Inclusion Criteria Part 1 (RRMM patients only)

• Confirmed diagnosis of MM per the revised IMWG diagnostic criteria
• Patients with RRMM who have failed treatment with, are intolerant to, or are not candidates for available therapies that are known to confer clinical benefit
• Must meet all of the following criteria for prior therapy:
  • Must be refractory to ≥1 proteasome inhibitor (PI), ≥1 immunomodulatory drug (IMiD), and ≥1 steroid
  • Must either have received ≥3 prior lines of therapy or ≥2 prior lines of therapy if 1 line included a combination of PI and IMiD (prior treatment with an anti-CD38 therapy is permitted)
• With measurable disease, defined as ≥1 of the following:
  • Serum M-protein ≥500 mg/dL (≥5 g/L) on serum protein electrophoresis (SPEP).
  • Urine M-protein ≥200 mg/24 h on urine protein electrophoresis (UPEP).
  • Serum FLC assay result with an involved FLC level ≥10 mg/dL (≥100 mg/L) if serum FLC ratio is abnormal.
• Patients with serum M-protein, urine M-protein, or involved immunoglobulin FLC not meeting the measurable disease criteria above will be eligible if they have ≥1 of the following:
  • Bone marrow (BM) aspirate/biopsy with plasma cell percentage ≥30%
  • PET imaging with ≥1 plasmacytoma lesion with a single diameter of ≥2cm.
• With Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
• With normal QT interval corrected by the Fridericia method (QTcF) on screening electrocardiogram (ECG)[ QTcF of ≤450 millisecond (ms) in males or ≤470 ms in females]
• Must meet the following clinical laboratory criteria at entry:
  • Total bilirubin ≤1.5*the upper limit of the normal range (ULN), except for Gilbert's syndrome (direct bilirubin must be <2.0*ULN)
  • Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤2.5*ULN.
  • Estimated glomerular filtration rate (eGFR) ≥30 (mL/min/1.73 square meter [m2]), using the modification of diet in renal disease (MDRD) equation
  • Absolute neutrophil count (ANC) ≥1000 per cubic millimeter (/mm3) (≥1.0*109 per liter [/L]); ≥750/mm3 (≥0.75*109/L) may be acceptable for participants with >50% of plasma cells in BM
  • Platelet count ≥75,000/ mm3 (≥75*109/L); ≥50,000/ mm3 (≥50*109/L) may be acceptable for participants with >50% of plasma cells in BM
  • Hemoglobin ≥7.5 g/dL without transfusion within 7 days before the lab test.
  • Serum albumin ≥2.5 g/dL.
• Female patients who:
  • are postmenopausal for at least 1 year prior to screening OR
  • are surgically sterile OR
  • If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective barrier method at the same time from study entry through 30 days after the last dose of study drug OR
  • agree to practice true abstinence if in line with the preferred and usual lifestyle [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable. Female and male condoms should not be used together]
• Male patients, even if surgically sterilized (postvasectomy) who:
  • Agree to practice effective barrier contraception during the entire study and through 90 days after the last dose of study drug OR
  • Agree to practice true abstinence if in line with the preferred and usual lifestyle [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods. Female and male condoms should not be used together]

Inclusion criteria Part 2 (both RRMM and RRNHL patients)

