The drug being tested in this study is called MT-0169. The study will evaluate the safety,
tolerability, preliminary efficacy, PK, pharmacodynamics, and immunogenicity of MT-0169
monotherapy in participants with RRMM or RRNHL.
This study is conducted in 2 parts. The study will enroll up to 144 total participants (up to
54 participants in Part 1 and up to 90 participants in Part 2).
Part 1 (Dose Escalation): The purpose of Part 1 is to evaluate the safety and tolerability of
MT-0169 in subjects with relapsed or refractory multiple myeloma (RRMM) and relapsed or
refractory non-Hodgkin lymphoma (RRNHL) and to estimate the maximum tolerated dose (MTD) or
the recommended Phase 2 dose (RP2D).
Part 2 (Dose Expansion): The purpose of Part 2 is to confirm the RP2D and to evaluate the
preliminary clinical activity of MT-0169 monotherapy in patients with RRMM and RRNHL.
MT-0169 will be given as an intravenous (IV) infusion over 60 minutes on the same day every
week (i.e., days 1, 8, 15 and 22) or every 2 weeks (i.e., days 1 and 15) of each cycle. A
cycle is defined as 28 days.
In Parts 1 and 2, a subject may participate for the following three (3) periods:
Screening Period - up to 28 days before first dose of MT-0169 Treatment Period - active
period where a subject will receive doses of MT-0169 over a 28-day treatment period Follow-up
Period - up to 12 months after the last patient in the study to receive the last dose of
MT-0169.
In both parts of the study, participants can receive MT-0169 until the cancer worsens, side
effects prevent further study treatment, or until the participant leaves the study for other
reasons decided by the participant, the study doctor, or the sponsor of the study. After
treatment has finished, participants will have a check-up of their disease status every 12
weeks.
This multi-center trial will be conducted worldwide. The overall duration of the study will
vary for each participant because they will receive study treatment until unacceptable
toxicity, withdrawal of consent, death, termination of the study by the sponsor, or
fulfillment of another discontinuation criterion. Participants will be followed up for 30
days after the last dose of study drug for a follow-up assessment for any side effects.
Participants will then be followed every 12 weeks to check for the status of their disease up
to 12 months after the last subject on the trial has the last dose of study drug, or the
sponsor discontinues the study, whichever occurs first.
Inclusion Criteria Part 1 (RRMM patients only)
1. Confirmed diagnosis of MM per revised IMWG diagnostic criteria
2. 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
3. Must meet all of the following criteria for prior therapy:
1. Must be refractory to â¥1 proteasome inhibitor (PI), â¥1 immunomodulatory drug
(IMiD), and â¥1 steroid
2. Must either have received â¥3 prior lines of therapy or â¥2 prior lines of therapy
if 1 line included a combination of PI and IMiD (prior treatment with anti-CD38
therapy is permitted).
4. With measurable disease, defined as â¥1 of the following:
1. Serum M-protein â¥500 mg/dL (â¥5 g/L) on serum protein electrophoresis (SPEP).
2. Urine M-protein â¥200 mg/24 h on urine protein electrophoresis (UPEP).
3. Serum FLC assay result with an involved FLC level â¥10 mg/dL (â¥100 mg/L) if serum
FLC ratio is abnormal.
5. 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 â¥1 of the
following:
1. Bone marrow (BM) aspirate/biopsy with plasma cell percentage â¥30%
2. PET imaging with â¥1 plasmacytoma lesion with a single diameter of â¥2cm.
6. With Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
7. With normal QT interval corrected by the Fridericia method (QTcF) on screening
electrocardiogram (ECG)[ QTcF of â¤450 millisecond (ms) in males or â¤470 ms in females]
8. Must meet the following clinical laboratory criteria at entry:
1. Total bilirubin â¤1.5*the upper limit of the normal range (ULN), except for
Gilbert's syndrome (direct bilirubin must be <2.0*ULN)
2. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) â¤2.5*ULN.
3. Estimated glomerular filtration rate (eGFR) â¥30 (mL/min/1.73 square meter [m2]),
using the modification of diet in renal disease (MDRD) equation
4. Absolute neutrophil count (ANC) â¥1000 per cubic millimeter (/mm3) (â¥1.0*109 per
liter [/L]); â¥750/mm3 (â¥0.75*109/L) may be acceptable for participants with >50%
of plasma cells in BM
5. Platelet count â¥75,000/ mm3 (â¥75*109/L); â¥50,000/ mm3 (â¥50*109/L) may be
acceptable for participants with >50% of plasma cells in BM
6. Hemoglobin â¥7.5 g/dL without transfusion within 7 days before the lab test.
7. Serum albumin â¥2.5 g/dL.
9. Female patients who:
1. are postmenopausal for at least 1 year prior to screening OR
2. are surgically sterile OR
3. 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
4. agree to practice true abstinence if in line with the preferred, 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]
10. Male patients, even if surgically sterilized (postvasectomy) who:
1. Agree to practice effective barrier contraception during the entire study and
through 90 days after last dose of study drug OR
2. Agree to practice true abstinence if in line with the preferred, 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 (both RRMM and RRNHL patients)
