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Pre-operative escalation doses of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment

Pre-operative RD of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment

1 mg/kg or 3 mg/kg for pre-operative dose, 1 mg/kg during post-operative period

MVT-5873

pancreatectomy or hepatectomy

Jonathan M Hernandez, M.D.

Background:

Gastrointestinal tumors have a molecule called carbohydrate antigen 19-9 (CA19-9) in the tumors and blood. The agent MVT-5873 was designed to block this molecule. Researchers want to test how safe it is to give this agent to people before and after surgery to remove a tumor. They want to learn the highest dose tolerated. They want to see if getting the agent at surgery helps slow down the disease.

Objective:

To test the safety of giving MVT-5873 at surgery to remove cancer and see if it slows the progression of the disease.

Eligibility:

Adults at least 18 years old with certain cancers and certain blood CA19-9 levels

Design:

Participants will be screened with:

* Medical history
* Physical exam
* Blood and heart tests
* Scans
* Review of normal activities
* Review of tumor sample
* Pregnancy test

A few days before surgery, participants will get a dose of the study agent. They will get it through a small plastic tube in a vein over about 2 hours.

Participants will sign a separate consent and have the surgery. A sample of the tumor and normal liver will be removed for research.

For 1-2 weeks after surgery, participants will recover in intensive care then regular care at the hospital. They will be monitored and treated throughout the stay.

After leaving the hospital, participants will get the study agent every week for 1 month. Then they will get it every other week for 2 months. They will repeat screening tests at study visits and at a follow-up visit. That will be about 5 weeks after the last dose.

Background:

* Resections to remove tumors in the liver, bile ducts and pancreas are rarely curative, and patients frequently succumb to disease recurrence in the ensuing months to year(s) after the operation.
* Standard adjuvant therapies, which typically begin 6-12 weeks after surgery, offer little demonstrable decreases in the rates of tumor recurrence.
* The concept and implementation of immediate perioperative therapy has not been evaluated given the serious concerns related to healing and recovery with standard cytotoxic chemotherapy and newer targeted agents.
* A significant percentage of metastatic colorectal cancers, and primary tumors of the pancreas and bile ducts express Sialyl Lewis, an epitope on the well-established tumor marker, Carbohydrate antigen 19-9 (CA19-9).
* MVT-5873, a fully human antibody against Sialyl Lewis, has displayed antibody-dependent cell-mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) in vitro, potentiated chemotherapeutic efficacy in mouse models and demonstrated efficacy in Phase 1 trials of patients with advanced inoperable Hepato-pancreato-biliary (HPB) cancers.
* MVT-5873 is well tolerated as a single agent; moderate elevations in aspartate aminotransferase (AST)/alanine aminotransferase (ALT) appear to be dose-limiting.
* Patients with resectable Sialyl Lewis-expressing cancers represent an ideal population to explore the use of perioperative MVT-5873 given moderate level of CA 19-9 elevations, and the potential for extension of recurrence-free survival.

Objectives:

* Document the safety of perioperative MVT-5873 in patients undergoing pancreas and liver resections.
* Determine if perioperative MVT-5873 can decrease 1-year recurrence rates for patients with operable CA 19-9-producing cancers.

Eligibility:

* Histologically or cytologically confirmed adenocarcinoma of the

  * Colon (metastatic to liver)
  * Pancreas
  * Bile Ducts (Cholangiocarcinoma)
* Serum CA19-9 levels greater than the upper limit of normal, but less than 2500.
* Disease amenable to complete surgical extirpation.

Design:

-Pre-operative one-time treatment with MVT-5873, resection to remove all demonstrable disease in the liver, bile ducts and pancreas, and continuing MVT-5873 mono-therapy until off treatment criteria are met.

Perioperative MVT-5873, a Fully Human Monoclonal Antibody Against a CA 19-9 Epitope, for Operable CA 19-9 Producing Pancreatic Cancers, Cholangiocarcinomas, and Metastatic Colorectal Cancers

All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to database of Genotypes and Phenotypes (dbGaP).