• ECOG performance score of 0 or 1.
• Normal QTcF on screening ECG, defined as QTcF of ≤450 ms in males or ≤470 ms in females
• Must meet the following clinical laboratory criteria at study entry:
  • Total bilirubin ≤1.5*the ULN, except for Gilbert's syndrome (direct bilirubin must be <2.0*ULN)
  • Serum ALT and AST ≤2.5*ULN
  • eGFR ≥30 mL/min/1.73 m2(MDRD equation)
  • ANC ≥1000 mm3 (≥1.0*109 /L); a count of ≥750/mm3 (≥0.75*109/L) may be acceptable for participant with >50% of plasma cells in BM
  • Platelet count ≥75,000/ mm3 (≥75*109/L); a value of ≥50,000/ mm3(≥50*109/L) may be acceptable for participants with >50% of plasma cells in BM
  • Hemoglobin ≥7.5 g/dL without transfusion within 7 days before the lab test
  • Serum albumin ≥2.5 g/dL
• Female patients who:
  • are postmenopausal for at least 1 year prior to screening OR
  • are surgically sterile OR
  • If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective barrier method at the same time from study entry through 30 days after the last dose of study drug OR
  • agree to practice true abstinence if in line with the preferred and usual lifestyle [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable. Female and male condoms should not be used together]
• Male patients, even if surgically sterilized (postvasectomy) who:
  • Agree to practice effective barrier contraception during the entire study and through 90 days after the last dose of study drug OR
  • Agree to practice true abstinence if in line with the preferred and usual lifestyle [periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable. Female and male condoms should not be used together] Inclusion Criteria Part 2 for RRNHL patients
• Pathologically confirmed diagnosis of the following NHL subtype based on local pathology report:
  • Mantle cell lymphoma (MCL) i. Nodal MCL
  • Diffuse large B-cell lymphoma (DLBCL) i. DLBCL-NOS ii. Plasmablastic lymphoma (PbL) iii. Primary effusion lymphoma (PEL). iv. Primary effusion lymphoma (PMBL)
  • Follicular lymphoma
  • Burkitt lymphoma (BL)
  • Peripheral T-cell lymphoma (PTCL) i. PTCL-NOS (eligible at MTD/RPTD if biopsy evidence of CD38 positivity) ii. Angioimmunoblastic T-cell lymphoma (AITL)
  • Extranodal NK/T-cell lymphoma (ENKTL)-nasal type
• RRNHL, having failed treatment with, is intolerant to, or is determined not to be a candidate for available therapies considered standard of care (SOC) or are known to confer clinical benefit.
  • At least 1 measurable site of disease according to the Lugano classification for lymphoma.
  • A measurable nodal lesion with longest diameter (LDi) greater than 1.5cm OR
• A measurable extranodal lesion with LDi greater than 1.0cm
• Evidence of a CD38 positive tumor. Any of the following are acceptable:
  • Evidence of CD38 expression from most recent biopsy or blood sample [either flow cytometry (FCM) or immunohistochemistry (IHC)] OR
  • The most recently archived tissue assessed for CD38 expression by IHC OR
  • Fresh biopsy for CD38 expression assessment by IHC within 35 days of Cycle 1 Day 1 OR
  • Fresh blood sample with circulating NHL cells assessed by FCM within 35 days of Cycle 1 Day 1 (BM biopsy excisional lymph node biopsy, core biopsy of any involved organ are all acceptable methods, find needle aspirate is not. Any level of positive CD38 expression is eligible) Inclusion Criteria Part 2 for RRMM patients
• Confirmed diagnosis of MM per IMWG diagnosis criteria:
• RRMM, having failed treatment with, is intolerant to, or is determined not to be a candidate for available therapies considered SOC or are known to confer clinical benefit.
• Must meet the following criteria for prior therapy:
  • Refractory or intolerant to ≥1 PI and ≥1 IMiD
  • Receipt of ≥3 prior lines of therapy or ≥2 prior lines of therapy if 1 of those lines included a combination of a PI or IMiD (prior treatment with anti-CD38 therapy is permitted except for patients enrolled in the anti-CD38 therapy naïve cohort)
  • Daratumumab RR cohorts: RR to daratumumab at any time during treatment. Patients RR to other anti-CD38 therapies are excluded.
  • Anti-CD38 therapy naïve cohort: must not have received any prior anti CD-38 therapy.
• Measurable disease, defined as ≥1 of the following
  • Serum M-protein ≥50 mg/dL (≥5 g/L) on SPEP.
  • Urine M-protein ≥200 mg/24 hours on UPEP.
  • Serum FLC assay result with and involved FLC level ≥10 mg/dL (≥100mg/L), provided the serum FLC ratio is abnormal.
• Serum M-protein, urine M-protein or involved immunoglobulin FLC not meeting measurable disease criteria if at least 1 of the following criteria is met:
  • BM aspirate/biopsy showing plasma cell percentage ≥30%
  • PET imaging showing at least 1 plasmacytoma lesion with a single diameter ≥2 cm.

