Blood Cancer, Diffuse Large B Cell Lymphoma, Hematological Malignancy, Leukemia, Lymphocytic, Chronic, B-Cell, Non-Hodgkin's B-cell Lymphoma, Small Lymphocytic Leukemia
Conditions
Keywords
CD20, immunotoxin, NHL, non-Hodgkin's lymphoma, lymphoma, cancer, antibodies, immunotherapy, safety, pharmacokinetics, maximum tolerated dose, MT-3724, relapsed, refractory, leukemia, CLL, SLL, DLBCL, efficacy
Brief summary
The purpose of this study is to evaluate the safety and tolerability of MT-3724 in subjects with relapsed or refractory B-Cell NHL or relapsed and refractory CLL (Part 1 only) and relapsed and refractory DLBCL (Part 2 and Part 3). Part 3 evaluates the efficacy of MT-3724.
Detailed description
This is a three-part Phase 2 study Part 1: (MT-3724 Dose Escalation) Define the maximum tolerated dose (MTD) of MT-3724 \[Completed\] Part 2: (MTD Expansion Cohort) Confirm the safety and tolerability of the MTD of MT-3724 in the MTD Expansion Cohort. Part 3: (Phase 2 MTD Expansion Cohort) Determine the efficacy of MT-3724 as monotherapy in subjects with relapsed or refractory DLBCL based on the overall response rate (ORR) by the revised Lugano Classification for Lymphoma adjusted according to LYRIC. It is anticipated that up to 100 patients will be enrolled in Part 3. Treatment will continue for up to six 21 days cycles. If the subject exhibits SD, CR or PR after the end of Cycle 6 and the investigator determines that the benefit-risk ratio is favorable, then the treatment with MT-3724 may be continued after discussion with the sponsor.
Interventions
DRUGMT-3724 Phase 1
Intravenous dosing Days 1, 3, 5, 8, 10 and 12; MT-3724 infusion over 2 hours on each dosing day over 28 day initial cycle and then 21 week repeat cycles for up to 5 total cycles.
DRUGMT-3724 Phase 2
Intravenous dosing on Days 1, 3, 5, 8, 10 and 12; MT-3724 infusion over 1 hour on each dosing day over 21 day cycle up to 6 cycles and then can be continued for 6 additional cycles.
Sponsors
Molecular Templates, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be informed about the study and fully consent to participation as demonstrated by signing the written ICF before any screening procedure. * Male and female participants \>= 18 years of age at the time of informed consent. * Participants must have relapsed or refractory Diffuse large B cell lymphoma (DLBCL) according to the Revised European American Lymphoma/World Health Organization classification. Participants must have proof of cluster of differentiation 20 plus (CD20+) DLBCL, based on either: * a. historical biopsies (obtained with diagnosis of relapsed or refractory disease), or * b. fresh biopsies * c. bone marrow biopsy, excisional lymph node biopsy, and core biopsy of any involved organ are all acceptable methods; Fine Needle Aspirate is not acceptable. * Participants must have received at least 2 standard of care (SoC) regimens (including anti-CD20 antibody therapy) appropriate for DLBCL treatment. * a. Participants whose prior therapy includes chimeric antigen receptor T-cell (CAR-T-cell) therapy are eligible. * b. Participants who underwent stem cell transplant (SCT) \> 100 days for autologous SCT or \> 180 days for allogeneic SCT before study drug administration. * c. Participants who have been ineligible for SoC DLBCL treatments may be eligible at the investigator's discretion, upon sponsor approval. * Participants must have at least 1 bi-dimensional tumor lesion at screening that is measurable by computerized tomography (CT) and/or magnetic resonance imaging (MRI) according to the Lugano criteria. Bi-dimensionally measurable tumor lesion by CT and/or MRI is defined as longest diameter of \> 1.5 centimeters (cm) for lymph nodes and \> 1.0 cm for extranodal disease. * Participants must have life expectancy of \> 3 months from the start of treatment. * Participants must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Participants must have met ALL the following laboratory criteria: * a. absolute neutrophil count (ANC) \>= 1.0 × 10\^9 cells per liter with no myeloid growth factors (granulocyte colony-stimulating factor \[G-CSF\] or granulocyte-macrophage colony-stimulating factor preparations) administered within 2 weeks of Cycle 1 Day 1. * b. platelet count \>= 50 × 10\^9 cells per liter with no Thrombopoietin-receptor agonists agents or platelet transfusions given within 2 weeks of Cycle 1 Day 1. * c. hemoglobin \>= 8.0 grams per deciliter (g/dL) with no erythropoietin stimulating agents or peripheral red blood cell (PRBC) transfusions within 2 weeks of Cycle 1 Day 1 * d. creatinine clearance (CLcr) to be \>= 50 milliliter per minute (ml/min) either measured or estimated using the Cockcroft-Gault formula. * e. total bilirubin (or direct bilirubin for patients with Gilbert's disease \< 1.5 × upper limit of normal (ULN) * f. alanine transaminase (ALT) ≤ 3.0 × ULN (or \<= 5.0 x ULN if liver involvement). * g. aspartate aminotransferase (AST) \<= 3.0 × ULN (or \<= 5.0 x ULN if liver involvement). * h. international normalized ratio (INR) or prothrombin time (PT) \<= 1.5 x ULN (unless on therapeutic anticoagulants). * i. Activated partial thromboplastin time \<= 1.5 x ULN (unless on therapeutic anticoagulants). * Have adequate serum albumin, as determined by: a. albumin \>= 3.0 g/dL. * QT interval correction for heart rate using Fridericia's formula (QTcF) \<= 480 milliseconds determined as the average of 3 QTcF values from the triplicate electrocardiogram (ECG) obtained at screening. * Women of reproductive potential must have a negative highly sensitive pregnancy test within 72 hours before the start of treatment. Women who are postmenopausal or permanently sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy) may be considered as not of reproductive potential. * Participants of reproductive potential must agree either to abstain continuously from heterosexual intercourse or to use a highly effective birth control method from signing the informed consent until the short term follow-up (STFU) visit for females and until 90 days after the last dose of MT-3724 for males. * Participants must be able to comply with all study-related procedures and medication use.