1. ECOG performance score of 0 or 1.
2. Normal QTcF on screening ECG, defined as QTcF of â¤450 ms in males or â¤470 ms in
females
3. Must meet the following clinical laboratory criteria at study entry:
1. Total bilirubin â¤1.5*the ULN, except for Gilbert's syndrome (direct bilirubin
must be <2.0*ULN)
2. Serum ALT and AST â¤2.5*ULN
3. eGFR â¥30 mL/min/1.73 m2(MDRD equation)
4. ANC â¥1000 mm3 (â¥1.0*109 /L); a count of â¥750/mm3 (â¥0.75*109/L) may be acceptable
for participant with >50% of plasma cells in BM
5. Platelet count â¥75,000/ mm3 (â¥75*109/L); a value of â¥50,000/ mm3(â¥50*109/L) may
be acceptable for participants with >50% of plasma cells in BM
6. Hemoglobin â¥7.5 g/dL without transfusion within 7 days before the lab test
7. Serum albumin â¥2.5 g/dL
4. Female patients who:
1. are postmenopausal for at least 1 year prior to screening OR
2. are surgically sterile OR
3. 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 last dose of study drug OR
4. agree to practice true abstinence if in line with the preferred, 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]
5. Male patients, even if surgically sterilized (postvasectomy) who:
1. Agree to practice effective barrier contraception during the entire study and
through 90 days after the last dose of study drug OR
2. 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
6. Pathologically confirmed diagnosis of the following NHL subtype based on local
pathology report:
1. Mantle cell lymphoma (MCL) i. Nodal MCL
2. Diffuse large B-cell lymphoma (DLBCL) i. DLBCL-NOS ii. Plasmablastic lymphoma
(PbL) iii. Primary effusion lymphoma (PEL). iv. Primary effusion lymphoma (PMBL)
3. Follicular lymphoma
4. Burkitt lymphoma (BL)
5. Peripheral T-cell lymphoma (PTCL) i. PTCL-NOS (eligible at MTD/RPTD if biopsy
evidence of CD38 positivity) ii. Angioimmunoblastic T-cell lymphoma (AITL)
6. Extranodal NK/T-cell lymphoma (ENKTL)-nasal type
7. 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.
8. At least 1 measurable site of disease according to the Lugano classification for
lymphoma.
1. A measurable nodal lesion with longest diameter (LDi) greater than 1.5cm OR
2. A measurable extranodal lesion with LDi greater than 1.0cm
9. Evidence of a CD38 positive tumor. Any of the following are acceptable:
1. Evidence of CD38 expression from most recent biopsy or blood sample [either flow
cytometry (FCM) or immunohistochemistry (IHC)] OR
2. The most recently archived tissue assessed for CD38 expression by IHC OR
3. Fresh biopsy for CD38 expression assessment by IHC within 35 days of Cycle 1 Day
1 OR
4. 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). Fine needle aspirate may be accepted on
a case-by-case basis after discussion with the medical monitor of the sponsor.
Inclusion Criteria Part 2 for RRMM patients
1. Confirmed diagnosis of MM per IMWG diagnosis criteria:
2. 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.
3. Must meet the following criteria for prior therapy:
1. Refractory or intolerant to â¥1 PI and â¥1 IMiD
2. Receipt of â¥3 prior lines of therapy or â¥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)
3. Daratumumab RR cohorts: RR to daratumumab at any time during treatment. Patients
RR to other anti-CD38 therapies are excluded.
4. Anti-CD38 therapy naïve cohort: must not have received any prior anti CD-38
therapy.
4. Measurable disease, defined as â¥1 of the following
1. Serum M-protein â¥50 mg/dL (â¥5 g/L) on SPEP.
2. Urine M-protein â¥200 mg/24 hours on UPEP.
3. Serum FLC assay result with and involved FLC level â¥10 mg/dL (â¥100mg/L), provided
the serum FLC ratio is abnormal.
5. 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:
1. BM aspirate/biopsy showing plasma cell percentage â¥30%
2. PET imaging showing at least 1 plasmacytoma lesion with a single diameter â¥2 cm.
Exclusion Criteria for Part 1 (RRMM patients only):
1. 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.
2. With sensory or motor neuropathy of NCI CTCAE V5 Grade â¥3.
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
4. Have received an allogeneic stem cell transplant or organ transplantation.
5. Have not recovered to Grade â¤1 or baseline, from adverse reactions to prior myeloma
treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding
alopecia and Grade 2 neuropathy.
6. With clinical signs of central nervous system (CNS) involvement of MM.
7. With a history of myelodysplastic syndrome or another malignancy other than MM except
for the following: 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 â¥1 year before the start of study
therapy.
8. With known or suspected light chain amyloidosis of any organ (amyloid on the BM biopsy
without other evidence of amyloidosis is acceptable).
