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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: MVT-5873
* Drug: modified FOLFIRINOX (mFOLFIRINOX)
* Drug: gemcitabine + nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>MVT-5873 monotherapy dose escalation, initial to maximum tolerated dose | Drug: MVT-5873<br>* intravenous infusion (IV)<br>* Other names: HuMab-5B1;|
| Experimental: Group B<br>MVT-5873 is administered in Group B every 1 week in combination with gemcitabine and nab-paclitaxel | Drug: MVT-5873<br>* intravenous infusion (IV)<br>* Other names: HuMab-5B1;Drug: gemcitabine + nab-paclitaxel<br>* IV<br>|
| Experimental: Group C<br>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<br>* intravenous infusion (IV)<br>* Other names: HuMab-5B1;|
| Experimental: Group D<br>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<br>* intravenous infusion (IV)<br>* Other names: HuMab-5B1;|
| Experimental: Group E - metastatic<br>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<br>* intravenous infusion (IV)<br>* Other names: HuMab-5B1;Drug: modified FOLFIRINOX (mFOLFIRINOX)<br>* IV<br>|
| Experimental: Group F - adjuvant<br>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<br>* intravenous infusion (IV)<br>* Other names: HuMab-5B1;Drug: modified FOLFIRINOX (mFOLFIRINOX)<br>* IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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

| Outcome Measure | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CA19-9 Positive Malignancies, Pancreatic Cancer and other CA19-9 expressing malignancies, Pancreatic Ductal Adenocarcinoma (PDAC), Sialyl Lewis A (sLea)