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

NCT01761240 | Completed Phase 1 Results DMC

• 1 other identifier: MORAb-066-001
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Number of Participants With Dose Limiting Toxicity (DLT)

  Cycle 1 (Cycle length=28 days)

• Maximum Tolerated Dose (MTD)

  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)

Study Arms (5)

MORAb-066 0.1 mg/kg

EXPERIMENTAL

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 by participants, or discontinuation by study physician decision.

Drug: MORAb-066

MORAb-066 0.3 mg/kg

EXPERIMENTAL

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 discontinuation by study physician decision.

Drug: MORAb-066

MORAb-066 1 mg/kg

EXPERIMENTAL

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 discontinuation by study physician decision.

Drug: MORAb-066

MORAb-066 2 mg/kg

EXPERIMENTAL

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 discontinuation by study physician decision.

Drug: MORAb-066

MORAb-066 3 mg/kg

EXPERIMENTAL

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 discontinuation by study physician decision.

Drug: MORAb-066

Interventions

MORAb-066 DRUG

MORAb-066 infusion.

MORAb-066 0.1 mg/kg; MORAb-066 0.3 mg/kg; MORAb-066 1 mg/kg; MORAb-066 2 mg/kg; MORAb-066 3 mg/kg

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the following criteria in order to be included in this clinical trial:
• Histologically or cytologically confirmed diagnosis of breast, colorectal, pancreas, or NSCLC (adenocarcinoma) that is metastatic or unresectable for which there is no effective therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 (see Appendix A).
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Subject has recovered (to Grade less than or equal to 1) from all clinically significant toxicities related to prior antineoplastic therapies with the exception of alopecia and bone marrow and organ functions (described separately below).
• Adequate organ system function less than or equal to 2 weeks prior to Day1, defined as follows:
• 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.
• Life expectancy of greater than or equal to 12 weeks.
• 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.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from trial entry:
• Patients currently receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization).
• Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of MORAb-066. For investigational drugs for which 5 half-lives is less than 21 days, a minimum of 10 days between termination of the investigational drug and administration of MORAb-066 is required.
• Any major surgery, chemotherapy, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed greater than or equal to 2 weeks).
• Subject has received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) less than or equal to 28 days or limited field radiation for palliation less than or equal to 14 days prior to starting study drug or has not recovered from side effects of such therapy.
• Known intracranial involvement, leptomeningeal metastases or spinal cord compression due to disease.
• Known allergy or hypersensitivity to monoclonal antibodies.
• Known bleeding diathesis, such as factor deficiency, factor inhibitor, platelet disorder, or who are on active anticoagulation, or any dose of aspirin within 5 days prior to first dose of MORAb-066.
• Known prior significant bleeding history.
• Patients with ureteral stents or 3+ blood in the urine at baseline.
• Patients who are receiving chronic systemic anticoagulation therapy (warfarin sodium or heparin, etc.).
• Patients who received a previous mAb therapy and have evidence of an immune or allergic reaction or previously documented HAHA reaction.
• A serious non-healing wound, active ulcer, or untreated bone fracture. An abdominal fistula or gastrointestinal perforation less than 6 months prior to treatment.
• History of hematemesis or hemoptysis (defined as having bright red blood of 1/2 teaspoon or more per episode) less than or equal to 1 month prior to study enrollment.
• Subject has cardiac dysfunction including any of the following:

Sponsors & Collaborators

• Morphotek: lead
• SCRI Development Innovations, LLC: collaborator

Study Sites (2)

Unknown Facility

Oklahoma City, Oklahoma, United States

Location

Unknown Facility

Nashville, Tennessee, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Pancreatic Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 3, 2013
• First Posted: January 4, 2013
• Study Start: June 19, 2013
• Primary Completion: February 9, 2016
• Study Completion: February 9, 2016
• Last Updated: March 29, 2024
• Results First Posted: March 29, 2024

Record last verified: 2017-02

Locations

US (2)