Exclusion Criteria for Part 1 (RRMM patients only):

• With polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, or Immunoglobulin M (IgM) myeloma.
• With sensory or motor neuropathy of NCI CTCAE V5 Grade ≥3.
• Have received final dose of any of the following treatments/procedures within the following interval before the first dose of MT-0169:
  • Myeloma-specific therapy, including PIs and IMiDs: 14 days
  • Anti-CD38 (a) therapy: Isatuximab 90 days; daratumumab 60 days
  • Corticosteroid therapy for myeloma: 7 days
  • Radiation therapy for localized bone lesions: 14 days
  • Major surgery:30 days
  • Autologous stem cell transplant: 90 days
  • Investigational therapy: 30 days
• Have received an allogeneic stem cell transplant or organ transplantation.
• Have not recovered to Grade ≤1 or baseline, from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia and Grade 2 neuropathy.
• With clinical signs of central nervous system (CNS) involvement of MM.
• With a history of myelodysplastic syndrome or another malignancy other than MM except for the following: any malignancy that has been in complete remission for 3 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, or asymptomatic prostate cancer without known metastatic disease and not requiring therapy or requiring only hormonal therapy and with normal prostate-specific antigen level for ≥1 year before the start of study therapy.
• With known or suspected light chain amyloidosis of any organ (amyloid on the BM biopsy without other evidence of amyloidosis is acceptable).
• With any of the following cardiovascular conditions:
  • Congestive heart failure (NYHA) class ≥II or left ventricular ejection fraction (LVEF <40%, cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris or myocardial infarction or clinically significant arrhythmia requiring therapy including anticoagulants within the past 6 months or at screening
  • Resting tachycardia (heart rate of > 100 bpm) at screening
  • Clinically significant uncontrolled hypertension at screening
  • Cardiac MRI at screening demonstrates evidence of infiltrative disease of the myocardium
• With a history of document significant pleural or pericardial effusions within 3 months before the start of treatment, including:
• a) Pericarditis (any Grade) b) Pericardial effusion (Grade ≥2) c) Non-malignant pleural effusion (Grade ≥2) d) Malignant pleural effusion (Grade ≥2)
• Patients with a history of noncardiogenic pulmonary edema associated with diffuse peripheral edema and a history of intravascular hypovolemia associated with systemic antineoplastic therapy.
• With chronic or active infection requiring systemic therapy, history of symptomatic viral infection that has not been fully cured.
• a) With HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts ≥350 cells/mL may be allowed but patient must be taking appropriate opportunistic infection prophylaxis if clinically relevant b) With positive HBV serology may be allowed if undetectable viral load, receiving antiviral prophylaxis for potential HBV reactivation per institutional guidelines c) With positive HCV serology may be allowed if quantitative PCR for plasma HCV RNA is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed.
• Have received a live attenuated vaccine within 28 days of first dose of MT-0169.
• With a history of ≥ Grade 2 systemic inflammatory response syndrome (SIRS)/ cytokine release syndrome (CRS) reactions following infusion with any monoclonal antibodies or Chimeric Antigen Receptor (CAR) T therapy
• With a chronic condition requiring systemic corticosteroids at >10 mg/day of prednisone or equivalent.
• Are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or patients of reproductive potential who are not employing an effective birth control
• With a concurrent medical or psychiatric illness that would preclude study conduct and assessment including, but not limited to, uncontrolled medical conditions, uncontrolled and active infection, uncontrolled risk of bleeding, uncontrolled diabetes mellitus, pulmonary disease, alcoholic liver disease, or primary biliary cirrhosis.
• With known allergy or intolerance to any of the drugs used in the study or excipients in the MT-0169 formulation.
• With a history of hypersensitivity or serious toxic reaction to kanamycin or another aminoglycoside.

