PK, PD, Safety, Tolerability of Multiple Dose Regimens of MT-3724 for the Treatment of Patients With Relapsed Non-Hodgkin's B-Cell Lymphoma and B-Cell Chronic Lymphocytic Leukemia

This is a two-part study intended to provide investigators and sponsor with the following
information regarding the investigational new drug MT-3724:

Part 1[COMPLETED]: in patients with relapsed/refractory non-Hodgkin's B cell lymphoma
(including SLL) OR relapsed/refractory B-cell CLL

1. The maximum dose of a single course of MT-3724 given as intravenous (IV) infusions on
Days 1, 3, 5, 8, 10 and 12 at which there are negligible side effects and/or at which
maximum serum levels and/or at which maximum effect on blood lymphocytes are observed.
Six dose levels will be investigated.

2. The changes in MT-3724 serum levels and blood lymphocytes over time following IV doses
at different points in the study.

3. The changes and kinds of clinical and laboratory effects and side effects that may occur
over repeated courses of MT-3724.

4. The changes in each subject's immune status and their non-Hodgkin's lymphoma following
one or more cycles of 6 infusions.

Part 2: An expansion of the maximum tolerated dose cohort in patients with
relapsed/refractory diffuse large B-cell lymphoma (DLBCL)

1. Identify the frequency of nature of clinical and laboratory adverse events that may
occur over repeated courses of MT-3724 at the maximum tolerated dose.

2. Define the PK and PD profiles of MT-3724 at the maximum tolerated dose.

Inclusion Criteria:

- Men or women, age 18 years or older

Part 1:

- Histologic diagnosis of B-Cell NHL. Histology based upon bone marrow biopsies and/or
fine needle aspirates as the sole means of diagnosis are not acceptable. All patients
must have measurable disease. Any tumor mass of at least 1.5 cm is acceptable.

- Presence of lymphadenopathy and/or splenomegaly with histopathological evaluation of a
lymph node biopsy consistent with CLL. Clonality of the circulating B-lymphocytes
should be confirmed at screening. Previously confirmed immunohistological diagnosis
with a characteristic CD5+/CD20+ B--cell immunophenotype according to WHO criteria.
CLL diagnosis requires an absolute peripheral blood monoclonal CD20+/CD5+ B-lymphocyte
count ≥ 5000 cells/μL for the duration of at least 3 months.

Part 2:

- Diffuse large B cell lymphoma (DLBCL). Histology based upon bone marrow biopsies
and/or fine needle aspirates as the sole means of diagnosis are not acceptable.

- Subject must have the following staging requirements:

1. CLL (Part 1): Rai Stage III or IV disease, or stage 0-II disease that meets
National Cancer Institute Working Group (NCIWG) criteria for active disease
requiring therapy that may include either of the following disease-related
symptoms:

- Progressive lymphadenopathy including bulky disease as defined by mass,
lymph node or lymph node cluster > 10 cm.

- Progressive lymphocytosis with > 50% increase over a 2-month period, or
anticipated doubling time < 6 months.

2. NHL (Part 1 and 2): Intermediate or high risk by Ann Arbor Staging with Cotswald
Modifications that meets criteria for active disease requiring therapy.

- History of at least one anti-CD20 antibody containing regimen that resulted in initial
measurable response (partial or complete remission), followed by relapse/recurrence.

- Patients must have received all approved therapies known to provide clinical benefit
for their disease subtype and for which they are eligible or must have refused these
treatment options prior to consideration for enrolment. In the case of patients who
have lymphomas for which high-dose chemotherapy and autologous stem cell
transplantation (HD-ASCT) is considered a standard curative therapy, eligibility for
this study requires that the patient's disease has relapsed after HD-ASCT, that the
patient is not eligible for HD-ASCT, or that the patient has refused HD-ASCT.

