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

NCT ID: NCT02672917

Last Updated: 2025-01-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2025-01-14

Brief Summary

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 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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A

MVT-5873 monotherapy dose escalation, initial to MTD

Group Type: EXPERIMENTAL

MVT-5873

Intervention Type: DRUG

intravenous infusion (IV)

Group B

MVT-5873 is administered in Group B every 1 week in combination with gemcitabine and nab-paclitaxel

Group Type: EXPERIMENTAL

MVT-5873

Intervention Type: DRUG

intravenous infusion (IV)

gemcitabine + nab-paclitaxel

Intervention Type: DRUG

IV

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.

Group Type: EXPERIMENTAL

MVT-5873

Intervention Type: DRUG

intravenous infusion (IV)

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.

Group Type: EXPERIMENTAL

MVT-5873

Intervention Type: DRUG

intravenous infusion (IV)

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.

Group Type: EXPERIMENTAL

MVT-5873

Intervention Type: DRUG

intravenous infusion (IV)

modified FOLFIRINOX (mFOLFIRINOX)

Intervention Type: DRUG

IV

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.

Group Type: EXPERIMENTAL

MVT-5873

Intervention Type: DRUG

intravenous infusion (IV)

modified FOLFIRINOX (mFOLFIRINOX)

Intervention Type: DRUG

IV

Interventions

MVT-5873

intravenous infusion (IV)

Intervention Type: DRUG

modified FOLFIRINOX (mFOLFIRINOX)

IV

Intervention Type: DRUG

gemcitabine + nab-paclitaxel

IV

Intervention Type: DRUG

Other Intervention Names

HuMab-5B1

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 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioNTech Research & Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

BioNTech Responsible Person

Role: STUDY_DIRECTOR

BioNTech SE

Locations

HonorHealth Research Institute

Scottsdale, Arizona, United States

The Angeles Clinic & Research Institute

Los Angeles, California, United States

Florida Cancer Specialist and Research Institute

Sarasota, Florida, United States

MSKCC

New York, New York, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

MV-0715-CP-001.01

Identifier Type: -

Identifier Source: org_study_id