Exclusion criteria
Prior or Current Therapies * Received any amount of anti-CD20 monoclonal antibodies (mAbs) within the following periods before the start of treatment: * a. Rituximab (Rituxan®/MabThera® or rituximab biosimilar): within 84 days (12 weeks); if a participant has received rituximab within 37 weeks before the start of treatment, then serum rituximab level must be negative (\< 500 nanograms per milliliter \[ng/mL\]) at screening. * b. Obinutuzumab (Gazyva®/Gazyvaro®): 184 days c. Ofatumumab (Arzerra®): 88 days d. Any other anti-CD20 agents (eg, investigational agents), the washout period is 5 half-lives. The investigator must contact the medical monitor to discuss the most Compound: MT-3724 appropriate washout for non-approved CD20-targeting agents, where the half-life (t1/2) is not known. * Received approved or investigational treatment for DLBCL within 4 weeks before the start of treatment. For small molecules (MW \< 0.9 kilodaltons \[kDa\]), the washout is 5 half-lives or at least 2 weeks. Radioimmunoconjugates are excluded within 12 weeks before the start of treatment. * Received radiation therapy to tumor lesions that would serve as target lesions (measurable disease) within 4 weeks before the start of treatment, unless the lesion exhibited objective progression between radiation therapy and screening according to the Lugano Classification o a. Palliative radiation therapy to non-target lesions may be permitted at the investigator's discretion after consultation with the medical monitor and sponsor. * Require the use of systemic immune modulators during study treatment: * a. Systemic immune modulators include, but are not limited to, systemic corticosteroids at doses \> 20 milligrams per day (mg/day) of prednisone equivalent, cyclosporine and tacrolimus. * b. The use of non-steroidal anti-inflammatory drugs (NSAIDS) is permitted. * Received any live vaccines within 4 weeks before the start of treatment. * Prior treatment with MT-3724. Medical History * Current evidence of Common Terminology Criteria for Adverse Events (CTCAE) Grade \> 1 toxicity (due to prior anticancer therapy) before the start of treatment, except for hair loss and those Grade 2 toxicities listed as permitted in other eligibility criteria. * 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. * Known or suspected hypersensitivity to the study drug or excipients contained in the study drug formulation. * Current evidence of hypersensitivity or other underlying illness requiring systemic corticosteroids at doses \> 20 mg/day prednisone equivalent. * Current evidence of uncontrolled human immunodeficiency syndrome (HIV), hepatitis B virus (HBV) or /hepatitis C virus (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: * a. Participants with HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts \>= 350 cells per milliliter may be enrolled, but must be taking appropriate opportunistic infection prophylaxis, if clinically relevant. * b. 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. * c. Participants with positive HCV serology are eligible if quantitative polymerase chain reaction (PCR) for plasma HCV ribonucleic acid (RNA) is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed. * Current evidence of incomplete recovery from surgery or radiotherapy before start of treatment, or planned surgery or radiotherapy from the start of treatment until the end of treatment (EoT) visit, except minor elective surgery deemed acceptable by the investigator or palliative radiation therapy to non-target lesions. * History of cardiovascular, renal, hepatic or any other disease within 3 months before the start of treatment that in the investigator's opinion, 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. * 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. * Current evidence of new or growing brain or spinal metastases during screening. Participants with known brain or spinal metastases may be eligible if they: * a. Had radiotherapy or another appropriate therapy for the brain or spinal metastases; concurrent prophylactic treatment is allowed * b. Neurologic symptoms must be stable and no worse than Grade 2 * c. Have evidence of stable brain or spinal disease on CT or MRI scan obtained within 4 weeks before signing the informed consent and compared with prior imaging results * d. Do not require steroid therapy (or, if applicable, have been stable on dose of no more than prednisone 20 mg/day or equivalent by C1D1) * Women who are pregnant or breastfeeding. * History of non-adherence to the schedule of procedures or medication use. 18. Current evidence of Graft vs Host Disease * History or current evidence of significant cardiovascular disease including, but not limited to, the following conditions: * a. Unstable angina (symptoms of angina at rest) or new-onset angina within 3 months before the start of treatment. * b. Arterial thrombosis or pulmonary embolism within 3 months before the start of treatment. * c. Myocardial infarction or stroke within 3 months before the start of treatment. * d. Pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade \>= 2), non-malignant pleural effusion (CTCAE Grade ≥ 2) or malignant pleural effusion (CTCAE Grade \>= 3) within 3 months before the start of treatment with MT-3724. * e. Congestive heart failure (New York Heart Association \[NYHA\] Class III or IV) at screening or left ventricular ejection fraction (LVEF) \<= 45 percent (%), assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 1 month before starting study treatment (inclusion of participants with LVEF between 40% to 45% should be discussed with the medical monitor and approved by the sponsor). (ECHO or MUGA 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 potentially cardiotoxic agents since then). * f. 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 and sponsor 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724 | Part 1 and 2: Days 1, 3 and 12 | Blood samples were collected at indicated timepoints for the determination of tmax. |
| Part 1 and 2: Half Life (t1/2) of MT-3724 | Part 1 and 2: Days 1, 3 and 12 | Blood samples were collected at indicated timepoints for the analysis of t1/2 of MT-3724. |
| Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | Part 1 and 2: Days 1, 3 and 12 | Blood samples were collected at indicated timepoints for the determination of AUC (0-4), AUC (0-infinity) and AUClast. |
| Part 1: Number of Participants With Dose Limiting Toxicities of a Single Cycle of MT-3724 | Days 1, 3, 5, 8, 10 and 12 | The MTD is defined to be the dose cohort below which participants experience dose-limiting toxicities during cycle 1. Dose-limiting toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 |
| Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274 | Part 1 and 2 : Days 1, 3 and 12 | Blood samples were collected at indicated timepoints for the determination of Cmax of MT-3274. |
