PK,PD,Safety and Tolerability of Multiple Dose Regimens of MT-3724 With Gemcitabine and Oxaliplatin for the Treatment of Patients With Relapsed/Refractory Diffuse Large B Cell Non-Hodgkin's Lymphoma

Inclusion Criteria: 1. Be adequately informed about the study and fully consent to participation as demonstrated by signing the written informed consent form before any screening procedure. 2. Be aged ≥18 years on the date of signing the informed consent form. 3. Have relapsed or refractory B-cell NHL that, in the investigator's opinion, could benefit from MT-3724+GEMOX therapy. At least one histologically documented relapse of NHL, by: 1. Bone marrow biopsy (FNA is not acceptable) or 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 approved therapies for NHL that are applicable for the patient in the opinion of the treating physician. 1. Patients refractory to treatment are eligible. 2. Patient who have progressed following CAR T-cell therapy are also eligible. 6. Have measurable disease by Lugano Classification for NHL 1. \>1.5 cm longest diameter (LDi) for lymph nodes 2. \>1 cm LDi for extranodal disease 7. Have ECOG performance score of ≤2. 8. Have adequate bone marrow function, as determined by: 1. Absolute neutrophil count (ANC) ≥1,000/mm3 and 2. Platelet count ≥50,000 mm³ 9. Have adequate kidney function, assessed by thecreatinine clearance (CLcr) to be ≥ 50 mL/min either measured or estimated using the Cockcroft-Gault formula. . a. At the investigator's discretion,calculated estimated CLcr of \< 50mL/min may be verified eGFR based on the 24-hour urine collection. Subjects with GFR ≥50 mL/min will be eligible irrespective of the estimated CLcr result. 10. Have adequate hepatic function, as determined by: 1. Total bilirubin ≤1.5 x ULN, or ≤3 x ULN for subjects with Gilbert's Syndrome and 2. Aspartate aminotransferase (AST) ≤3 x ULN (or ≤ 5.0 x ULN if liver involvement) and 3. Alanine aminotransferase (ALT) ≤3 x ULN (or ≤ 5.0 x ULN if liver involvement). 11. Have adequate coagulation, as determined by: 1. INR or PT ≤1.5 x ULN 2. aPTT ≤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 during the screening period within 72 hours before the start of treatment. Women not of reproductive potential are female subjects who are postmenopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy,bilateral salpingectomy). 14. Subjects of reproductive potential and their partners must agree to either to abstain continuously from heterosexual intercourse or to use a reliable birth control method between signing the informed consent until 6 months following the last dose of MT-3724 or GEMOX . The investigator or a designated associate should advise the subject how to achieve adequate contraception. The following birth control methods may be considered as adequate 1. Condoms (male or female) with or without a spermicidal agent; 2. Diaphragm or cervical cap with spermicide; 3. Intrauterine device; 4. Hormone-based contraception: Established use of oral, injected, or implanted hormonal methods of contraception; 5. True abstinence; 6. Vasectomy is an acceptable method for a male subject or male partner of a female subject. Exclusion criteria: 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 other previous cancer curatively treated \>2 years before the start of treatment. 2. Current evidence of new or growing brain or spinal metastases during screening. 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 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. 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. 9. 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. 10. Patients with known active Hepatitis C, HIV or a present history of Hepatitis B 11. Women who are pregnant or breastfeeding 12. History or current evidence of hypersensitivity to any study drugs, or current evidence of hypersensitivity requiring systemic steroid doses ≥20 mg/day Prednisone equivalent 13. Received any amount of anti-CD20 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 the screening period 2. Obinutuzumab (Gazyva®): 184 days 3. Ofatumumab (Arzerra®): 88 days 14. Received therapy for NHL (except anti-CD20 Mab listed above) within 4 weeks before the start of treatment 15. 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 16. 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 discretion after consultation with the Medical Monitor and sponsor. 17. 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 investigator's discretion 18. 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 are permitted. 19. 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, until EoT Visit