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A Phase 1 Study to Evaluate the Safety and Pharmacokinetic Profile of CBLB502 in Patients With Advanced Cancers

Phase 1
18 Years
Open (Enrolling)
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase 1 Study to Evaluate the Safety and Pharmacokinetic Profile of CBLB502 in Patients With Advanced Cancers


I. To determine the safety, tolerability, and maximum tolerated dose (MTD) of CBLB502
(entolimod) in patients with advanced cancers.


I. To assess any preliminary evidence of efficacy with the CBLB502 in patients with advanced

II. To evaluate pharmacokinetic (PK)/pharmacodynamic (PD) profiles of CBLB502 in patients
with advanced cancers.

III. To characterize the effect, if any, of subcutaneous CBLB502 on QTcB.


I. To correlate pre-treatment tissue expression of toll-like receptor 5 (TLR5) with clinical
activity (Response Evaluation Criteria In Solid Tumors [RECIST] tumor response) and PD
response (as measured by cytokine levels) of CBLB502.

OUTLINE: This is a dose-escalation study.

Patients receive entolimod subcutaneously (SC) daily for 3 days. Treatment repeats every
6-12 weeks for up to 2-3 courses in the absence of disease progression or unacceptable

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

- Written informed consent granted prior to initiation of any study-specific screening
procedures, given with the understanding that the patient has the right to withdraw
from the study at any time, without prejudice

- Histologically or cytologically confirmed locally advanced, inoperable or metastatic
solid tumor for which no acceptable therapy exists

- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Life expectancy greater than 3 months

- Platelet count >= 75 x 10^9/L

- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

- Hemoglobin (Hgb) >= 9 gm/dL

- Total bilirubin =< 1.5 x upper limit of normal (ULN)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN,
regardless of the presence of liver metastases

- Creatinine =< 2 x ULN

- Left ventricular ejection fraction (LVEF) >=45% by echocardiogram (ECHO) or multi
gated acquisition scan (MUGA)

- 12-Lead Electrocardiogram (ECG) with normal tracing or non-clinically significant
changes that do not require medical intervention

- QTcB interval < 470 msec at any point prior to receiving the first dose of study drug
(mean of replicate values, correction per institutional standard) and no history of
Torsades des Pointes or other symptomatic QTcB abnormality

- Absence of orthostatic hypotension

Exclusion Criteria:

- Male and female subjects of child-bearing potential who do not agree to use
double-barrier contraceptive measures, oral contraception, or avoidance of
intercourse during the study and for 90 days after last investigational drug dose

- Previous anti-cancer chemotherapy, immunotherapy or investigational agents =< 3 weeks
prior to the first day of study defined treatment; palliative radiation < 2 weeks;
patients who receive gamma knife radiosurgery for brain metastases are eligible if
procedure was performed > 2 weeks before treated is started, is clinically stable and
is not receiving corticosteroid therapy; ongoing hormonal therapies (such as,
luteinizing hormone-releasing hormone [LHRH] antagonists, megestrol, anti-estrogens,
or aromatase inhibitors) are allowed

- Previous treatment with a TLR5 agonist

- Patients with a known hypersensitivity to CBLB502 or to its excipients

- Presence of neutralizing antibodies to CBLB502

- Patient has a history of cardiac dysfunction including any of the following:

- Myocardial infarction within the last 6 months, documented by persistent
elevated cardiac enzymes; patients with persistent regional wall abnormalities
on assessment of LVEF function are not eligible

- History of documents congestive heart failure (New York Heart Association [NYHA]
functional classification III-IV) within 6 months

- Documented cardiomyopathy

- Diagnosed or suspected congenital QT syndrome

- Any history of second or third degree heart block (may be eligible if currently
have a pacemaker)

- Heart rate < 50 beats/minute on pre-entry electrocardiogram

- Uncontrolled hypertension defined as systolic blood pressure > 160 mm Hg on 3
consecutive measurements prior to study enrollment

- Active clinically serious infections defined as >= Grade 2 according to National
Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version

- Substance abuse, medical, psychological, or social conditions that may, in the
opinion of the Investigator, interfere with the patient's participation in the study
or evaluation of the study results

- Any condition that is unstable or which could jeopardize the safety of the patient
and his/her protocol compliance

- Known infection with human immunodeficiency virus (HIV) or hepatitis B or hepatitis C

- Patients who have been treated with any hematopoietic colony-stimulating growth
factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to
starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2
weeks prior to enrollment, may be continued

- Women who are pregnant or breast feeding

- Patients receiving chronic treatment with steroids or another immunosuppressive
agent; Note: topical applications (e.g., rash), inhaled sprays (e.g., obstructive
airways diseases), eye drops or local injections (e.g., intra-articular) are allowed

- Uncontrolled diabetes mellitus defined as a HgbA1c > 7%

- Patients who have received chemotherapy or targeted anticancer therapy =< 3 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must
recover a Grade 1 toxicity before starting the trial

- Patient is unable or unwilling to abide by the study protocol or cooperate fully with
the investigator

Type of Study:


Study Design:

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

Outcome Measure:

MTD of entolimod

Outcome Description:

Evaluated using NCI-CTCAE Version 4.0.

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Alex Adjei

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Food and Drug Administration

Study ID:

I 196111



Start Date:

January 2012

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific



Roswell Park Cancer Institute Buffalo, New York  14263