| Part 1 and 2: Volume of Distribution (Vz) of MT-3724 | Part 1 and 2: Days 1, 3 and 12 | Blood samples were collected at indicated timepoints for the analysis of Vz of MT-3724. |
| Part 1 and 2: Clearance (CL) of MT-3724 | Part 1 and 2: Days 1, 3 and 12 | Blood samples were collected at indicated timepoints for the analysis of CL of MT-3724. |
| Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Part 1 and 2: Cycle 1: Days 8 and 23; Cycle 3: Day1; Cycle 5: Day 1 and Day 120 (end of study) | CD19+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus |
| Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Part 1 and 2: Cycle 1, Day 23; Cycle 2, Day 1; Cycle 3, Day 1; Cycle 4, Day 1; Cycle 5, Day 1 and Day 120 (end of study) | Blood samples were collected to analyze the presence of ADA that bind MT-3724. Number of participants with positive ADA confirmed has been presented. |
| Part 3: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs | Up to Day 45 | An adverse event is any untoward medical occurrence or clinical investigation in a participant administered a pharmaceutical product(s) and which does not necessarily have to have a causal relationship with this experimental treatment(s). SAE is any untoward medical occurrence, at any dose; is fatal or life-threatening, is life-threatening, results in permanently disabling; results in unplanned in-patient hospitalization or prolongation of existing hospitalization; results in a congenital abnormality or birth defect; important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention. |
| Part 3: Number of Participants With Clinically Significant Laboratory Parameters | Up to Day 45 | Blood samples were collected at indicated timepoints for the analysis of laboratory parameters. |
| Part 3: Number of Participants With Clinically Significant Electrocardiogram (ECG) Values | Up to Day 26 | Standard resting 12-lead ECG assessments was performed after the participant has rested quietly for at least 5 minutes in supine or semi-recumbent position. |
| Part 3: Number Participants With Clinically Significant Vital Signs | Up to Day 45 | Vital signs including systolic and diastolic blood pressure, respiratory rate, heart rate and body temperature were assessed at indicated time points. |
| Part 3: Number of Participants With Clinically Significant Physical Findings | Up to Day 26 | Physical examination was performed by a physician or a qualified delegate at the investigating site. |
| Part 4: Overall Response Rate (ORR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Overall response rate is defined as the percentage of participants with either a CR or a PR as determined by independent, blinded central review. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 4: DOR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Duration of response was defined as the time from the first occurrence of either complete or partial response to first documented evidence of disease recurrence or progression. Participants without evidence of progression were planned to be censored at time of last disease assessment. Only responders (CR or PR) were planned to be included for this analysis. |
| Part 4: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs | Up to Day 45 | An adverse event is any untoward medical occurrence or clinical investigation in a participant administered a pharmaceutical product(s) and which does not necessarily have to have a causal relationship with this experimental treatment(s). SAE is any untoward medical occurrence, at any dose; is fatal or life-threatening, is life-threatening, results in permanently disabling; results in unplanned in-patient hospitalization or prolongation of existing hospitalization; results in a congenital abnormality or birth defect; important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention. |
| Part 4: Number of Participants With SAEs | Up to Day 45 | A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement or is associated with liver injury and impaired liver function. |
| Part 4: Number of Participants With Clinically Significant Laboratory Parameters | Up to Day 45 | Blood samples were planned to be collected for the analysis of laboratory parameters. |
| Part 4: Number Participants With Clinically Significant Vital Signs | Up to Day 45 | Vital signs parameters including systolic and diastolic blood pressure, heart rate, respiration rate, body temperature and body weight were planned to be analyzed. |
| Part 4: Number of Participants With Clinically Significant ECG Values | Up to Day 26 | Standard resting 12-lead ECG assessments was planned to be performed after the participant has rested quietly for at least 5 minutes in supine or semi-recumbent position. |
| Part 4: Number of Participants With Adverse Events Suggestive of Cardiotoxicity | Up to Day 26 | Number of participants with any adverse events leading to cardiotoxicity when treated with MT-3724 was planned to be analyzed. |
| Part 4: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Overall response rate was defined as the percentage of participants with either a CR or a PR as determined by investigator assessment. |
| Part 4: DCR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL | Up to Day 45 | DCR was defined as percentage of participants who has achieved CR, PR and stable disease. |
| Part 4: Progression-free Survival (PFS) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Progression-free survival was defined as the time from study enrollment to the earliest date of disease progression or death from any cause. |
| Part 4: Overall Survival (OS) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Overall survival was defined as the time from study enrollment to death from any cause. |
| Part 4: Cmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of Cmax of MT-3724 monotherapy. |
| Part 4: Tmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of Tmax of MT-3724 monotherapy. |
| Part 4: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 monotherapy. |
| Part 4: t1/2 of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of t1/2 of MT-3724 monotherapy. |
| Part 4: Vz of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of Vz of MT-3724 monotherapy. |
| Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Up to Day 45 | An adverse event is any untoward medical occurrence or clinical investigation in a participant administered a pharmaceutical product(s) and which does not necessarily have to have a causal relationship with this experimental treatment(s). SAE is any untoward medical occurrence, at any dose; is fatal or life-threatening, is life-threatening, results in permanently disabling; results in unplanned in-patient hospitalization or prolongation of existing hospitalization; results in a congenital abnormality or birth defect; important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention. |
