Sponsor decision

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

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.

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