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Disease recurrence is defined as new disease measurable on computed tomography (CT)/magnetic resonance imaging (MRI) that was not present on the baseline CT/MRI.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse events.

Disease free survival is defined as resection day of surgery Day 0 (D0) until the time of documented clinical recurrence (radiographically or pathologically). In the absence of a knowable time of recurrence, time of death will be used as a surrogate. Clinical recurrence is cancer that has recurred during which the cancer could not be detected. This is judged on computed tomography (CT) or magnetic resonance imaging (MRI) as compared to the scan obtained after surgery and completion of the study drug.

National Cancer Institute (NCI)

Investigator

Pre-operative escalation doses of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment

MVT-5873: 1 mg/kg for pre-operative dose, 1 mg/kg during post-operative period

pancreatectomy or hepatectomy: Pancreatectomy or hepatectomy

Participants having low elevated liver function tests (LFTs), enrolled into pre-operative MVT-5873 escalation dose levels.

Cohort 1 - Pre-operative Escalation Doses of MVT-5873 (HuMab-5B1)

Pre-operative RD of MVT-5873, pancreatectomy or hepatectomy and post-operative MVT-5873 treatment

MVT-5873: 1 mg/kg for pre-operative dose, 1 mg/kg during post-operative period

pancreatectomy or hepatectomy: Pancreatectomy or hepatectomy

Participants having moderate elevated liver function tests (LFTs), enrolled into pre-operative MVT-5873 escalation dose levels.

Cohort 2 - Pre-operative Recommended Dose (RD) of MVT-5873 (HuMab-5B1)

Enrolled But Not Treated

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

One participant was enrolled but not treated. However, collected baseline data is reported here.

Dr. Jonathan Hernandez

Number of Participants With Disease Recurrence At 1 Year

Grade 3 Abdominal pain - Not Related

Grade 3 Abdominal infection - Not Related

Grade 3 Alanine aminotransferase increased - Not Related

Grade 3 Alkaline phosphatase increased - Not Related

Grade 3 Anemia - Not Related

Grade 3 Aspartate aminotransferase increased - Not Related

Grade 3 Back pain - Not Related

Grade 3 Blood bilirubin increased - Not Related

Grade 3 Confusion - Not Related

Grade 3 Dyspnea - Not Related

Grade 3 Hematuria - Not Related

Grade 3 Hepatobiliary disorders- Other, Bile duct perforation - Not Related

Grade 3 Hyperglycemia - Not Related

Grade 3 Hypermagnesemia - Not Related

Grade 3 Hypertension - Not Related

Grade 3 Hypoalbuminemia - Not Related

Grade 3 Hypokalemia - Not Related

Grade 3 Hyponatremia - Not Related

Grade 3 Hypotension - Not Related

Grade 3 Lymphocyte count decreased - Not Related

Grade 3 Pharyngitis - Not Related

Grade 3 Thromboembolic event - Not Related

Grade 3 Urine output decreased - Not Related

Grade 3 Vomiting - Not Related

Grade 3 Alkaline phosphatase increased - Related

Grade 3 Anemia - Related

Grade 3 Aspartate aminotransferase increased - Related

Grade 3 Alanine aminotransferase increased - Related

Grade 3 Blood bilirubin increased - Related

Grade 3 Lymphocyte count decreased - Related

Grade 4 Aspartate aminotransferase increased - Not Related

Grade 4 Lymphocyte count increased - Not Related

Grade 4 Alkaline phosphatase increased - Related

Grade 5 Adverse Event - Not Related

Grade 5 Adverse Event - Related

Number of Grade 3-5 Adverse Events Related and/or Not Related to Drug

5/8 participants were analyzed in cohort 1 because 2 participants were found to have peritoneal metastases on Day 0 and were taken off study, and 1 participant was taken off study due to study closure.

Define Disease Free Survival (DFS) for Participants Treated With Preoperative MVT-5873

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Overall Study

Spots Global Cancer Trial Database for well tolerated agent