| Part 4: PD of MT-3724 Measured by B-cell Count in Participants With Relapsed or Refractory DCBCL | Up to Day 45 | Pharmacodynamics of MT-3724 was planned to be measured by B-cell count in participants with relapsed of refractory DCBCL using flow cytometry. |
| Part 4: PD of MT-3724 Measured by Immunophenotyping in Participants With Relapsed or Refractory DCBCL | Up to Day 45 | Pharmacodynamics of MT-3724 was planned to be measured by immunophenotyping in participants with relapsed of refractory DCBCL using flow cytometry. |
| Part 4: PD of MT-3724 Measured by Circulating Immunoglobulins in Participants With Relapsed or Refractory DCBCL | Up to Day 45 | Pharmacodynamics of MT-3724 was planned to be measured by circulating immunoglobulins in participants with relapsed of refractory DCBCL. |
| Part 4: Number of Participants With ADA When Treated With MT-3724 | Up to Day 45 | Blood samples were planned to be collected to analyze the presence of ADA that bind MT-3724. |
| Part 4: CL of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of CL of MT-3724 monotherapy. |
| Part 3: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL by the Lugano Classification for Lymphoma | Up to Day 45 | Overall response rate is defined as the percentage of participants with either a complete response (CR) or a partial response (PR) as determined by independent, blinded central review board. |
| Part 3: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Overall response rate is defined as the percentage of participants with either a CR or a PR as determined by investigator assessment. |
| Part 3: Duration of Tumor Response (DOR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL | Up to Day 45 | DOR defined as time from initial documentation of tumor response (CR or PR) to disease progression. |
| Part 3: Disease Control Rate (DCR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL | Up to Day 45 | DCR defined as percentage of participants who have achieved CR, PR and stable disease. |
| Part 3: Cmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of Cmax of MT-3724 monotherapy. |
| Part 3: Tmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of tmax of MT-3724 monotherapy. |
| Part 3: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 monotherapy. |
| Part 3: t1/2 of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of t1/2 of MT-3724 monotherapy. |
| Part 3: Vz of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of Vz of MT-3724 monotherapy. |
| Part 3: CL of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | Up to Day 45 | Blood samples were planned to be collected at indicated timepoints for the analysis of CL of MT-3724 monotherapy |
| Part 3: PD of MT-3724 Measured by B-cell Count in Participants With Relapsed or Refractory DCBCL | Up to Day 45 | Pharmacodynamics of MT-3724 was planned to be measured by B-cell count in participants with relapsed of refractory DCBCL using flow cytometry. |
| Part 3: PD of MT-3724 Measured by Immunophenotyping in Participants With Relapsed or Refractory DCBCL | Up to Day 45 | Pharmacodynamics of MT-3724 was planned to be measured by immunophenotyping in participants with relapsed of refractory DCBCL using flow cytometry. |
| Part 3: PD of MT-3724 Measured by Circulating Immunoglobulins in Participants With Relapsed or Refractory DCBCL | Up to Day 45 | Pharmacodynamics of MT-3724 was planned to be measured by circulating immunoglobulins in participants with relapsed of refractory DCBCL. |
| Part 3: Number of Participants With ADA When Treated With MT-3724 | Up to Day 45 | Blood samples were planned to be collected to analyze the presence of ADA that bind MT-3724. |
Countries
Belarus, Canada, Georgia, Israel, Moldova, Poland, Serbia, Spain, Ukraine, United States
Participant flow
Recruitment details
This 4-part study evaluated safety, pharmacodynamics and efficacy of MT-3724 in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Part 1 was multiple ascending dose study and Parts 2, 3 and 4 were multi-center, multinational, open-label, single-arm evaluation of MT-3724 administered as monotherapy in repeat doses.
Pre-assignment details
A total of 27 participants were enrolled in Parts 1 and 2 and 11 participants in Part 3. Part 2 was analyzed as a single arm as data was not collected for each dose level separately. The study was terminated as no participants in Part 3 showed a response and the potential risks outweighed potential benefit.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) Participants in this cohort received 5 mcg/kg/dose/day on Days 1, 3, 5, 8, 10, and 12 for the first cycle of experimental drug followed by 9 days observation (Days 13 - 21) for a maximum of 6 cycles. | 3 |
| Part 1: Cohort 2- 10 mcg/kg/Dose Participants in this cohort received 10 mcg/kg/dose/day on Days 1, 3, 5, 8, 10, and 12 for the first cycle of experimental drug followed by 9 days observation (Days 13 - 21) for a maximum of 6 cycles. | 3 |
| Part 1: Cohort 3- 20 mcg/kg/Dose Participants in this cohort received 20 mcg/kg/dose/day on Days 1, 3, 5, 8, 10, and 12 for the first cycle of experimental drug followed by 9 days observation (Days 13 - 21) for a maximum of 6 cycles. | 3 |
| Part 1: Cohort 4- 50 mcg/kg/Dose Participants in this cohort received 50 mcg/kg/dose/day on Days 1, 3, 5, 8, 10, and 12 for the first cycle of experimental drug followed by 9 days observation (Days 13 - 21) for a maximum of 6 cycles. | 4 |
| Part 1: Cohort 5- 100 mcg/kg/Dose Participants in this cohort received 100 mcg/kg/dose/day on Days 1, 3, 5, 8, 10, and 12 for the first cycle of experimental drug followed by 9 days observation (Days 13 - 21) for a maximum of 6 cycles. | 2 |
| Part 1: Cohort 6- 75 mcg/kg/Dose Participants in this cohort received 75 mcg/kg/dose/day on Days 1, 3, 5, 8, 10, and 12 of 21-Day cycle for up to 4 additional cycles to explore safety, tolerability and tumor response to repeat doses of MT-3724. | 6 |
| Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) Participants in this cohort received 50 or 75 mcg/kg/dose/day on Days 1, 3, 5, 8, 10, and 12 days of 21-Day cycle up to 4 additional cycles to explore safety, tolerability and tumor response to repeat doses of MT-3724. | 6 |
| Part 3: All MT-3724 Treated Participants MT-3724 was administered at a dose of 50µg/kg/dose via IV infusion for all participants | 11 |
| Part 4: All MT-3724 Treated Participants Participants in this arm were planned to receive all doses of MT-3724 as IV infusion over 1 hour in a 21-day cycle | 0 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 and 2 ( Up to Day 112) | Adverse Event | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Part 1 and 2 ( Up to Day 112) | Death | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 3 (Up to Day 112) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 3 (Up to Day 112) | Clinical disease progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Part 3 (Up to Day 112) | Disease progression (radiographic per lugano) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 0 |
