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A Phase I Study of the Safety, Tolerability, and PK of MORAb-066, a Humanized Monoclonal Antibody to Human TF, in Patients With Advanced or Metastatic Breast, Pancreatic, Colorectal, or NSCLC (Adenocarcinoma) Malignancies

Phase 1
18 Years
Open (Enrolling)
Breast Cancer, Pancreatic Cancer, Colorectal Cancer, Non-small-cell Lung Cancer, NSCLC, Adenocarcinoma

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Trial Information

A Phase I Study of the Safety, Tolerability, and PK of MORAb-066, a Humanized Monoclonal Antibody to Human TF, in Patients With Advanced or Metastatic Breast, Pancreatic, Colorectal, or NSCLC (Adenocarcinoma) Malignancies

Primary Objective

• To evaluate the safety and tolerability of weekly intravenous (IV) infusions of MORAb-066.

Secondary Objectives

- To identify the dose-limiting toxicities (DLT) and to determine the maximum tolerated
dose (MTD) of MORAb-066.

- To characterize the pharmacokinetic (PK) properties of MORAb-066.

- To identify, on the basis of safety, PK, and pharmacodynamics (PDx) data, a recommended
Phase II dose and schedule for MORAb-066.

- To make a preliminary assessment of the antitumor activity of MORAb-066.

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- To detect any antibody response (i.e., human antihuman antibodies [HAHA]) to multiple
IV infusions to MORAb-066.

Exploratory Objectives

- To evaluate the presence of tissue factor (TF) substrates such as protease activated
receptor 2 when applicable.

- To evaluate the archived tumor tissue for TF overexpression by immunohistochemistry.

- To evaluate whether there are potential biomarkers that correlate responses to

Inclusion Criteria:

- Patients must meet the following criteria in order to be included in this clinical

1. Histologically or cytologically confirmed diagnosis of breast, colorectal,
pancreas, or NSCLC (adenocarcinoma) that is metastatic or unresectable for which
there is no effective therapy.

2. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
(see Appendix A).

3. Measurable disease according to Response Evaluation Criteria in Solid Tumors
(RECIST) v1.1.

4. Subject has recovered (to Grade ≤ 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).

5. Adequate organ system function ≤2 weeks prior to Day1, defined as follows:

- Absolute neutrophil count (ANC) ≥1.5 x 109/L

- Platelets ≥100 x 109/L

- Hemoglobin ≥9 g/dL

- Prothrombin time/partial thromboplastin time (PT/PTT) within institutional
limits of normal

- Serum total bilirubin ≤1.5 times the upper limit of normal (ULN)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x
ULN if no liver involvement or ≤5 x ULN with liver involvement.

- Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥50 mL/min
as calculated by the Cockcroft-Gault method, OR 24-hour measured urine
creatinine clearance ≥50 mL/min.

6. Life expectancy of ≥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 ≥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

Exclusion Criteria:

- Patients who meet any of the following criteria will be excluded from trial entry:

1. Patients currently receiving cancer therapy (i.e., chemotherapy, radiation
therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor

2. 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

3. Any major surgery, chemotherapy, radiotherapy, or immunotherapy within the last
21 days (limited palliative radiation is allowed ≥2 weeks).

4. Subject has received wide field radiotherapy (including therapeutic
radioisotopes such as strontium 89) ≤ 28 days or limited field radiation for
palliation ≤ 14 days prior to starting study drug or has not recovered from side
effects of such therapy.

5. Known intracranial involvement, leptomeningeal metastases or spinal cord
compression due to disease.

6. Known allergy or hypersensitivity to monoclonal antibodies.

7. 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.

8. Known prior significant bleeding history.

9. Patients with ureteral stents or 3+ blood in the urine at baseline.

10. Patients who are receiving chronic systemic anticoagulation therapy (warfarin
sodium or heparin, etc.).

11. Patients who received a previous mAb therapy and have evidence of an immune or
allergic reaction or previously documented HAHA reaction.

12. A serious non-healing wound, active ulcer, or untreated bone fracture. An
abdominal fistula or gastrointestinal perforation <6 months prior to treatment.

13. History of hematemesis or hemoptysis (defined as having bright red blood of 1/2
teaspoon or more per episode) ≤1 month prior to study enrollment.

14. Subject has cardiac dysfunction including any of the following:

- 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 >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

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. Women who are pregnant or lactating.

20. Psychological, familial, sociological, or geographical conditions that do not
permit compliance with the protocol.

21. Concurrent condition that in the investigator's opinion would jeopardize
compliance with the protocol.

22. Inability or unwillingness to comply with study and/or follow-up procedures
outlined in the protocol.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose

Outcome Time Frame:

24 Months

Safety Issue:


Principal Investigator

Johanna Bendell, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sarah Cannon Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

June 2013

Completion Date:

June 2015

Related Keywords:

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



Tennessee Oncology Nashville, Pennsylvania  37203