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

Pancreatic Cancer Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT02672917
• Other study ID #: MV-0715-CP-001.01
• Status: Recruiting
• Phase: Phase 1
• Start date: January 2016
• Est. completion date: October 2026

Study information

• Verified date: June 2024
• Source: BioNTech SE
• Contact: BioNTech clinical trials patient information
• Phone: +49 6131 9084
• Email: patients[@]biontech.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 264
• Est. completion date: October 2026
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• MVT-5873
intravenous infusion (IV)
• modified FOLFIRINOX (mFOLFIRINOX)
IV
• gemcitabine + nab-paclitaxel
IV

Locations

Country	Name	City	State
United States	The Angeles Clinic & Research Institute	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	MSKCC	New York	New York
United States	Florida Cancer Specialist and Research Institute	Sarasota	Florida
United States	HonorHealth Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
BioNTech Research & Development, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Group D - Determine the MTD and/or RP2D of MVT-5873 on a Q2 week schedule		Through study completion. Estimated at one year
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	All groups - Evaluate PK: Maximum concentration (Cmax) for MVT-5873	Determined using non-compartmental model.	Through study completion. Estimated at one year
Secondary	All groups - Evaluate PK: Plasma half-life (T1/2) for MVT-5873	Determined using non-compartmental model.	Through study completion. Estimated at one year
Secondary	Groups A, B, C, D, E - Evaluate tumor response rate		Through study completion. Estimated at one year
Secondary	Groups A, B, C, D, E - Evaluate duration of response		Through study completion. Estimated at one year
Secondary	Groups A, B, C, D, E - Evaluate time to response		Through study completion. Estimated at one year
Secondary	Groups A, B, C, D, E - Evaluate progression free survival		Through study completion. Estimated at one year
Secondary	All groups - Evaluate overall survival		Through study completion. Estimated at one year
Secondary	Group F - Evaluate disease free survival		Through study completion. Estimated at one year
Secondary	Group F - Evaluate time to recurrence		Through study completion. Estimated at one year