| Part 3 (Up to Day 112) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1: Cohort 6- 75 mcg/kg/Dose | Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) | Part 3: All MT-3724 Treated Participants | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 73.3 Years STANDARD_DEVIATION 6.43 | 70.7 Years STANDARD_DEVIATION 8.74 | 64.3 Years STANDARD_DEVIATION 14.01 | 57.8 Years STANDARD_DEVIATION 16.66 | 65.0 Years STANDARD_DEVIATION 4.24 | 67.2 Years STANDARD_DEVIATION 4.4 | 59.3 Years STANDARD_DEVIATION 10.58 | 57.5 Years STANDARD_DEVIATION 14.77 | 64.4 Years STANDARD_DEVIATION 5.9 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 5 Participants | 6 Participants | 11 Participants | 34 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 4 Participants | 5 Participants | 3 Participants | 20 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 8 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 1 / 4 | 0 / 2 | 0 / 6 | 0 / 6 | 1 / 11 | 0 / 0 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 2 / 2 | 6 / 6 | 6 / 6 | 11 / 11 | 0 / 0 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 2 / 3 | 4 / 4 | 2 / 2 | 3 / 6 | 2 / 6 | 3 / 11 | 0 / 0 |
Outcome results
Primary
Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes
CD19+ cells in the peripheral blood were counted as measures of malignant B-cells and were measured by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus
Time frame: Part 1 and 2: Cycle 1: Days 8 and 23; Cycle 3: Day1; Cycle 5: Day 1 and Day 120 (end of study)
Population: Pharmacokinetic Analysis Set. Part 2 was analyzed as a single arm as data was not collected for each dose level separately.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 1 Day 23 | 143 10^3 cells per microliter | — |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Day 120 (End of study) | 79.0 10^3 cells per microliter | — |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 3 Day 1 | 67.0 10^3 cells per microliter | — |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 5 Day 1 | 132 10^3 cells per microliter | — |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 1 Day 8 | 114 10^3 cells per microliter | — |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 5 Day 1 | 180 10^3 cells per microliter | — |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 1 Day 8 | 325 10^3 cells per microliter | — |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 1 Day 23 | 104 10^3 cells per microliter | — |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Day 120 (End of study) | 184 10^3 cells per microliter | — |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 3 Day 1 | 134 10^3 cells per microliter | — |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 5 Day 1 | 53.0 10^3 cells per microliter | — |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 3 Day 1 | 60.0 10^3 cells per microliter | — |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Day 120 (End of study) | 49.0 10^3 cells per microliter | — |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 1 Day 8 | 244 10^3 cells per microliter | — |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 1 Day 23 | 131 10^3 cells per microliter | — |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 3 Day 1 | 1170 10^3 cells per microliter | Standard Deviation 1965.6 |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 1 Day 8 | 57.7 10^3 cells per microliter | Standard Deviation 91.166 |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 5 Day 1 | 26.0 10^3 cells per microliter | Standard Deviation 31.1127 |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Day 120 (End of study) | 22.87 10^3 cells per microliter | Standard Deviation 18.17 |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 3 Day 1 | 34.0 10^3 cells per microliter | — |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 1 Day 23 | 67.0 10^3 cells per microliter | — |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 1 Day 8 | 126 10^3 cells per microliter | — |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Day 120 (End of study) | 44.0 10^3 cells per microliter | — |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Absolute Values of Cluster of Differentiation 19 Plus (CD19+) for B-cell Lymphocytes | Cycle 5 Day 1 | 39.0 10^3 cells per microliter | — |
Primary
Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724
Blood samples were collected at indicated timepoints for the determination of AUC (0-4), AUC (0-infinity) and AUClast.
Time frame: Part 1 and 2: Days 1, 3 and 12
Population: Pharmacokinetic Analysis Set. Part 2 was analyzed as a single arm as data was not collected for each dose level separately.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUClast | NA h*ng/ml |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-infinity) | NA h*ng/ml |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-4) | NA h*ng/ml |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-infinity) | NA h*ng/ml |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-4) | NA h*ng/ml |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUClast | NA h*ng/ml |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUClast | NA h*ng/ml |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-4) | NA h*ng/ml |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-infinity) | NA h*ng/ml |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-infinity) | NA h*ng/ml |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-4) | NA h*ng/ml |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUClast | NA h*ng/ml |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-infinity) | NA h*ng/ml |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-4) | NA h*ng/ml |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUClast | NA h*ng/ml |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-4) | NA h*ng/ml |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUClast | NA h*ng/ml |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-infinity) | NA h*ng/ml |
| Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUClast | NA h*ng/ml |
| Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-infinity) | NA h*ng/ml |
| Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) | Part 1 and 2: Area Under the Plasma Concentration Time Curve From 0 to 4 Hours (AUC [0-4]), AUC (0-infinity) and AUC From Dosing to Last Measurable Concentration (AUClast) of MT-3724 | AUC (0-4) | NA h*ng/ml |
Primary
Part 1 and 2: Clearance (CL) of MT-3724
Blood samples were collected at indicated timepoints for the analysis of CL of MT-3724.
