Safety, PK, PD, and Antitumor Activity of ARQ 531 in Hematologic Malignancies

Conditions:Blood Cancer, Lymphoma, Hematology
Therapuetic Areas:Hematology, Oncology
Age Range:18 - Any
Start Date:July 10, 2017
End Date:April 2019
Contact:ArQule, Inc.

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A Phase 1 Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of ARQ 531 in Selected Subjects With Relapsed or Refractory Hematologic Malignancies

This Phase 1 dose escalation study will evaluate the safety, pharmacology, and activity of
ARQ 531 in subjects with relapsed or refractory hematologic malignancies dosed orally once
per day beginning at 5 mg/dose for 4 weeks with the following cohorts treating at escalating
doses until a dose limiting toxicity or a recommended Phase 2 dose (RP2D) is reached.

During the dose escalation period, intra-subject dose escalation will be permitted if the
following criteria are met:

1. The next higher dose for the regimen has demonstrated to be safe by at least 3 subjects
and the last subject completed one cycle without experiencing any dose limiting toxicity

2. The subject who will receive the dose escalation has not experienced a DLT.

Once the RP2D is determined, expanded cohorts studying specific malignancies (e.g., B-cell
NHL, WM, CLL) at the RP2D will be opened to further explore the safety, pharmacology, and
activity of ARQ 531 as monotherapy.

Inclusion Criteria:

1. Signed written informed consent granted prior to initiation of any study-specific

2. 18 years of age and older.

3. Relapsed or refractory SLL/CLL, WM, B-cell NHL who have received at least 2 prior
lines of systemic therapy.

4. Prior therapy must include a BTK inhibitor in diseases for which approved therapy
includes a BTK inhibitor (i.e., SLL/CLL, WM, and mantle cell lymphoma). Subjects with
DLBCL must have failed, refused, or be ineligible for autologous stem cell transplant.
Subjects with low grade lymphoma must be progressing and requiring treatment.

5. Disease status requirement:

1. For CLL subjects, symptomatic disease that mandates treatment (Halleck et al.

2. For B-cell NHL subjects, measurable disease by imaging scan.

3. For WM, serum immunoglobulin M (IgM) with a minimum IgM level of ≥ 2 times the
upper limit of normal (ULN).

6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

7. Good organ function:

1. Creatinine clearance of ≥ 60 mL/min as estimated by the Cockcroft-Gault equation
or by 24 hour urine collection.

2. Total bilirubin ≤ 1.5 × institutional ULN (total bilirubin of ≤ 3 x institutional
ULN in subjects with documented Gilbert's syndrome).

3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ×
institutional ULN.

4. Platelet count ≥ 50,000/µL

5. ANC ≥ 1000/µL

6. Hemoglobin (Hgb) ≥ 8.0 g/dL, stable for ≥ 1 week

8. For men and women of child-bearing potential, willing to use adequate contraception
(e.g., latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire
duration of the study.

9. Female subjects of child-bearing potential must have a negative serum pregnancy test
within 14 days of the first day of drug dosing.

10. Ability to swallow oral medications without difficulty.

Exclusion Criteria:

1. Had immunotherapy, radiotherapy, radioimmunotherapy, biological therapy, chemotherapy,
or treatment with an investigational product within 4 weeks prior to treatment
initiation (or oral therapy within 1 week prior to treatment initiation).

2. Subjects who were intolerant to a BTK inhibitor

3. Subjects currently being treated with a CYP 2C9, CYP 2C8, CYP 2C19, CYP 2D6, and P-gp
substrate with a narrow therapeutic index.

4. Prior allogeneic bone marrow transplant.

5. Active CNS involvement

6. Pregnant or breast-feeding women.

7. Has significant, ongoing, co-morbid conditions which would preclude safe delivery of
the study drug.

8. Uncontrolled illness including but not limited to: ongoing or active infection,
symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or
IV heart failure), unstable angina pectoris, cardiac arrhythmia, cardiac infarction in
the past 6 months, and psychiatric illness that would limit compliance with study

9. QTc prolongation (defined as a QTc > 450 msecs) or other significant ECG abnormalities
including 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, or
bradycardia (ventricular rate less than 50 beats per minute [bpm]). If the screening
ECG has a QTc > 450 msecs, the ECG can be submitted for a centralized, cardiologic

10. Active human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C

11. Other medical or psychiatric illness or organ dysfunction which, in the opinion of the
Investigator, would either compromise the subject's safety or interfere with the
evaluation of the safety of the study agent.

12. History of prior cancer within < 2 years, except for basal cell or squamous cell
carcinoma of the skin, cervical cancer in situ or other in situ carcinomas.
We found this trial at
Columbus, Ohio 43210
Phone: 781-994-0300
Columbus, OH
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3322 West End Avenue
Nashville, Tennessee 37203
(615)329-SCRI (7274)
Phone: 781-994-0300
Sarah Cannon Research Institute Sarah Cannon Research Institute (SCRI) is a global strategic research organization...
Nashville, TN
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Salt Lake City, Utah 84112
Phone: 781-994-0300
Salt Lake City, UT
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