MVT-5873 on a Q2 week schedule [ Time Frame: Through study completion. Estimated at one year ]
3. 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 [ Time Frame: Through study completion. Estimated at one year ]
4. 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 [ Time Frame: Through study completion. Estimated at one year ]
5. 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 [ Time Frame: Through study completion. Estimated at one year ]
6. 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 [ Time Frame: Through study completion. Estimated at one year ]

Secondary Outcome Measures :

1. 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 [ Time Frame: Through study completion. Estimated at one year ]
2. All groups - Evaluate pharmacokinetics (PK): Area Under the Curve (AUC) for MVT-5873 [ Time Frame: Through study completion. Estimated at one year ]
   Determined using non-compartmental model.
3. All groups - Evaluate PK: Maximum concentration (Cmax) for MVT-5873 [ Time Frame: Through study completion. Estimated at one year ]
   Determined using non-compartmental model.
4. All groups - Evaluate PK: Plasma half-life (T1/2) for MVT-5873 [ Time Frame: Through study completion. Estimated at one year ]
   Determined using non-compartmental model.
5. Groups A, B, C, D, E - Evaluate tumor response rate [ Time Frame: Through study completion. Estimated at one year ]
6. Groups A, B, C, D, E - Evaluate duration of response [ Time Frame: Through study completion. Estimated at one year ]
7. Groups A, B, C, D, E - Evaluate time to response [ Time Frame: Through study completion. Estimated at one year ]
8. Groups A, B, C, D, E - Evaluate progression free survival [ Time Frame: Through study completion. Estimated at one year ]
9. All groups - Evaluate overall survival [ Time Frame: Through study completion. Estimated at one year ]
10. Group F - Evaluate disease free survival [ Time Frame: Through study completion. Estimated at one year ]
11. Group F - Evaluate time to recurrence [ Time Frame: Through study completion. Estimated at one year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

[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 Expansion and Group E Escalation and Expansion]

• Measurable disease based on RECISTv1.1

[Group C and D 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]

• 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 C1D1
• Baseline scans without evidence of disease (e.g., CT/MRI)
• 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

Contacts and Locations

Contacts

Contact: BioNTech clinical trials patient information; +49 6131 9084 ext 0; patients@biontech.de

Locations

United States, Arizona

HonorHealth Research Institute; Recruiting

Scottsdale, Arizona, United States, 85258

Contact: Erkut Borazanci, MD

United States, California

The Angeles Clinic & Research Institute; Recruiting

Los Angeles, California, United States, 90025

Contact: Vi Chiu, MD

United States, Florida

Florida Cancer Specialist and Research Institute; Recruiting

Sarasota, Florida, United States, 34233

Contact: Judy Wang, MD

United States, New York

MSKCC; Recruiting

New York, New York, United States, 10065

Contact: Eileen O'Reilly, MD

United States, Tennessee

Sarah Cannon Research Institute; Recruiting

Nashville, Tennessee, United States, 37203

Contact: Meredith Pelster, MD

Sponsors and Collaborators

BioNTech Research & Development, Inc.

Investigators

• Study Director: BioNTech Responsible Person; BioNTech SE

More Information

• Responsible Party: BioNTech Research & Development, Inc.
• ClinicalTrials.gov Identifier: NCT02672917
• Other Study ID Numbers: MV-0715-CP-001.01
• First Posted: February 3, 2016
• Last Update Posted: May 9, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by BioNTech SE ( BioNTech Research & Development, Inc. ):

CA19-9 Positive Malignancies; Pancreatic Cancer and other CA19-9 expressing malignancies; Pancreatic Ductal Adenocarcinoma (PDAC); Sialyl Lewis A (sLea)

Additional relevant MeSH terms:

Pancreatic Neoplasms; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Paclitaxel; Gemcitabine; Folfirinox; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites