The purpose of this study is to evaluate the safety and tolerability of MT-3724 in
combination with Lenalidomide in subjects with relapsed or refractory B-Cell NHL.
This is a multi-center, open-label two-part study evaluating the safety and tolerability of
MT-3724 in combination with Lenalidomide in relapsed or refractory 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 Lenalidomide
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 Lenalidomide. In addition, the PK, PD, immunogenicity and tumor response at the MTD of
MT-3724 in combination with Lenalidomide 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
Six 28 day cycles (approximately 6 months)
- Subjects must meet ALL the following criteria to be eligible for the study.
1. Be adequately informed about the study and fully consent to participation as
demonstrated by signing the written informed consent form before any screening
2. Men or Women , age 18 years or older Have relapsed or refractory B-cell NHL that,
in the investigator's opinion, could benefit from MT-3724+LEN therapy.
3. At least one histology documented relapse of NHL by:
1. Bone marrow biopsy (FNA is not acceptable)
2. Excisional lymph node biopsy or
3. Core biopsy of any involved organ (FNA not acceptable)
4. CD20-positive histology must have been confirmed at any time during NHL
disease course and documented in the medical history.
5. If no histology is available after any relapse the investigator can consult
the medical monitor to discuss if the patient can be included
4. All subtypes of B-cell NHL may be considered for Part 1 (MT-3724 dose
escalation). Only histologically documented DLBCL (including mixed histology) may
be considered for Part 2 (expansion cohort)
5. 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.
6. Have measurable disease by Lugano Classification for NHL (see Appendix 4):
1. >1.5 cm longest diameter (LDi) for lymph nodes
2. >1.0 cm LDi for extra nodal disease.
7. Eastern Cooperative Oncology Group (ECOG) performance score of ≤2
8. Have adequate bone marrow function, as determined by all the following:
1. Absolute neutrophil count (ANC) ≥1,000/mm³
2. Platelet count ≥50,000 mm³
9. Have adequate kidney function, assessed by the estimated glomerular filtration
rate (eGFR) ≥60 mL/min calculated by the CPK-EPI equation.
a. At the investigator's discretion, the eGFR result <60 mL/min may be verified
by measurement of creatinine clearance (CLcr) based on the 24-hour urine
collection. Subjects with CLcr ≥60 mL/min will be eligible irrespective of the
10. Have adequate hepatic function, as determined by:
1. Total bilirubin ≤1.5 x ULN, or ≤3 x ULN for subjects with Gilbert's
2. AST ≤3 x ULN and
3. ALT ≤3 x ULN
11. Have adequate coagulation, as determined by:
1. INR or PT ≤1.5 x ULN
2. PTT ≤1.5 x ULN
12. Have adequate serum albumin, as determined by:
a. Albumin ≥ 3.0 g/dL
13. Women of reproductive potential must have a negative pregnancy test on 2
occasions during the screening period (within 10-14 days and within 24 hours
before the start of treatment). Women not of reproductive potential are female
subjects who are postmenopausal or permanently sterilized (e.g., hysterectomy,
14. Males must agree to always use a latex or synthetic condom during any sexual
contact with females of reproductive potential while taking LEN and for up to 4
weeks after discontinuing LEN, even if they have undergone a successful
vasectomy. Male patients taking LEN must not donate sperm.
15. Subjects of reproductive potential and their partners must agree to either to
abstain continuously from heterosexual intercourse or to use 2 methods of
reliable birth control simultaneously to begin 4 weeks prior to initiating
treatment with LEN until 28 days after the last dose of MT-3724 or LEN. The
investigator or a designated associate should advise the subject how to achieve
adequate contraception. The following birth control methods may be considered:
one highly effective form of contraception - tubal ligation, IUD, hormonal (birth
control pills, injections, hormonal patches, vaginal rings, or implants), or
partner's vasectomy, and one additional effective contraceptive method - male
latex or synthetic condom, diaphragm, or cervical cap.
- Subjects who meet any of the following criteria must be excluded from the study.
Medical and surgical history
1. 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 previous cancer
curatively treated >2 years before the start of treatment.
2. Current evidence of new or growing brain or spinal metastases during screening.
Subjects with known brain or spinal metastases may be eligible if they
1. Had radiotherapy or another appropriate therapy for the brain or spinal
2. Have no neurological symptoms (excluding Grade ≤2 neuropathy)
3. Have stable brain or spinal disease on the CT or MRI scan within 1 month of
4. Do not require chronic steroid therapy
3. History of allogeneic hematopoietic stem cell transplant within 180 days before the
start of treatment.
