| Eligibility |
Inclusion Criteria:
- Participants 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 ICF before any screening procedure.
2. Be aged =18 years years on the date of signing the informed consent form.
3. Have relapsed or refractory CD20 positive B-cell NHL that, in the investigator's
opinion, could benefit from MT-3724+LEN therapy. Participants must have proof of CD20
positive NHL either by:
1. Historical biopsies (obtained with diagnosis of relapsed or refractory disease),
or
2. Fresh biopsies.
- Bone marrow biopsy
- Excisional lymph node biopsy
3. Core biopsy of any involved organ; all are acceptable methods; FNA not acceptable
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 (MTD expansion cohort).
5. Have received all available approved therapies for NHL, one of which should be
anti-CD20 based therapy.
1. Participants whose prior therapy includes chimeric antigen receptor t-cell
(CAR-T) cell therapy are eligible.
2. Participants who underwent stem cell transplant (SCT) >100 days for autologous
SCT or >180 days for allogeneic SCT before study drug administration and
exhibited a full hematological recovery (consistent with the existing inclusion
criteria requirements and without PRBC or platelet transfusions within 2 weeks of
C1D1) prior to relapse are eligible.
6. Have bi-dimensionally measurable disease by Lugano Classification for NHL:
1. >1.5 cm LDi for lymph nodes
2. >1.0 cm LDi for extra nodal disease.
7. Eastern Cooperative Oncology Group (ECOG) performance status 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
3. Hemoglobin =8g/dL
9. Have adequate kidney function, creatinine clearance (CLcr) to be =50mL/min either
measured or assessed by using the Cockcroft-Gault formula.
a. At the investigator's discretion, the eGFR result =50 mL/min may be verified by
measurement of CLcr based on the 24-hour urine collection. Participants with CLcr =50
mL/min will be eligible irrespective of the eGFR result.
10. Have adequate hepatic function, as determined by:
1. Total bilirubin =1.5 x upper limit normal (ULN), or direct bilirubin =1.5 x ULN
for participants with elevated total bilirubin secondary to Gilbert's Syndrome)
and
2. Aspartate aminotransferase (AST) =3 x ULN (or =5 x ULN if liver involvement) and
3. Alanine aminotransferase (ALT) =3 x ULN (or =5 x ULN if liver involvement)
11. Have adequate coagulation, as determined by:
1. International Normalized Ration (INR) or Prothrombin Time (PT) =1.5 x ULN (unless
on therapeutic anticoagulants)
2. Activated partial thromboplastin time (aPTT) =1.5 x ULN (unless on therapeutic
anticoagulants)
12. 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 participants who are
postmenopausal(>1 year since last menstrual cycle) or permanently sterilized (e.g.,
hysterectomy, bilateral salpingectomy).
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
participants taking LEN must not donate sperm.
15. Participants 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 participants how to achieve adequate contraception. The
following birth control methods may be considered: one highly effective form of
contraception - tubal ligation, intrauterine device (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.
16. Participants must have a life expectancy of >3 months from the start of treatment.
Exclusion Criteria:
- Participants 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. Participants with prior,
curatively treated cancer >2 years ago before the start of treatment can be enrolled.
2. Current evidence of new or growing brain or spinal metastases during screening.
Participants with known brain or spinal metastases may be eligible if they:
1. Had radiotherapy or another appropriate therapy for the brain or spinal
metastases; concurrent prophylactic treatment is allowed.
2. Neurological symptoms must be stable and no worse than grade 2
3. Have evidence of stable brain or spinal disease on computer topography (CT) or
magnetic resonance imaging (MRI) scan obtained within 4 weeks of signing the ICF
and compared with prior imaging results.
4. Do not require chronic steroid therapy, or if applicable, have been stable on
steroid dose of no more than prednisone 20mg/day or equivalent by C1D1.
3. Current evidence of Graft versus Host Disease.
4. Current evidence of Common Terminology Criteria for Adverse Events (CTCAE) Grade >1
toxicity (before the start of treatment, except for hair loss, and those Grade 2
toxicities listed as permitted in other eligibility criteria).
5. Current evidence of incomplete recovery from surgery or radiotherapy before the start
of treatment, or planned surgery or radiotherapy at any time during the study until
the EoT Visit, except minor elective interventions deemed acceptable by the
investigator.
6. Current evidence of significant (CTCAE Grade =2) infection or wound within 4 weeks
before the start of treatment.
a. Participants with Grade 2 infection that has stabilized or improved with oral
anti-infectives before the start of treatment may be eligible at the sponsor's
discretion
7. 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
treatment.
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
Grade =3).
5. Congestive heart failure New York Heart Association (NYHA) Class III or IV at
screening or left ventricular ejection fraction (LVEF) <45%, assessed by Echo or
multiple-gated acquisition (MUGA) scan within 1 month before starting study
treatment. (inclusion of participants with LVEF between 40%-45% should be
discussed and approved by the sponsor). Echo or MUGA scan performed within 6
months before screening and at least 28 days after the last cancer therapy is
acceptable provided the participant has not received any potential cardiotoxic
agents since then.
6. Cardiac arrhythmia requiring anti-arrhythmic therapy at Screening. Participants
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 with
MT-3724. Participants with sinus arrhythmia and infrequent premature ventricular
contractions are eligible at the investigator's discretion.
8. QT interval corrected according to Fridericia's formula (QTcF) >480 ms, determined as
the average from three QTcF values on the triplicate electrocardiogram (ECG) obtained
at Screening.
9. Current evidence of uncontrolled HIV, HBV or HCV at screening. Serology testing is not
required if seronegativity is documented in the medical history and if there are no
clinical signs suggestive of HIV or hepatitis infections, or suspected exposure. The
following exceptions apply for participants with positive viral serology:
1. Participants with HIV and an undetectable viral load and CD4+ T-cells counts =350
cells/microliter may be enrolled, but must be taking appropriate opportunistic
infection prophylaxis, if clinically relevant.
2. Participants with positive HBV serology are eligible if they have an undetectable
viral load and the participant will receive antiviral prophylaxis for potential
HBV reactivation-per institutional guidelines.
3. Participants with positive HCV serology are eligible if quantitative PCR for
plasma HCV RNA is below the lower limit of detection. Concurrent antiviral HCV
treatment per institutional guidelines is allowed.
10. Women who are pregnant or breastfeeding.
11. 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
equivalent.
12. 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.
Prior treatments
13. Prior treatment with MT-3724.
14. Received anti-CD20 monoclonal antibody (Mab) therapy within the following periods
before the start of treatment
1. Rituximab (Rituxan® RTX): 84 days; if a participant had received RTX within 37
Weeks before the start of treatment, then a serum RTX 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 and
radioimmunoconjugates) 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 may be permitted at the
investigator's discretion after consultation with the medical monitor.
18. Received any live vaccines within 4 weeks before of the start of treatment, unless the
investigator believes the benefits outweigh the risks, after approval with the
sponsor.
19. Require use of systemic immune modulators during study treatment. a. Systemic immune
modulators include but are not limited to systemic corticosteroids at doses >20 mg/day
or prednisone equivalent, cyclosporine and tacrolimus.
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