Pancreatic Cancer
Conditions
Keywords
CA19-9 Positive Malignancies, Pancreatic Cancer and other CA19-9 expressing malignancies, Pancreatic Ductal Adenocarcinoma (PDAC), Sialyl Lewis A (sLea)
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.
Interventions
DRUGMVT-5873
intravenous infusion (IV)
Sponsors
BioNTech Research & Development, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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 | — |
| All groups - Evaluate overall survival | 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. |
| 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 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 | — |
Countries
United States
Outcome results
None listed