4. Current evidence of acute or chronic Graft versus Host Disease.
5. Current evidence of CTCAE Grade >1 toxicity (except for hair loss, and those
toxicities listed in other eligibility criteria) before the start of treatment.
6. Current evidence of incomplete recovery from surgery before the start of treatment, or
planned surgery at any time during the study until the EoT Visit, except minor
elective interventions deemed acceptable by the investigator.
7. History or current evidence of significant (CTCAE Grade ≥2) infection or wound within
4 weeks before the start of treatment.
8. History or current evidence of significant cardiovascular disease including, but not
limited to the following conditions:
1. Unstable angina (symptoms of angina at rest) or new-onset angina within ≤3 months
before the start of treatment.
2. Arterial thrombosis or pulmonary embolism within ≤3 months before the start of
3. Myocardial infarction or stroke within ≤3 months before the start of treatment.
4. Pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade ≥2), non
malignant pleural effusion (CTCAE Grade ≥2) or malignant pleural effusion (CTCAE
5. Congestive heart failure (NYHA Class III or IV) at screening or LVEF <45%,
assessed by Echo or MUGA scan within 1 month before starting study treatment.
(Echo or MUGA scan performed within 6 months before screening and at least 28
days after the last cancer therapy is acceptable provided the subject has not
received any potential cardiotoxic agents).
6. Cardiac arrhythmia requiring anti-arrhythmic therapy at screening. Subjects
receiving digoxin, calcium channel blockers, or beta-adrenergic blockers are
eligible at the investigator's discretion after consultation with Medical Monitor
if the dose has been stable for ≥2 weeks before the start of treatment. Subjects
with sinus arrhythmia and infrequent premature ventricular contractions are
eligible at the investigator's discretion.
9. QTcF (Fridericia) >480 ms, determined as the average from three QTcF values on the
triplicate ECG obtained at screening.
10. Current evidence of seropositive status for HIV, hepatitis B (positive for HBsAg or
anti-HBsAg and anti-HBcAg antibodies) or hepatitis C (positive for anti-HCV antibody
or HCV-RCV-RNA quantitation) as assessed by the applicable serology testing at
1. Serology testing is not required if seronegativity is documented in the medical
history and there are no clinical signs suggestive of HIV or hepatitis infection.
2. Subjects with positive HBV serology are eligible if quantitative PCR for plasma
HBV-DNA is negative and the subject will be receiving prophylaxis for potential
3. Subjects with positive HCV serology are eligible if quantitative PCR for plasma
HCV RNA is negative.
11. Women who are pregnant or breastfeeding.
12. History or current evidence of hypersensitivity to any of the study drugs, or of
current hypersensitivity requiring systemic steroids at doses >20 mg/day prednisone
13. History or current evidence of any other medical or psychiatric condition or addictive
disorder, or laboratory abnormality that, in the opinion of the investigator, may
increase the risks associated with study participation, or require treatments that may
interfere with the conduct of the study or the interpretation of study results.
14. Received anti-CD20 monoclonal antibody (Mab) therapy within the following periods
before the start of treatment
1. Rituximab (Rituxan®): 84 days; if a subject had received rituximab within 37
Weeks before the start of treatment, then a serum rituximab level must be
negative (<500 ng/mL) at screening.
2. Obinutuzumab (Gazyva®): 184 days
3. Ofatumumab (Arzerra®): 88 days
15. Received therapy for NHL (except the anti-CD20 Mab therapies listed above) within 4
weeks before the start of treatment.
16. Any investigational drug treatment from 4 weeks or 5 half-lives of the agent before
the start of treatment, whichever is longer, until the EoT Visit.
17. 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.
a. Palliative radiotherapy to non-target lesions is allowed at the investigator's
18. Received any vaccines within 28 days of the start of treatment, or likely to require
vaccines at any time from the start of treatment until 28 days after the last dose of
MT-3724. Injectable flu vaccine (inactivated or recombinant) is permitted at the
19. Received systemic immune modulators within 2 weeks before the start of treatment
1. Systemic immune modulators include but are not limited to systemic
corticosteroids at doses >20 mg/day of prednisone equivalent, cyclosporine and
2. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is permitted