9. With any of the following cardiovascular conditions:
1. Congestive heart failure (NYHA) class â¥II or left ventricular ejection fraction
(LVEF <40%, cardiac myopathy, active ischemia, or any other uncontrolled cardiac
condition or myocardial infarction or clinically significant arrhythmia requiring
therapy including anticoagulants within the past 6 months or at screening
2. Resting tachycardia (heart rate of > 100 bpm) at screening
3. Clinically significant uncontrolled hypertension at screening
4. Cardiac MRI at screening demonstrates evidence of infiltrative disease of the
myocardium
10. With a history of document significant pleural or pericardial effusions within 3
months before the start of treatment, including:
1. Pericarditis (any Grade)
2. Pericardial effusion (Grade â¥2)
3. Non-malignant pleural effusion (Grade â¥2)
4. Malignant pleural effusion (Grade â¥2)
11. Patients with a history of noncardiogenic pulmonary edema associated with diffuse
peripheral edema and history of intravascular hypovolemia associated with systemic
antineoplastic therapy.
12. With chronic or active infection requiring systemic therapy, history of symptomatic
viral infection that has not been fully cured.
1. With HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts â¥350
cells/mL may be allowed but patient must be taking appropriate opportunistic
infection prophylaxis if clinically relevant
2. With positive HBV serology may be allowed if undetectable viral load, receiving
antiviral prophylaxis for potential HBV reactivation per institutional guidelines
3. 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.
13. Have received a live attenuated vaccine within 28 days of first dose of MT-0169.
14. 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
15. With a chronic condition requiring systemic corticosteroids at >10 mg/day of
prednisone or equivalent.
16. 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
17. With a concurrent medical or psychiatric illness that would preclude study conduct and
assessment including, but not limited to, uncontrolled medical conditions, active
infection, risk of bleeding, diabetes mellitus, pulmonary disease, alcoholic liver
disease, or primary biliary cirrhosis.
18. With known allergy or intolerance to any of the drugs used in the study or excipients
in MT-0169
19. With a history of hypersensitivity or serious toxic reaction to kanamycin or another
aminoglycoside.
Exclusion Criteria for Part 2 NHL patients only:
1. With known CNS lymphoma (exception if history of CNS disease and evidence of SD on
neuroimaging separated by at least 4 weeks and within 4 weeks of Cycle 1 Day 1)
2. Have received a final dose of any of the following treatments/procedures within the
following minimum interval before the first dose of MT-0169:
- Nitrosoureas: 6 weeks
- Chemotherapy: 4 weeks
- Small molecules (<0.9 kDa): 5 half-lives or at least 2 weeks
- Therapeutic antibodies: 4 weeks
- Radio/toxin -immunoconjugates: 12 weeks
- Radiation therapy - target lesion (measurable disease): 4 weeks
- Radiation therapy - nontarget lesion: 2 weeks
- Investigational chemotherapeutic agents or antibodies: 4 weeks
- Daratumumab: 60 days
- Isatuximab: 90 days
- (MCL) Bruton's tyrosine kinase inhibitors: 2 weeks or 5 half-lives, whichever is
longer
- Major surgery (determined by the principal investigator and Sponsor): 4 weeks
- Autologous stem cell transplant: 100 days
- Allogenic stem cell transplant: 180 days (patients with graft vs host disease >
Grade 1 will be excluded)
3. With a history of myelodysplastic syndrome or malignancy (other than NHL) except for
the following: 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 â¥1 year before the start of study therapy
Exclusion Criteria for Part 2 RRMM patients only:
4. With POEMS syndrome, monoclonal gammopathy of unknown significance, smoldering
myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, IgM
myeloma.
5. 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
6. Have received an allogenic stem cell or organ transplant.
7. With clinical signs of CNS involvement of MM.
8. 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.
9. 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):
10. Failed to recover to Grade â¤1 or baseline from adverse reactions to prior treatment or
procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia and
stable Grade 2 neuropathy.
11. With any of the following cardiovascular conditions:
1. Congestive heart failure (NYHA) class â¥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
2. Resting tachycardia (heart rate of >100 bpm) at screening
3. Clinically significant uncontrolled hypertension at screening
4. Cardiac MRI at screening demonstrating infiltrative disease of the myocardium
12. With a history of documented significant pleural or pericardial effusions,
specifically any of the following within 3 months before the start of study treatment:
1. Pericarditis (any grade)
2. Pericardial effusion (Grade â¥2)
3. Non-malignant pleural effusion (Grade â¥2) OR
4. Malignant pleural effusion (Grade â¥3)
13. With a history of noncardiogenic pulmonary edema associated with peripheral edema and
a history of intravascular hypovolemia associated with antineoplastic therapy.
14. 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:
1. With HIV and undetectable viral load and CD4+ T-cell (CD4+) counts â¥350 cells/mL
may be enrolled, but must be taking appropriate opportunistic infection
prophylaxis, if clinically relevant.
2. 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.
3. 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.
15. Have received a live attenuated vaccine within 28 days of the first dose of MT-0169
16. With a history of Grade â¥2 SIRS/CRS reactions following infusion with any mAbs or CAR
T therapy.
17. With a chronic condition requiring systemic corticosteroids â¥10 mg/day of prednisone
or equivalent.
18. With a known allergy or intolerance to any of the drugs in the study or excipients in
the MT-0169 formulation.
19. 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.
20. 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.
21. With a history of hypersensitivity or serious toxic reactions to kanamycin or another
aminoglycoside