A Study of MT-0169 in Participants With Relapsed or Refractory Multiple Myeloma or Non-Hodgkin Lymphoma

• ClinicalTrials.gov Identifier: NCT04017130
• Recruitment Status: Recruiting
• First Posted: July 12, 2019
• Last Update Posted: September 8, 2022
• Sponsor: Molecular Templates, Inc.
• Information provided by (Responsible Party): Molecular Templates, Inc.

Study Description

Brief Summary:

This will be a Phase 1 Open-Label, dose escalation and expansion study of MT-0169 (an Engineered toxin body (ETB) in patients with relapsed or refractory multiple myeloma or non-Hodgkin lymphoma. MT-0169 is an investigational drug that recognizes and binds to the CD38 receptor, which may be found on the surface of multiple myeloma and non-Hodgkin lymphoma cancer cells. It delivers a dose of a modified toxin that kills these cells.

Condition or disease	Intervention/treatment	Phase
Relapsed and/or Refractory Multiple Myeloma; Relapsed and/or Refractory Non Hodgkin Lymphoma	Drug: MT-0169	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 144 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 1, Open-Label, Dose-Escalation and Expansion, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of MT-0169 in Patients With Relapsed or Refractory Multiple Myeloma or Non-Hodgkin Lymphoma
• Actual Study Start Date: February 5, 2020
• Estimated Primary Completion Date: January 17, 2024
• Estimated Study Completion Date: December 17, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1: Dose Escalation; Weekly Dosing Intravenous (IV) infusion of MT-0169 every 7 days: Days 1, 8, 15, and 22 in a 28-day treatment cycle. Every 2 Weeks IV infusion of MT-0169 every 14 days: Days 1 and 15 in a 28-day treatment cycle with escalating doses starting at the MTD/RP2D determined by the weekly dose escalation cohort. Patients will continue to receive treatment until progressive disease, unacceptable toxicity or withdraw from the study for other reasons. Decision to escalate/deescalate/stay on the same dose/discontinue MT-0169 will be based on number of DLTs per number of patients enrolled at each dose level as predetermined by the mTPI-2 statistical model. Subsequent doses will be determined by the frequency and severity of adverse events in previous cohorts. The investigator and sponsor review of available safety, PK, pharmacodynamics, and efficacy data in the previous cohorts will also be factored in the decision.	Drug: MT-0169; MT-0169 intravenous infusion.
Experimental: Part 2: Dose Expansion in patients with RRNHL: Weekly Dosing; This cohort will receive intravenous infusion of MT-0169 every 7 days on Days 1, 8, 15, and 22 in a 28- days treatment cycle. The dose administered will be the MTD/RP2D in the Weekly Dose Escalation of Part 1.	Drug: MT-0169; MT-0169 intravenous infusion.
Experimental: Part 2: Dose Expansion in Patients with RRMM who are also Daratumumab RR: Weekly Dosing; This cohort will receive intravenous infusion of MT-0169 every 7 days on Days 1, 8, 15, and 22 in a 28- days treatment cycle. The dose administered will be the MTD/RP2D in the Weekly Dose Escalation of Part 1.	Drug: MT-0169; MT-0169 intravenous infusion.
Experimental: Part 2: Dose Expansion in Patients with RRMM who are Anti-CD38 Therapy naïve: Weekly Dosing; This cohort will receive intravenous infusion of MT-0169 every 7 days on Days 1, 8, 15, and 22 in a 28- days treatment cycle. The dose administered will be the MTD/RP2D in the Weekly Dose Escalation of Part 1.	Drug: MT-0169; MT-0169 intravenous infusion.
Experimental: Part 2: Dose Expansion in patients with RRNHL: Every 2 Weeks; This cohort will receive intravenous infusion of MT-0169 every 14 days on Days 1 and 15 in a 28- days treatment cycle. The dose administered will be the MTD/RP2D in the Biweekly Dose Escalation of Part 1.	Drug: MT-0169; MT-0169 intravenous infusion.
Experimental: Part 2: Dose Expansion in Patients with RRMM who are also Daratumumab RR: Every 2 Weeks; Each cohort will receive intravenous infusion of MT-0169 every 14 days on Days 1 and 15 in a 28- days treatment cycle. The dose administered will be the MTD/RP2D in the Biweekly Dose Escalation of Part 1.	Drug: MT-0169; MT-0169 intravenous infusion.

