A Phase 1 Dose Escalation Study of ARQ 621 in Adult Patients With Metastatic Solid Tumors and Hematologic Malignancies

Inclusion Criteria:

- Signed written informed consent must be obtained and documented according to
International Conference on Harmonisation (ICH)- Good Clinical Practice (GCP), the
local regulatory requirements, and permission to use private health information in
accordance with the Health Insurance Portability and Accountability Act (HIPPA) prior
to study-specific screening procedures

- A histologically or cytologically confirmed metastatic solid tumor or
refractory/relapsed hematologic malignancy

- Have a life expectancy of at least 12 weeks

- ≥18 years of age

- Measurable disease as defined by:

- Solid Tumors: Response Evaluation Criteria in Solid Tumors

- Multiple Myeloma (MM): International Uniform Response Criteria, at least one of
the following:

- Monoclonal protein in the plasma of ≥0.5 g/dL

- Monoclonal protein in the urine of ≥0.2 g/24 hr urine collection

- Serum immunoglobulin free light chain (FLC) ≥100 mg/L (10 mg/dL) and
abnormal serum immunoglobulin kappa to lambda FLC ratio

- Malignant Lymphoma (ML): International Working Group Response Criteria

- At least one site of disease ≥2 cm in longest diameter (a lesion ≥1 cm can
be considered if PET positive)

- Chronic Lymphocytic Leukemia (CLL): NCI Working Group Guidelines

- Lymphocytosis (5 x 10^9 /L) with B-cell marker (CD19, CD20,CD23) + CD5

- High-risk characteristics (hemoglobin <10g/dL OR platelets <100 x 10^9 /L)

- Acute Myelogenous Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL): only
patients with bone marrow or peripheral blast count of ≥20%

- Acute Promyelocytic Leukemia (APML): patients must be refractory to all-trans
retinoic acid (ATRA) and arsenic trioxide

- Chronic Myelogenous Leukemia (CML): patients in blast crisis (bone marrow or
peripheral blast count ≥20%) may be included if refractory to prior therapy and
to any therapy the investigators deems of higher priority (for example, BCR-ABL
inhibitors such as imatinib mesylate [Gleevec], nilotinib [Tasigna], or
dasatinib [Sprycel])

- ECOG performance status ≤2

- Male or female patients of child-producing potential must agree to use contraception
or avoidance of pregnancy measures during the study and for 30 days after the last
ARQ 621 dose

- Females of childbearing potential must have a negative serum pregnancy test

- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × upper limit of
normal (ULN) or ≤5.0 × ULN with metastatic liver disease

- Hemoglobin (Hgb) ≥10 g/dL (except in cases considered related to hematologic
malignancy)

- Total bilirubin ≤1.5 × ULN

- Creatinine ≤1.5 x ULN (≤2.0 x ULN in cases considered related to multiple myeloma)

- Absolute neutrophil count ≥1.5 x 10^9/L (except in cases considered related to
hematologic malignancy)

- Platelets ≥100 x 10^9/L (except in cases considered related to hematologic
malignancy)

- Patients with hematologic malignancies who have progressed following at least two
prior treatment regimens

Exclusion Criteria:

- Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents
within four weeks of the first dose

- In cases of hematologic malignancies, 4-week recovery from prior anticancer
treatment is not required, however the patient must recover from prior
treatment-related non-hematological toxicities to grade 2 or less

- When required for supportive care corticosteroids or hydroxyurea may be used

- Surgery within four weeks prior to the first dose

- Known untreated brain metastases or leptomeningeal disease

- Patients with solid tumors who were treated for brain metastases and who have
shown stable disease for at least 8 weeks prior to enrollment will be allowed

- Pregnant or breastfeeding

- Uncontrolled concurrent illness including, but not limited to ongoing or active
symptomatic infection requiring systemic therapy, clinically significant non-healing
or healing wounds, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or
mild exertion), uncontrolled infection or psychiatric illness/social situations that
would limit compliance with study requirements

- Patients having a history of Thrombotic thrombocytopenic purpura (TTP) or
Hemolytic-uremic syndrome (HUS) or HUS spectrum will be excluded from the study