Dose Escalation Study MORAb-066 Targeting Tissue Factor (TF)-Expressing Malignancies Including Breast, Pancreatic, Colorectal, NSCLC

Study Overview

This study is a Phase I, first in human, dose-escalation study of MORAb-066, an investigational humanized immunoglobulin G (IgG) monoclonal antibody (mAb) that targets TF-expressing malignancies that include breast, pancreatic, colorectal, and non-small-cell lung cancer (NSCLC) (adenocarcinoma). This open-label study will assess the safety, tolerability, and pharmacokinetics of MORAb-066 administered weekly. This study will identify the maximum tolerated dose (MTD) when MORAb-066 is administered IV once weekly on a 28-day cycle.

N/A

Breast Cancer
Pancreatic Cancer
Colorectal Cancer
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma

DRUG: MORAb-066

MORAb-066-001

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2013-01-03	Results First Submitted 2022-10-25	Last Update Submitted that met QC Criteria 2023-09-26
First Submitted that Met QC Criteria 2013-01-03	Results First Submitted that Met QC Criteria 2023-09-26	Last Update Posted (ACTUAL) 2024-03-29
First Posted (ACTUAL) 2013-01-04	Results First Posted 2024-03-29	Last Verified 2017-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: MORAb-066 0.1 mg/kg Participants will receive MORAb-066 0.1 milligram per kilogram (mg/kg), infusion intravenously, on Days 1, 8, 15, and 22, in each 28-day treatment cycle until disease progression, participant's discontinuation due to unacceptable toxicity, withdrawal	DRUG: MORAb-066 MORAb-066 infusion.
EXPERIMENTAL: MORAb-066 0.3 mg/kg Participants will receive MORAb-066 0.3 mg/kg, infusion intravenously, on Days 1, 8, 15, and 22, in each 28-day treatment cycle until disease progression, the participant discontinuation due to unacceptable toxicity, withdrawal by participants, or discont	DRUG: MORAb-066 MORAb-066 infusion.
EXPERIMENTAL: MORAb-066 1 mg/kg Participants will receive MORAb-066 1 mg/kg, infusion intravenously, on Days 1, 8, 15, and 22, in each 28-day treatment cycle until disease progression, the participant's discontinuation due to unacceptable toxicity, withdrawal by participants, or di	DRUG: MORAb-066 MORAb-066 infusion.
EXPERIMENTAL: MORAb-066 2 mg/kg Participants will receive MORAb-066 2 mg/kg, infusion intravenously, on Days 1, 8, 15, and 22, in each 28-day treatment cycle until disease progression, the participant's discontinuation due to unacceptable toxicity, withdrawal by participants, or di	DRUG: MORAb-066 MORAb-066 infusion.
EXPERIMENTAL: MORAb-066 3 mg/kg Participants will receive MORAb-066 3 mg/kg, infusion intravenously, on Days 1, 8, 15, and 22, in each 28-day treatment cycle until disease progression, the participant discontinuation due to unacceptable toxicity, withdrawal by participants, or discontin	DRUG: MORAb-066 MORAb-066 infusion.

Primary Outcome Measures	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, blood chemistry, urine values, and vital signs; periodic measurement of electrocardiograms (ECGs) and Eastern Cooperative Oncology Group (ECOG) assessments; and performance of physical examinations.	First dose of study drug (Baseline) up to 30 days after last dose of study drug (Up to approximately 2 years 7 months)

Secondary Outcome Measures	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicity (DLT)	DLT was defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 as any grade 3 or 4 hematemesis, hemoptysis, hematochezia, bright red blood per rectum, epistaxis, gingival bleeding, hemarthrosis, haematuria, uncontrollable menses, or any other bleeding thought to be significant as per assessment of the investigator, regardless of grade.	Cycle 1 (Cycle length=28 days)
Maximum Tolerated Dose (MTD)	The MTD was defined as the highest dose level at which no more than one out of six participants experienced DLT. DLT was defined using NCI CTCAE Version 4.03 as any grade 3 or 4 hematemesis, hemoptysis, hematochezia, bright red blood per rectum, epistaxis, gingival bleeding, hemarthrosis, haematuria, uncontrollable menses, or any other bleeding thought to be significant as per assessment of the investigator, regardless of grade.	Cycle 1 (Cycle length=28 days)
Cmax: Maximum Observed Serum Concentration for MORAb-066		Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
Tmax: Time to Reach Maximum Serum Concentration for MORAb-066		Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
t1/2: Terminal Elimination Phase Half-Life for MORAb-066		Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
AUC(0-t): Area Under the Serum Concentration-time Curve From Zero Time to the Last Measurable Point for MORAb-066		Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
AUC(0-Inf): Area Under the Serum Concentration-time Curve From Zero to Infinity for MORAb-066		Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
Vd: Volume of Distribution for MORAb-066		Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
CL: Total Body Clearance for MORAb-066		Cycle 1 Days 1 and 22: 0-168 hours post-dose (Cycle length=28 days)
Number of Participants With Best Overall Response (BOR)	BOR based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for target and non-target lesions is complete response (CR) or partial response (PR). CR: disappearance of target and non-target lesions, normalization of tumor marker level, all lymph nodes must be non-pathological in size (less than 10 millimeter [mm] short axis). PR: at least 30 percent (%) decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.	Up to approximately 2 years 7 months
Number of Participants Positive for Antidrug Antibodies (ADA)		Up to approximately 2 years 7 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L
Platelets greater than or equal to 100 x 10^9/L
Hemoglobin greater than or equal to 9 g/dL
Prothrombin time/partial thromboplastin time (PT/PTT) within institutional limits of normal
Serum total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3.0 x ULN if no liver involvement or less than or equal to 5 x ULN with liver involvement.
Serum creatinine less than or equal to 1.5 x ULN or calculated creatinine clearance greater than or equal to 50 mL/min as calculated by the Cockcroft-Gault method, OR 24-hour measured urine creatinine clearance greater than or equal to 50 mL/min. 6. Life expectancy of greater than or equal to 12 weeks. 7. Female patients of child-bearing potential (see Appendix C), and all male patients must consent to use a medically acceptable method of contraception throughout the study period and for 30 days after their last MORAb-066 administration. A barrier method of contraception must be included. 8. Patients must be greater than or equal to 18 years of age. 9. Patients entering this study will be asked to provide archival tissue from a previous tumor biopsy (if available) for correlative testing. If tissue is not available, the subject will still be eligible for enrollment into the study. 10. Ability to understand the nature of this study and give written informed consent.

Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction function
QTcF greater than 470 msec
History of documented congestive heart failure (New York Heart Association functional classification III-IV [see Appendix B])
Angina not well-controlled by medication 15. A serious active infection (bacterial or fungal) at the time of treatment, or another serious underlying medical condition that would impair the ability of the subject to receive protocol treatment. 16. Chronic inflammatory disorder(e.g., inflammatory bowel disease, active vasculitis). 17. Herbal preparations/medications must be discontinued 7 days prior to first dose of study drug (see Section 5.3.1). 18. Known diagnosis of human immunodeficiency virus, Hepatitis B or Hepatitis C. 19. History or current diagnosis of glomerulonephritis 20. History of clinically significant or current diagnosis of hematuria. 21. Women who are pregnant or lactating. 22. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. 23. Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol. 24. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

SCRI Development Innovations, LLC

Investigators

Publications

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