Time frame: Part 1 and 2: Days 1, 3 and 12
Population: Pharmacokinetic Analysis Set. Part 2 was analyzed as a single arm as data was not collected for each dose level separately.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Clearance (CL) of MT-3724 | NA Liters per hour |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Clearance (CL) of MT-3724 | NA Liters per hour |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Clearance (CL) of MT-3724 | NA Liters per hour |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Clearance (CL) of MT-3724 | NA Liters per hour |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Clearance (CL) of MT-3724 | NA Liters per hour |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Clearance (CL) of MT-3724 | NA Liters per hour |
| Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) | Part 1 and 2: Clearance (CL) of MT-3724 | NA Liters per hour |
Primary
Part 1 and 2: Half Life (t1/2) of MT-3724
Blood samples were collected at indicated timepoints for the analysis of t1/2 of MT-3724.
Time frame: Part 1 and 2: Days 1, 3 and 12
Population: Pharmacokinetic Analysis Set. Part 2 was analyzed as a single-arm as data was not collected for each dose level separately.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Half Life (t1/2) of MT-3724 | NA Hour |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Half Life (t1/2) of MT-3724 | NA Hour |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Half Life (t1/2) of MT-3724 | NA Hour |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Half Life (t1/2) of MT-3724 | NA Hour |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Half Life (t1/2) of MT-3724 | NA Hour |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Half Life (t1/2) of MT-3724 | NA Hour |
| Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) | Part 1 and 2: Half Life (t1/2) of MT-3724 | NA Hour |
Primary
Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274
Blood samples were collected at indicated timepoints for the determination of Cmax of MT-3274.
Time frame: Part 1 and 2 : Days 1, 3 and 12
Population: Pharmacokinetic Analysis Set (PAS). All subjects from the Safety Set with sufficient serum concentration data to determine the primary PK parameters. Only those participants with data available at specified timepoints were analyzed. Part 2 was analyzed as a single arm as data was not collected for each dose level separately.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274 | NA Nanograms per milliliter |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274 | NA Nanograms per milliliter |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274 | NA Nanograms per milliliter |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274 | NA Nanograms per milliliter |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274 | NA Nanograms per milliliter |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274 | NA Nanograms per milliliter |
| Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) | Part 1 and 2: Maximum Observed Concentrations (Cmax) of MT-3274 | NA Nanograms per milliliter |
Primary
Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed
Blood samples were collected to analyze the presence of ADA that bind MT-3724. Number of participants with positive ADA confirmed has been presented.
Time frame: Part 1 and 2: Cycle 1, Day 23; Cycle 2, Day 1; Cycle 3, Day 1; Cycle 4, Day 1; Cycle 5, Day 1 and Day 120 (end of study)
Population: Pharmacokinetic Analysis Set. Only those participants with data available at specified time points has been presented. Part 2 was analyzed as a single arm as data was not collected for each dose level separately.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 1 Day 23 | 0 Participants |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 2 Day 1 | 0 Participants |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 3 Day 1 | 0 Participants |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 4 Day 1 | 1 Participants |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 5 Day 1 | 1 Participants |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Day 120 (end of study) | 2 Participants |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 2 Day 1 | 3 Participants |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 4 Day 1 | 2 Participants |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Day 120 (end of study) | 2 Participants |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 1 Day 23 | 3 Participants |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 3 Day 1 | 2 Participants |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 5 Day 1 | 2 Participants |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Day 120 (end of study) | 1 Participants |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 5 Day 1 | 1 Participants |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 4 Day 1 | 1 Participants |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 3 Day 1 | 1 Participants |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 1 Day 23 | 1 Participants |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 2 Day 1 | 1 Participants |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 4 Day 1 | 2 Participants |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 2 Day 1 | 4 Participants |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 3 Day 1 | 2 Participants |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Day 120 (end of study) | 4 Participants |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 5 Day 1 | 1 Participants |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 1 Day 23 | 1 Participants |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 1 Day 23 | 0 Participants |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 5 Day 1 | 0 Participants |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 2 Day 1 | 0 Participants |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 3 Day 1 | 0 Participants |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 4 Day 1 | 0 Participants |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Day 120 (end of study) | 0 Participants |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 4 Day 1 | 1 Participants |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 3 Day 1 | 1 Participants |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 5 Day 1 | 1 Participants |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Day 120 (end of study) | 3 Participants |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 2 Day 1 | 2 Participants |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Number of Participants With Positive Anti-drug Antibody (ADA) Confirmed | Cycle 1 Day 23 | 1 Participants |
Primary
Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724
Blood samples were collected at indicated timepoints for the determination of tmax.
Time frame: Part 1 and 2: Days 1, 3 and 12
Population: Pharmacokinetic Analysis Set. Part 2 was analyzed as a single arm as data was not collected for each dose level separately.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724 | NA Hours |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724 | NA Hours |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724 | NA Hours |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724 | NA Hours |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724 | NA Hours |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724 | NA Hours |
| Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) | Part 1 and 2: Time to Achieve Cmax (Tmax) of MT-3724 | NA Hours |
Primary
Part 1 and 2: Volume of Distribution (Vz) of MT-3724
Blood samples were collected at indicated timepoints for the analysis of Vz of MT-3724.