Exclusion Criteria for Part 2 RRMM patients only:

• With POEMS syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, IgM myeloma.
• Have received a final dose of any of the following treatments/procedures within the following interval before the first dose of MT-0169:
  • Myeloma-specific therapy, including PIs and IMiDs: 14 days
  • Anti-CD38 therapy - Isatuximab: 90 days
  • Anti-CD38 therapy - Daratumumab: 60 days
  • Corticosteroid therapy for myeloma: 7 days
  • Radiation therapy for localized bone lesions: 14 days
  • Major surgery: 30 days
  • Autologous stem cell transplant: 90 days
  • Investigational therapy: 30 days
• Have received an allogenic stem cell or organ transplant.
• With clinical signs of CNS involvement of MM.
• With a history of myelodysplastic syndrome or another malignancy other than MM except or any malignancy in complete remission for 3 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, or asymptomatic prostate cancer without known metastatic disease and not requiring therapy or requiring only hormonal therapy and with normal prostate-specific antigen level for >1 year before the start of study therapy.
• With known or suspected light chain amyloidosis of any organ (amyloid on BM biopsy without other evidence of amyloidosis is acceptable).

Exclusion Criteria for Part 2 (both RRMM and NHL patients):

• Failed to recover to Grade ≤1 or baseline from adverse reactions to prior treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia and stable Grade 2 neuropathy.
• With any of the following cardiovascular conditions:
  • Congestive heart failure (NYHA) class ≥II LVEF <40%, cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris or myocardial infarction or clinically significant arrhythmia requiring therapy including anticoagulants within the past 6 months or at screening
  • Resting tachycardia (heart rate of >100 bpm) at screening
  • Clinically significant uncontrolled hypertension at screening
  • Cardiac MRI at screening demonstrating infiltrative disease of the myocardium
• With a history of documented significant pleural or pericardial effusions, specifically any of the following within 3 months before the start of study treatment:
  • a) Pericarditis (any grade) b) Pericardial effusion (Grade ≥2) c) Non-malignant pleural effusion (Grade ≥2) OR d) Malignant pleural effusion (Grade ≥3)
• With a history of noncardiogenic pulmonary edema associated with peripheral edema and a history of intravascular hypovolemia associated with antineoplastic therapy.
• With chronic or active infection requiring systemic therapy and a history of symptomatic viral infection that is not fully controlled or cured. The following exceptions apply for those with positive serologies of HIV, HBV, or HCV:
  • With HIV and undetectable viral load and CD4+ T-cell (CD4+) counts ≥350 cells/mL may be enrolled, but must be taking appropriate opportunistic infection prophylaxis, if clinically relevant.
  • With positive HBV serology are eligible if they have an undetectable viral load and the patient will receive antiviral prophylaxis for potential HBV reactivation per institutional guidelines.
  • With positive HCV serology are eligible if qPCR for plasma HCV RNA is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed.
  • Have received a live attenuated vaccine within 28 days of the first dose of MT-0169
  • With a history of Grade ≥2 SIRS/CRS reactions following infusion with any mAbs or CAR T therapy.
  • With a chronic condition requiring systemic corticosteroids ≥10 mg/day of prednisone or equivalent.
  • With a known allergy or intolerance to any of the drugs in the study or excipients in the MT-0169 formulation.
  • Are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or male or female patients of reproductive potential who are not employing effective birth control.
  • With a concurrent medical or psychiatric illness that would preclude study conduct and assessment including, but not limited to, uncontrolled medical conditions, uncontrolled and active infection, uncontrolled risk of bleeding, uncontrolled diabetes mellitus, pulmonary disease, alcoholic liver disease, or primary biliary cirrhosis.
  • With a history of hypersensitivity or serious toxic reactions to kanamycin or another aminoglycoside