The purpose of this study is to evaluate the safety and tolerability of MT-3724 in
combination with gemcitabine and oxaliplatin (GEMOX) in subjects with relapsed or refractory
CD20-positive B-Cell NHL.
This is a multi-center, open-label two-part study evaluating the safety and tolerability of
MT-3724 in combination with GEMOX in relapsed or refractory CD20 positive B-cell Lymphoma
Part 1: (MT-3724 Dose Escalation) Define the maximum tolerated dose (MTD) of MT-3724 in
combination with standard treatment of GEMOX
Part 2: (MTD Expansion Cohort) Confirm the safety and tolerability of the MTD of MT-3724 from
Part 1 in the MTD Expansion Cohort, where MT-3724 will be given at the MTD in combination
with GEMOX. In addition, the PK, PD, immunogenicity and tumor response at the MTD of MT-3724
in combination with GEMOX will be more thoroughly evaluated in Part 2.
It is anticipated that up to 64 patients will be enrolled. Treatment will continue for up to
four 28 day cycles (approximately 4 months).
1. Men or Women, age 18 years or older
2. Histology based upon bone marrow biopsies and/or fine needle aspirates as the sole
means of diagnosis are not acceptable. All subtypes of CD20-positive B-cell NHL may be
considered for Part 1 (MT-3724 dose escalation). Only CD20-positive DLBCL may be
considered for Part 2 (expansion cohort)
3. Intermediate or high risk by Ann Arbor Staging with Cotswold Modifications that meets
criteria for active disease requiring therapy.
4. Subjects must have received all available approved therapies for NHL. Those subjects
who are ineligible for approved therapies in the opinion of the investigator, or have
refused such therapies, will be eligible.
5. Measurable disease (≥1 cm) by Lugano Classification for NHL.
6. Eastern Cooperative Oncology Group (ECOG) performance score of ≤2.
7. Female patients of childbearing potential must have a negative serum or urine
pregnancy test within 7 days prior to initiating dosing. Male and female subjects with
reproductive potential must agree to use acceptable contraceptive methods until the
end of study visit.
- Patients who cannot comply with protocol requirements including clinic visits for
intravenous infusions and birth control measures may not be enrolled.
- History or current evidence of neoplastic disease that is histologically distinct from
NHL except cervical carcinoma in situ, superficial noninvasive bladder tumors,
curatively treated Stage I-II non-melanoma skin cancer, or any other previous cancer
curatively treated >2 years before the start of treatment.
- Current evidence of new or growing brain or spinal metastases during screening.
- History of allogeneic hematopoietic stem cell transplant within 180 days before the
start of treatment.
- Current evidence of acute or chronic Graft versus Host Disease.
- Current evidence of CTCAE Grade >1 toxicity (except for hair loss, and those
toxicities listed in other eligibility criteria) before the start of treatment.
- Current evidence of incomplete recovery from surgery before the start of treatment, or
planned surgery at any time until the Last Study Assessment Visit, except minor
elective interventions deemed acceptable by the investigator.
- History or current evidence of significant (CTCAE Grade ≥2) infection or wound within
4 weeks before the start of treatment.
- 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
- Women who are pregnant or breastfeeding.
- History or current evidence of hypersensitivity to components of the investigational
product or significant (CTCAE Grade ≥2) allergy to any other allergen.
- Received any amount of anti-CD20 MAb therapy within the following periods before the
start of treatment
1. Rituximab (Rituxan®): 110 days; if a subject had received rituximab within
111-365 days before the start of treatment, then a serum rituximab level must be
documented to be <500 ng/mL during the screening period
2. Obinutuzumab (Gazyva®): 184 days
3. Ofatumumab (Arzerra®): 88 days
- Received therapy for NHL (except anti-CD20 Mab listed above) within 3 weeks or 5
half-lives of the agent before the start of treatment, whichever is longer.
- Received radiotherapy to tumor lesions that would be chosen as target lesions
(measurable disease) within 4 weeks before the start of treatment, unless the lesion
exhibited objective progression between the radiotherapy and the screening according
to the Lugano Classification for NHL.
- Palliative radiotherapy to non-target lesions is allowed at the investigator's
discretion after consultation with the Medical Monitor and sponsor.
- Received systemic immune modulators within 2 weeks before the start of treatment
including but not limited to systemic corticosteroids >20 mg/day of prednisone
equivalent, cyclosporine and tacrolimus. Corticosteroids for pre-medication and NSAIDs
- Received any investigational drug treatment within 4 weeks or within 5 half-lives of
the therapeutic agent before the start of treatment, whichever is longer.