Time frame: Part 1 and 2: Days 1, 3 and 12
Population: Pharmacokinetic Analysis Set. Part 2 was analyzed as a single arm as data was not collected for each dose level separately.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Volume of Distribution (Vz) of MT-3724 | NA Liters |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Volume of Distribution (Vz) of MT-3724 | NA Liters |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Volume of Distribution (Vz) of MT-3724 | NA Liters |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Volume of Distribution (Vz) of MT-3724 | NA Liters |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Volume of Distribution (Vz) of MT-3724 | NA Liters |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Volume of Distribution (Vz) of MT-3724 | NA Liters |
| Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) | Part 1 and 2: Volume of Distribution (Vz) of MT-3724 | NA Liters |
Primary
Part 1: Number of Participants With Dose Limiting Toxicities of a Single Cycle of MT-3724
The MTD is defined to be the dose cohort below which participants experience dose-limiting toxicities during cycle 1. Dose-limiting toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time frame: Days 1, 3, 5, 8, 10 and 12
Population: Safety Set comprises of all participants who received any amount of MT-3724
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1: Number of Participants With Dose Limiting Toxicities of a Single Cycle of MT-3724 | 0 Participants |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1: Number of Participants With Dose Limiting Toxicities of a Single Cycle of MT-3724 | 0 Participants |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1: Number of Participants With Dose Limiting Toxicities of a Single Cycle of MT-3724 | 0 Participants |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1: Number of Participants With Dose Limiting Toxicities of a Single Cycle of MT-3724 | 0 Participants |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1: Number of Participants With Dose Limiting Toxicities of a Single Cycle of MT-3724 | 2 Participants |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1: Number of Participants With Dose Limiting Toxicities of a Single Cycle of MT-3724 | 0 Participants |
Primary
Part 3: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs
An adverse event is any untoward medical occurrence or clinical investigation in a participant administered a pharmaceutical product(s) and which does not necessarily have to have a causal relationship with this experimental treatment(s). SAE is any untoward medical occurrence, at any dose; is fatal or life-threatening, is life-threatening, results in permanently disabling; results in unplanned in-patient hospitalization or prolongation of existing hospitalization; results in a congenital abnormality or birth defect; important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention.
Time frame: Up to Day 45
Population: Safety Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 3: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs | Serious TEAEs | 3 Participants |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 3: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs | Non-serious TEAEs | 11 Participants |
Primary
Part 3: Number of Participants With Clinically Significant Electrocardiogram (ECG) Values
Standard resting 12-lead ECG assessments was performed after the participant has rested quietly for at least 5 minutes in supine or semi-recumbent position.
Time frame: Up to Day 26
Population: Safety Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 3: Number of Participants With Clinically Significant Electrocardiogram (ECG) Values | 0 Participants |
Primary
Part 3: Number of Participants With Clinically Significant Laboratory Parameters
Blood samples were collected at indicated timepoints for the analysis of laboratory parameters.
Time frame: Up to Day 45
Population: Safety Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 3: Number of Participants With Clinically Significant Laboratory Parameters | 0 Participants |
Primary
Part 3: Number of Participants With Clinically Significant Physical Findings
Physical examination was performed by a physician or a qualified delegate at the investigating site.
Time frame: Up to Day 26
Population: Safety Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 3: Number of Participants With Clinically Significant Physical Findings | 2 Participants |
Primary
Part 3: Number Participants With Clinically Significant Vital Signs
Vital signs including systolic and diastolic blood pressure, respiratory rate, heart rate and body temperature were assessed at indicated time points.
Time frame: Up to Day 45
Population: Safety Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 3: Number Participants With Clinically Significant Vital Signs | 0 Participants |
Primary
Part 4: Overall Response Rate (ORR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Overall response rate is defined as the percentage of participants with either a CR or a PR as determined by independent, blinded central review.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs
An adverse event is any untoward medical occurrence or clinical investigation in a participant administered a pharmaceutical product(s) and which does not necessarily have to have a causal relationship with this experimental treatment(s). SAE is any untoward medical occurrence, at any dose; is fatal or life-threatening, is life-threatening, results in permanently disabling; results in unplanned in-patient hospitalization or prolongation of existing hospitalization; results in a congenital abnormality or birth defect; important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention.
Time frame: Up to Day 45
Population: Safety Set comprises of all participants who received any amount of MT-3724. Part 2 was analyzed as a single arm as data was not collected for each dose level separately.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Serious TEAEs | 1 Participants |
| Part 1: Cohort 1 - 5 Micrograms/Kilogram/Dose (mcg/kg/Dose) | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Non-serious TEAEs | 3 Participants |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Serious TEAEs | 0 Participants |
| Part 1: Cohort 2- 10 mcg/kg/Dose | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Non-serious TEAEs | 3 Participants |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Serious TEAEs | 2 Participants |
| Part 1: Cohort 3- 20 mcg/kg/Dose | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Non-serious TEAEs | 3 Participants |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Serious TEAEs | 4 Participants |
| Part 1: Cohort 4- 50 mcg/kg/Dose | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Non-serious TEAEs | 4 Participants |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Serious TEAEs | 2 Participants |
| Part 1: Cohort 5- 100 mcg/kg/Dose | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Non-serious TEAEs | 2 Participants |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Serious TEAEs | 3 Participants |
| Part 1: Cohort 6- 75 mcg/kg/Dose | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Non-serious TEAEs | 6 Participants |
| Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Serious TEAEs | 2 Participants |
| Part 2: Cohort 7- MTD Expansion Cohort (50 or 75 mcg/kg/Dose) | Part 1 and 2: Number of Participants Reporting Worst Case Serious Treatment Emergent Adverse Events (TEAEs) and Non-serious TEAEs | Non-serious TEAEs | 6 Participants |
Secondary
Part 3: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 monotherapy.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Part 3: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | AUC (0-4) | — |
| Unknown | Part 3: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | AUC (0-infinity) | — |
| Unknown | Part 3: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | AUClast | — |
Secondary
Part 3: CL of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of CL of MT-3724 monotherapy
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 3: Cmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of Cmax of MT-3724 monotherapy.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 3: Disease Control Rate (DCR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
DCR defined as percentage of participants who have achieved CR, PR and stable disease.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 3: Duration of Tumor Response (DOR) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
DOR defined as time from initial documentation of tumor response (CR or PR) to disease progression.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 3: Number of Participants With ADA When Treated With MT-3724
Blood samples were planned to be collected to analyze the presence of ADA that bind MT-3724.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 3: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Overall response rate is defined as the percentage of participants with either a CR or a PR as determined by investigator assessment.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 3: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL by the Lugano Classification for Lymphoma
Overall response rate is defined as the percentage of participants with either a complete response (CR) or a partial response (PR) as determined by independent, blinded central review board.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination.
