The purpose of this study is to see if the study drug, called TEW-7197, is safe and determine
what the best dose is to treat future patients when given in combination with pomalidomide
(POM). The study will also look to see if it has any effect on multiple myeloma, when given
in combination with POM.
- To determine the maximum tolerated dose (MTD) or maximum tested dose level of TEW-7197
given in combination with pomalidomide (POM) for the treatment of relapsed or relapsed
or refractory multiple myeloma (RRMM)
- To characterize the safety and tolerability profile of TEW-7197 in combination with POM
at the MTD
To evaluate the activity of the combination of TEW-7197/POM regimen in terms of:
- Overall response rate (complete response [CR] + very good partial response [VGPR]
+partial response [PR]) and clinical benefit rate (CR + VGPR + PR + minimal response
[MR]) based on International Myeloma Working Group (IMWG) defined response criteria and
the duration of response (DOR) in RRMM patients.
- Progression-free survival (PFS) and PFS at 6 months (PFS-6)
To evaluate the bone remodeling and immunologic effects of POM/TEW combination therapy and
its correlation with clinical outcome in patients with multiple myeloma.
Study Design To evaluate the bone remodeling and immunologic effects of POM/TEW combination
therapy and its correlation with clinical outcome in patients with multiple myeloma. This
study is a Phase I, open label trial of TEW-7197 in combination with standard doses of POM.
The study will be conducted as a modified Fibonacci 3 + 3 dose escalation design to determine
the MTD of TEW-7197 in combination with standard doses of POM. Patients will receive
combination TEW-7197 /POM.
- Patient has given voluntary written informed consent before performance of any
study-related procedures not part of standard (non-investigational) medical care.
- Patient has been previously diagnosed with multiple myeloma based on standard
- Patient has relapsed or refractory disease according to international uniform response
criteria and must have previously received therapy with:
- A proteasome inhibitor and Immunomodulatory imide drugs (IMiD)
- All subjects must have documented disease progression during or after their last
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2.
- Patient has measurable disease defined as at least one of the following:
- Serum M protein ≥ 0.5 /dL (≥5 g/L)
- Urine M protein ≥ 200 mg/24 hours
- Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and
an abnormal serum FLC ratio (<0.26 or >1.65)
- Clinical Laboratory Inclusion Criteria: The following laboratory results must be met
within 14 days (or as stipulated) prior to study drug (treatment) administration:
- Absolute neutrophil count (ANC) ≥ 1000 cells/μl (growth factor cannot be used
within the previous 5 days)
- Platelet count ≥ 50,000/μl (without platelet transfusion in the previous 5 days)
- Aspartate aminotransferase (AST/SGOT) and Alanine aminotransferase (ALT/SGPT) ≤
3.0 x upper limit of normal (ULN)
- Serum total bilirubin ≤ 2.0 mg/dL or >3.0 x ULN for subjects with hereditary
- Creatinine clearance ≥ 30 ml/min (calculated by the Cockcroft-Gault Equation or
per 24 hour urine collection)
- Serum calcium (corrected for albumin) level at or below the ULN range (treatment
of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to
normal range with standard treatment).
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test prior to initiation of the study treatment with TEW-7197 /POM. The test must have
a sensitivity of at least 50 mIU/mL. Study participants who are FCBP must either
commit to continued abstinence from heterosexual intercourse or begin two acceptable
methods of birth control, one highly effective method and one additional effective
method at the same time, at least 28 days before she starts taking POM through 30 days
after the last dose of POM and 60 days after the last dose of TEW-7197. FCBP must also
agree to ongoing pregnancy testing during the entire duration of treatment. Men must
agree to use a latex or synthetic condom during sexual contact with a FCBP even if
they have had a vasectomy from the time of signing the informed consent form through
60 days after the last dose of POM or TEW-7197. These same patients must not donate
sperm. All patients must be counseled at a minimum of every 28 days about pregnancy
precautions and risks of fetal exposure. All patients enrolled into this trial, must
agree to be registered in and must comply with all requirements of the Pomalidomide
Risk Evaluation and Mitigation Strategy (POM REMS™) program.
- Prior therapy with TEW-7197 or received any investigational drug within the prior 28
- Plasma Cell Leukemia
- Patients with solitary plasmacytoma
- Patients who are primarily eligible for autologous stem cell transplant
- Prior anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, and
immunotherapy) within the prior 21 days except for alkylating agents (e.g., melphalan)
within the prior 28 days.
- Prior treatment with pomalidomide.
- Subjects with active malignancy and/or cancer history that may confound the assessment
of the study endpoints. Patients with a past cancer history (within 2 years of entry)
with substantial potential for recurrence and/or ongoing active malignancy must be
discussed with the trial collaborator, MedPacto Inc., before study entry. Patients
with the following neoplastic diagnoses are eligible: non-melanoma skin cancer,
carcinoma in situ (including superficial bladder cancer), cervical intraepithelial
neoplasia, and organ-confined prostate cancer with no evidence of progressive disease
- Any > grade 1 (according to the National Cancer Institute Common Terminology Criteria
for Adverse Events (NCI CTC AE) v.4.03) adverse reaction unresolved from previous
treatments or not readily managed and controlled with supportive care. The presence of
alopecia of any grade and peripheral neuropathy ≤ Grade 2 without pain is allowed.
- Previous allogeneic stem cell transplantation with active graft versus host disease
(GVHD), or treatment with immunosuppressive therapy in the 2 months prior to study
- No oral corticosteroids 3 days before initiating combinations TEW-7197/POM; inhaled
corticosteroids are permitted.
- Patient is known to be human immunodeficiency virus (HIV) positive, or have chronic or
active Hepatitis B (core- or surface antigen-positive) or active hepatitis C
- Clinically significant cardiovascular disease (e.g., uncontrolled or any New York
Heart Association (NYHA) Class 3 or 4, congestive heart failure, uncontrolled or
unstable angina, history of myocardial infarction or stroke within 6 months prior to
study entry, or clinically significant arrhythmias not controlled by medication).
- Major abnormalities identified by ECG or echocardiogram (ECHO), at the Investigator's
- Presence of aneurisms of the ascending aorta or aortic stress.
- Hypertension that is not controlled by standard medication (to 150/90 mmHg or below).
- Uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive
pulmonary disease (COPD), pulmonary hypertension) that in the opinion of the
investigator would put the patient at significant risk for pulmonary complications
during the study.
- Uncontrolled intercurrent illness including, but not limited to, uncontrolled
infection, disseminated intravascular coagulation (DIC), or psychiatric illness/social
situations that would limit compliance with study requirements.
- History of erythema multiforme or severe hypersensitivity to prior IMiD's such as
thalidomide and lenalidomide.
- Patients requiring hemodialysis
- The patient is receiving medications that are:
- Exclusively or primarily eliminated by cytochrome P-450 isozyme 3A4 (CYP3A4).
- Exclusively or primarily eliminated by Uridine 5'-diphospho
(UDP)-glucuronyltransferase 1A1 (UGT1A1).
- Substrates for the drug transporter multidrug resistance protein 1 (MDR1) have a
narrow therapeutic window; or which are strong inhibitors of drug transporter
- Patients should have discontinued strong CYP1A2 inhibitors (e.g. ciprofloxacin and
fluvoxamine) at least five half-lives before beginning study treatment.
- Inability to tolerate thromboprophylaxis (Required Concurrent Medications)