- Patients with known central nervous system metastases may be enrolled if they have
received radiotherapy, do not require chronic steroid therapy, have had computed
tomography or magnetic resonance imaging of the brain within 1 month of study entry
that shows stable disease and they have no neurological symptoms other than low grade
neuropathy.

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

- Patients must be at least 28 days past their last course of lymphoma or CLL treatment,
at least 84 days past their last course of rituximab treatment. Patients with
pre-existing severe or life threatening side effects/conditions from prior therapy or
due to other diseases may not be enrolled

- Part 2: Subjects who have received any amount of rituximab within 365 days of planned
dose day 1 must have a serum rituximab level of <500 ng/ml documented by the study's
reference laboratory prior to the initiation of dosing. Potential subjects who have
received any other anti CD20 MAb therapy (obinutuzumab, ofatumumab, or ibritumomab
tiuxetan) must be at least 8 half-lives past their last dose prior to initiation of
study drug dosing. Washout periods for these drugs are as follows:

1. obinutuzumab (terminal half-life in NHL = 36.8 days); required washout = 184 days
(26 weeks)

2. ofatumumab (terminal half-life in CLL = 17.6 days); required washout = 88 days
(13 weeks)

3. ibritumomab tiuxetan (biologic half-life in NHL = 1.9 days [based upon
measurement of radioactivity from administered [111In]-ibritumomab tiuxetan];
required washout = 10 days (1.5 weeks)

- Female patients of childbearing potential must have a negative serum or urine
pregnancy test within 3 days prior to initiating dosing. Male and female subjects with
reproductive potential must agree to use acceptable contraceptive methods while on
study therapy and for 12 week following their last dose of study medication.

Exclusion Criteria:

- Patients who cannot comply with protocol requirements including clinic visits for
intravenous infusions and birth control measures may not be enrolled.

- Female patients who are pregnant or are breast feeding.

- Potential patients with a history of another cancer other than basal cell carcinoma or
cervical intraepithelial neoplasia (cervical cancer in situ) may not be enrolled
unless it is documented that their previous cancer was treated, they have been disease
free for five or more years prior to starting this study and they are in their
doctor's judgment at less than 30% risk of relapse of this previous malignancy.

- Patients with a peripheral blood total lymphocyte count of higher than 25,000/mm3 may
not be enrolled.

- Patients cannot have experienced a significant (CTCAE Grade 3 or 4 with or without
neutropenia) infection within 2 weeks of their first dose of MT-3724.

- Patients are not eligible if they are using any other approved or investigational
anti-neoplastic therapies or any other investigational therapies for any other reason.

- Patients may not be receiving systemic corticosteroid therapy at a prednisone dose >
20 mg/day (or steroid equivalent) within 2 weeks of starting study.

- Patients with uncontrolled or severe cardiovascular disease, including myocardial
infarct or unstable angina within 6 months prior to start of study treatment, New York
Heart Association (NYHA) Class II or greater congestive heart failure, serious
arrhythmias requiring medication for treatment, clinically significant pericardial
disease, or cardiac amyloidosis may not be enrolled.

- Patients with a known history of drug abuse or any chronic neurologic, psychiatric,
endocrine, metabolic, immunologic, hepatic or renal disease (including a history of
hemolytic uremic syndrome) that in the opinion of the Investigator would adversely
affect study participation.

- Patients with known active Hepatitis C, HIV or a present history of Hepatitis B

- Patients must not have received any vaccines for 28 days prior to administration of
their first dose of MT-3724 and should not receive any vaccine during the study or
within 28 days after their last dose of MT-3724.

- Patients with a suspected allergy or sensitivity to any component of MT-3724 drug
preparation based upon known allergies to compounds of a similar class who have had an
anaphylactic or other severe infusion reaction to human immunoglobulin or monoclonal
antibody administration are n ot eligible.

- Patients who have had an allogeneic hematopoietic stem cell transplantation are not
eligible.

- Patients who have had major surgery within 6 weeks prior to the first dose of study
drug or have major surgery planned during the first 12 weeks after MT-3724 has
finished.