Outcome Measures

Primary Outcome Measures :

1. Part 1: maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) [ Time Frame: Up to 12 months ]
2. Part 1: number of participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Up to 12 months ]
3. Part 1: number of participants with Dose-limiting Toxicities (DLTs) [ Time Frame: Up to 12 months ]
4. Part 1:number of participants with Grade greater than or equal to (>=) 3 TEAEs according to NCI CTCAE 5.0 [ Time Frame: Up to 12 months ]
5. Part 1:number of participants with Serious Adverse Events (SAEs) [ Time Frame: Up to 12 months ]
6. Part 1: number of participants who discontinued MT-0169 due to TEAEs [ Time Frame: Up to 12 months ]
7. Part 1: number of participants with treatment-related dose modifications [ Time Frame: Up to 12 months ]
   Dose modifications include dose delays, dose interruptions, and dose reductions
8. Part 2: overall response rate (ORR) for RRMM patients [ Time Frame: Up to 12 months ]
   Percentage of participants who achieved PR or better during study as defined by IMWG Uniform Response Criteria.
9. Part 2: ORR for RRNHL patients [ Time Frame: Up to 12 months ]
   Percentage of participants who achieved PR or better during study as defined by IMWG Uniform Response Criteria.

Secondary Outcome Measures :

1. Part 1 and Part 2, Cmax: maximum observed concentration for MT-0169 [ Time Frame: Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days) ]
2. Part 1 and Part 2, Tmax: time to reach maximum observed concentration for MT-0169 [ Time Frame: Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days) ]
3. Part 1 and Part 2, AUClast: Area Under the Concentration-time Curve From Time 0 to the time of the last quantifiable concentration for MT-0169 [ Time Frame: Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days) ]
4. Part 1: overall response rate (ORR) [ Time Frame: Up to 12 months ]
   As defined by IMWG Uniform Response Criteria for RRMM patients or defined by the Lugano classification for lymphoma for RRNHL patients.
5. Part 1 and Part 2: Clinical Benefit Rate (CBR) for RRMM patients [ Time Frame: Up to 12 months ]
   Percentage of participants who achieved PR or better during study as defined by IMWG Uniform Response Criteria and ORR in patients with RRNHL as defined by the Lugano classification for lymphoma.
6. Part 1 and Part 2: Disease Control Rate (DCR) for RRNHL patients [ Time Frame: Up to 12 months ]
7. Part 1 and Part 2: Progression-free Survival (PFS) for RRMM patients [ Time Frame: From the date of first dose until the date of progressive disease (PD) ]
   Determined by IMWG criteria
8. Part 1 and Part 2: Progression-free Survival (PFS) for RRNHL patients [ Time Frame: From the date of first dose until the date of progressive disease (PD) ]
   Determined by Lugano classification for lymphoma
9. Part 1 and Part 2: Proportion of RRMM participants who achieved MR (minimal response) [ Time Frame: Up to 12 months ]
   MR is defined as the percentage of participants who achieved 25% tumor reduction.
10. Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: Date of the dose administration until death due to any cause (up to 12 months) ]
    Time from the date of the first documentation of response to the date of the first documented PD.
11. Part 1 and Part 2: number of participants with Anti-drug Antibodies following administration of MT-0169 [ Time Frame: Up to 12 months ]
12. Part 2: number of participants with DLTs [ Time Frame: Up to 12 months ]
13. Part 2: number of participants with TEAEs [ Time Frame: Up to 12 months ]
14. Part 1 and Part 2: overall survival (OS) [ Time Frame: From date of the dose administration until death due to any cause (up to 12 months) ]
15. Part 1 and Part 2: Time to Response (TTR) [ Time Frame: From the date of the first dose of the study treatment to the date of the first documentation of response (up to 12 months) ]
16. Part 1 and Part 2: percentage of participants with RRMM who achieved Complete Response (CR) or Very Good Partial Response (VGPR) [ Time Frame: Up to 12 months ]
17. Part 2: measurement of RRNHL tumor CD38 expression level [ Time Frame: Up to 12 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 ≥1 proteasome inhibitor (PI), ≥1 immunomodulatory drug (IMiD), and ≥1 steroid
   2. 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 anti-CD38 therapy is permitted).

