Phase 1 Study of Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody in Solid Tumors

NCT01765790 | Completed Phase 1

• 2 other identifiers: 3911012013-002870-31
• Study Type: interventional
• Target: 68
• Locations: 2 countries
• Sites: 5

Brief Summary

The purpose of the study is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of anti-MIF antibody in subjects with malignant solid tumors (Arm 1) and in subjects with metastatic adenocarcinoma of the colon or rectum (Arm 2).

Conditions

Metastatic Adenocarcinoma of the Colon or Rectum; Malignant Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Number of participants experiencing serious adverse events (SAEs) and/or adverse events (AEs) regardless of causality

  14 months

Secondary Outcomes (12)

• Plasma pharmacokinetic parameters

  28 days

• Tumor response

  14 months

• Levels of free active MIF and free total MIF in plasma and tumor tissue (where applicable)

  14 months

• Change in levels of tumor-associated biomarkers, if applicable based on cancer type, following treatment with anti-MIF antibody

  14 months

• Number of serious adverse events (SAEs) and/or adverse events (AEs), regardless of causality

  14 Months

Study Arms (2)

Malignant Solid Tumor (Arm 1)

EXPERIMENTAL

Dose Escalation Phase- Standard dose escalation of anti-MIF antibody in 5 dose groups of 3-6 participants each according to 3+3 design: 1. Dose escalation will be performed after safety data review, following completion of dosing of each cohort. -\> 2. Safety data review. If dose escalation permissible -\> 3. Next dose group -\> 4. Safety data review, etc. Dose Expansion Phase- Enrollment of up to 6 participants to receive anti-MIF antibody (at the maximum tolerated dose or lower) in order to gain further experience with the investigational product at a specific dose level(s).

Biological: Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody

Metastatic Adenocarcinoma of the Colon or Rectum (Arm 2)

EXPERIMENTAL

Dose Escalation Phase- Standard dose escalation of anti-MIF antibody in 3 dose groups of 3-6 participants each according to 3+3 design: 1. Dose escalation will be performed after safety data review, following completion of dosing of each cohort. -\> 2. Safety data review. If dose escalation permissible -\> 3. Next dose group -\> 4. Safety data review, etc. Dose Expansion Phase- Enrollment of up to 6 participants to receive anti-MIF antibody (at the maximum tolerated dose or lower) in order to gain further experience with the investigational product at a specific dose level(s).

Biological: Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody

Interventions

Anti-Macrophage Migration Inhibitory Factor (Anti-MIF) Antibody BIOLOGICAL

* Dosing every 2 weeks * Intravenous injection

Malignant Solid Tumor (Arm 1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females 18 years of age and older at the time of screening
• Anticipated life expectancy \> 3 months at the time of screening
• Arm 1 only: Histologically confirmed malignant solid tumor which is refractory to or has failed standard treatments, or participant is not considered medically suitable to receive standard of care treatment or refuses standard of care treatment
• Arm 2 only: Histologically or cytologically confirmed diagnosis of metastatic adenocarcinoma of the colon or rectum which is refractory to or has failed standard treatments, or participant is not considered medically suitable to receive standard of care treatment or refuses standard of care treatment
• Measurable or evaluable disease (as defined in the study protocol)
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Adequate hematological function (as defined in the study protocol)
• Adequate renal function (as defined in the study protocol)
• Adequate liver function (as defined in the study protocol)
• Adequate venous access
• Arm 2 only: At least 1 tumor that is amenable to biopsy, as determined by the investigator, and participant must be willing to undergo a biopsy prior to and at least once following anti-macrophage migration inhibitory factor (anti-MIF) antibody treatment
• For women of childbearing potential, the participant must have a negative pregnancy test at screening and must agree to employ 2 forms of adequate contraceptive measures
• For males, participants must agree to use adequate contraceptive measures including at least 1 barrier method, and abstain from sperm donation throughout the course of the study and for at least 90 days after the last administration of investigational product.
• Participant is willing and able to comply with the requirements of the protocol

You may not qualify if:

• Known brain tumors or Central nervous system (CNS) metastases
• Myocardial infarction within 6 months of anti-MIF antibody administration, congestive heart failure (New York Heart Association Class III or Class IV), unstable angina, unstable cardiac arrhythmia requiring medication, or risk factors for polymorphic ventricular tachycardia
• Uncontrolled hypertension
• Left ventricular ejection fraction (LVEF) \<40%, as determined by screening echocardiogram (echocardiogram results obtained within 90 days prior to screening are acceptable)
• QT/QTc interval \>450 msec, as determined by screening electrocardiogram (ECG)
• Antitumor therapy (chemotherapy, radiotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, or hormonal therapy) within 4 weeks prior to administration of the investigational product (IP) (6 weeks for nitrosoureas and mitomycin C). Any previous treatment-related toxicities must have recovered to Grade ≤ 1 (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03). Prior and concurrent use of hormone deprivation therapies for hormone-refractory prostate cancer or breast cancer are permitted.
• Major surgery within 4 weeks prior to IP administration
• Active joint inflammation or history of inflammatory arthritis or other immune disorder involving the joints
• Active infection requiring IV antibiotics within 2 weeks prior to screening
• Known history of hepatitis B virus (HBV), hepatitis C virus (HCV), or active tuberculosis. Known history of human immunodeficiency virus (HIV) type 1/2 or other immunodeficiency disease.
• Participant has received a live vaccine within 4 weeks prior to screening
• Known hypersensitivity to any component of recombinant protein production by Chinese Hamster Ovary (CHO) cells
• Participant has been exposed to an investigational product (IP) or investigational device in another clinical study within 4 weeks prior to IP administration, or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study
• Participant is nursing or intends to begin nursing during the course of the study
• Any disorder or disease, or clinically significant abnormality on laboratory or other clinical test(s), that in medical judgment may impede the participant's participation in the study, pose increased risk to the participant, or confound the results of the study

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (5)

Scottsdale Healthcare

Scottsdale, Arizona, 85258, United States

Location

Florida Cancer Specialists / Sarah Cannon Research Institute

Sarasota, Florida, 34232, United States

Location

Department of Investigator Cancer Therapeutics, University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Cancer Therapy and Research Center (CTRC), The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

Heidelberg, 69120, Germany

Location

Related Publications (1)

• Mahalingam D, Patel MR, Sachdev JC, Hart LL, Halama N, Ramanathan RK, Sarantopoulos J, Volkel D, Youssef A, de Jong FA, Tsimberidou AM. Phase I study of imalumab (BAX69), a fully human recombinant antioxidized macrophage migration inhibitory factor antibody in advanced solid tumours. Br J Clin Pharmacol. 2020 Sep;86(9):1836-1848. doi: 10.1111/bcp.14289. Epub 2020 Apr 12.

  PMID: 32207164 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Antibodies

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2013
• First Posted: January 10, 2013
• Study Start: June 14, 2012
• Primary Completion: July 28, 2016
• Study Completion: July 28, 2016
• Last Updated: May 5, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

DE (1); US (4)