Secondary
Part 3: PD of MT-3724 Measured by B-cell Count in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by B-cell count in participants with relapsed of refractory DCBCL using flow cytometry.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 3: PD of MT-3724 Measured by Circulating Immunoglobulins in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by circulating immunoglobulins in participants with relapsed of refractory DCBCL.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 3: PD of MT-3724 Measured by Immunophenotyping in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by immunophenotyping in participants with relapsed of refractory DCBCL using flow cytometry.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 3: t1/2 of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of t1/2 of MT-3724 monotherapy.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 3: Tmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of tmax of MT-3724 monotherapy.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 3: Vz of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of Vz of MT-3724 monotherapy.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 monotherapy.
Time frame: Up to Day 45
Population: Pharmacokinetic Analysis Set. The data was not collected due to early study termination
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Part 4: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | AUC (0-infinity) | — |
| Unknown | Part 4: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | AUC (0-4) | — |
| Unknown | Part 4: AUC (0-4), AUC (0-infinity) and AUClast of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL | AUClast | — |
Secondary
Part 4: CL of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of CL of MT-3724 monotherapy.
Time frame: Up to Day 45
Population: Pharmacokinetic Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: Cmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of Cmax of MT-3724 monotherapy.
Time frame: Up to Day 45
Population: Pharmacokinetic Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: DCR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
DCR was defined as percentage of participants who has achieved CR, PR and stable disease.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: DOR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Duration of response was defined as the time from the first occurrence of either complete or partial response to first documented evidence of disease recurrence or progression. Participants without evidence of progression were planned to be censored at time of last disease assessment. Only responders (CR or PR) were planned to be included for this analysis.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs
An adverse event is any untoward medical occurrence or clinical investigation in a participant administered a pharmaceutical product(s) and which does not necessarily have to have a causal relationship with this experimental treatment(s). SAE is any untoward medical occurrence, at any dose; is fatal or life-threatening, is life-threatening, results in permanently disabling; results in unplanned in-patient hospitalization or prolongation of existing hospitalization; results in a congenital abnormality or birth defect; important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention.
Time frame: Up to Day 45
Population: Safety Set. The data was not collected due to early study termination
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Part 4: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs | TEAEs | — |
| Unknown | Part 4: Number of Participants Reporting Serious Treatment-emergent Adverse Events (TEAEs) and Non-serious TEAEs | Severe TEAEs | — |
Secondary
Part 4: Number of Participants With ADA When Treated With MT-3724
Blood samples were planned to be collected to analyze the presence of ADA that bind MT-3724.
Time frame: Up to Day 45
Population: Pharmacokinetic Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: Number of Participants With Adverse Events Suggestive of Cardiotoxicity
Number of participants with any adverse events leading to cardiotoxicity when treated with MT-3724 was planned to be analyzed.
Time frame: Up to Day 26
Population: Safety Set. The data was not collected due to early study termination
Secondary
Part 4: Number of Participants With Clinically Significant ECG Values
Standard resting 12-lead ECG assessments was planned to be performed after the participant has rested quietly for at least 5 minutes in supine or semi-recumbent position.
Time frame: Up to Day 26
Population: Safety Set. The data was not collected due to early study termination
Secondary
Part 4: Number of Participants With Clinically Significant Laboratory Parameters
Blood samples were planned to be collected for the analysis of laboratory parameters.
Time frame: Up to Day 45
Population: Safety Set. The data was not collected due to early study termination
Secondary
Part 4: Number of Participants With SAEs
A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement or is associated with liver injury and impaired liver function.
Time frame: Up to Day 45
Population: Safety Set. The data was not collected due to early study termination
Secondary
Part 4: Number Participants With Clinically Significant Vital Signs
Vital signs parameters including systolic and diastolic blood pressure, heart rate, respiration rate, body temperature and body weight were planned to be analyzed.
Time frame: Up to Day 45
Population: Safety Set. The data was not collected due to early study termination
Secondary
Part 4: ORR in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Overall response rate was defined as the percentage of participants with either a CR or a PR as determined by investigator assessment.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: Overall Survival (OS) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Overall survival was defined as the time from study enrollment to death from any cause.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: PD of MT-3724 Measured by B-cell Count in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by B-cell count in participants with relapsed of refractory DCBCL using flow cytometry.
Time frame: Up to Day 45
Population: Pharmacokinetic Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: PD of MT-3724 Measured by Circulating Immunoglobulins in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by circulating immunoglobulins in participants with relapsed of refractory DCBCL.
Time frame: Up to Day 45
Population: Pharmacokinetic Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: PD of MT-3724 Measured by Immunophenotyping in Participants With Relapsed or Refractory DCBCL
Pharmacodynamics of MT-3724 was planned to be measured by immunophenotyping in participants with relapsed of refractory DCBCL using flow cytometry.
Time frame: Up to Day 45
Population: Pharmacokinetic Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: Progression-free Survival (PFS) in MT-3724 Treated Participants With Relapsed or Refractory DLBCL
Progression-free survival was defined as the time from study enrollment to the earliest date of disease progression or death from any cause.
Time frame: Up to Day 45
Population: Full Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: t1/2 of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of t1/2 of MT-3724 monotherapy.
Time frame: Up to Day 45
Population: Pharmacokinetic Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: Tmax of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of Tmax of MT-3724 monotherapy.
Time frame: Up to Day 45
Population: Pharmacokinetic Analysis Set. The data was not collected due to early study termination
Secondary
Part 4: Vz of MT-3724 Monotherapy in Participants With Relapsed or Refractory DLBCL
Blood samples were planned to be collected at indicated timepoints for the analysis of Vz of MT-3724 monotherapy.
Time frame: Up to Day 45
Population: Pharmacokinetic Analysis Set. The data was not collected due to early study termination