4. With measurable disease, defined as ≥1 of the following:

   1. Serum M-protein ≥500 mg/dL (≥5 g/L) on serum protein electrophoresis (SPEP).
   2. Urine M-protein ≥200 mg/24 h on urine protein electrophoresis (UPEP).
   3. Serum FLC assay result with an involved FLC level ≥10 mg/dL (≥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 ≥1 of the following:

   1. Bone marrow (BM) aspirate/biopsy with plasma cell percentage ≥30%
   2. PET imaging with ≥1 plasmacytoma lesion with a single diameter of ≥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 ≤450 millisecond (ms) in males or ≤470 ms in females]

8. Must meet the following clinical laboratory criteria at entry:

   1. Total bilirubin ≤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) ≤2.5*ULN.
   3. Estimated glomerular filtration rate (eGFR) ≥30 (mL/min/1.73 square meter [m2]), using the modification of diet in renal disease (MDRD) equation
   4. 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
   5. 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
   6. Hemoglobin ≥7.5 g/dL without transfusion within 7 days before the lab test.
   7. Serum albumin ≥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 ≤450 ms in males or ≤470 ms in females

3. Must meet the following clinical laboratory criteria at study entry:

   1. Total bilirubin ≤1.5*the ULN, except for Gilbert's syndrome (direct bilirubin must be <2.0*ULN)
   2. Serum ALT and AST ≤2.5*ULN
   3. eGFR ≥30 mL/min/1.73 m2(MDRD equation)
   4. 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
   5. 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
   6. Hemoglobin ≥7.5 g/dL without transfusion within 7 days before the lab test
   7. Serum albumin ≥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 ≥1 PI and ≥1 IMiD
   2. 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)
   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 ≥1 of the following

   1. Serum M-protein ≥50 mg/dL (≥5 g/L) on SPEP.
   2. Urine M-protein ≥200 mg/24 hours on UPEP.
   3. Serum FLC assay result with and involved FLC level ≥10 mg/dL (≥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 ≥30%
   2. PET imaging showing at least 1 plasmacytoma lesion with a single diameter ≥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 ≥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 ≤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 ≥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 ≥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 ≥2)
    3. Non-malignant pleural effusion (Grade ≥2)
    4. Malignant pleural effusion (Grade ≥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 ≥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 ≥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 ≤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 ≥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 ≥2)
    3. Non-malignant pleural effusion (Grade ≥2) OR
    4. Malignant pleural effusion (Grade ≥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 ≥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 ≥2 SIRS/CRS reactions following infusion with any mAbs or CAR T therapy.
17. With a chronic condition requiring systemic corticosteroids ≥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

Contacts and Locations

Contacts

Contact: Sarah Wilson; (862) 283-0440; sarah.wilson@mtem.com

Contact: Jaclyn Keith; jaclyn.keith@mtem.com

Locations

United States, California

University of Southern California; Recruiting

Los Angeles, California, United States, 90033

Contact: Christine Duran 323-865-0371 Duran_C@med.usc.edu

United States, Florida

Mayo Clinic - Jacksonville; Active, not recruiting

Jacksonville, Florida, United States, 32224

Miami University; Recruiting

Miami, Florida, United States, 33136

Contact: Diko Kazandjian 305-243-5001 dkazandjian@miami.edu

United States, Georgia

Northside Hospital; Recruiting

Atlanta, Georgia, United States, 30342

Contact: Scott Solomon, MD 404-255-1930 ssolomon@bmtga.com

United States, Indiana

Indiana University; Recruiting

Indianapolis, Indiana, United States, 46202

Contact: Regina Cohen 317-278-8210 regcohen@iu.edu

United States, Minnesota

Mayo Clinic - Rochester; Active, not recruiting

Rochester, Minnesota, United States, 55905

United States, Ohio

The Ohio State University; Recruiting

Columbus, Ohio, United States, 43201

Contact: Timothy Voorhees, MD 614-293-6974 Timothy.Voorhees@osumc.ed

United States, Pennsylvania

University of Pennsylvania; Not yet recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Sara Whittington 215-662-3575 Sara.Whittington@pennmedicine.upenn.edu

United States, Tennessee

Vanderbilt University Medical Center- Ingram Cancer Center; Recruiting

Nashville, Tennessee, United States, 37203

Contact: Site Contact 615-875-3112 bhagirathbhai.r.dholaria@vumc.org

Principal Investigator: Bhagirathbhai Dholaria

Sponsors and Collaborators

Molecular Templates, Inc.

More Information

• Responsible Party: Molecular Templates, Inc.
• ClinicalTrials.gov Identifier: NCT04017130
• Other Study ID Numbers: MT-0169-001; U1111-1224-6002 ( Other Identifier: WHO ); 2019-000931-24 ( EudraCT Number )
• First Posted: July 12, 2019
• Last Update Posted: September 8, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Molecular Templates, Inc.:

Drug therapy

Additional relevant MeSH terms:

Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders