Study of HuMab-5B1 (MVT-5873) in Subjects With Pancreatic Cancer or Other Cancer Antigen 19-9 (CA19-9) Positive Malignancies
- Conditions
- Pancreatic Cancer
- Interventions
- Registration Number
- NCT02672917
- Lead Sponsor
- BioNTech Research & Development, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 264
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Group C MVT-5873 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 E - metastatic modified FOLFIRINOX (mFOLFIRINOX) 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 B gemcitabine + nab-paclitaxel MVT-5873 is administered in Group B every 1 week in combination with gemcitabine and nab-paclitaxel Group D MVT-5873 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 F - adjuvant modified FOLFIRINOX (mFOLFIRINOX) 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 E - metastatic MVT-5873 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 A MVT-5873 MVT-5873 monotherapy dose escalation, initial to MTD Group B MVT-5873 MVT-5873 is administered in Group B every 1 week in combination with gemcitabine and nab-paclitaxel Group F - adjuvant MVT-5873 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.
- Primary Outcome Measures
Name Time Method 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 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 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
- Secondary Outcome Measures
Name Time Method Group F - Evaluate disease free survival Through study completion. Estimated at one year Groups A, B, C, D, E - Evaluate time to response Through study completion. Estimated at one year All groups - Evaluate overall survival Through study completion. Estimated at one year 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 Through study completion. Estimated at one year Determined using non-compartmental model.
Groups A, B, C, D, E - Evaluate tumor response rate Through study completion. Estimated at one year All groups - Evaluate PK: Maximum concentration (Cmax) for MVT-5873 Through study completion. Estimated at one year Determined using non-compartmental model.
All groups - Evaluate PK: Plasma half-life (T1/2) for MVT-5873 Through study completion. Estimated at one year Determined using non-compartmental model.
Groups A, B, C, D, E - Evaluate progression free survival Through study completion. Estimated at one year Group F - Evaluate time to recurrence Through study completion. Estimated at one year Groups A, B, C, D, E - Evaluate duration of response Through study completion. Estimated at one year
Trial Locations
- Locations (5)
The Angeles Clinic & Research Institute
🇺🇸Los Angeles, California, United States
Florida Cancer Specialist and Research Institute
🇺🇸Sarasota, Florida, United States
HonorHealth Research Institute
🇺🇸Scottsdale, Arizona, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
MSKCC
🇺🇸New York, New York, United States