A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The main aims of this 3-part study are as follows: Part 1: To determine any side effects from modakafusp alfa single treatment and how often they occur. The dose of modakafusp alfa will be increased a little at a time until the highest dose that does not cause harmful side effects is found. Part 2: To assess clinical activity of one or more dosing schedules of modakafusp alfa alone in participants with relapsed/refractory multiple myeloma. Dexamethasone standard dose will be administered with one or more selected dose of modakafusp alfa in selected group of participants. Part 3: To find the optimal dose with the more favorable risk-benefit profile of modakafusp alfa. Participants will receive modakafusp alfa at one of two doses which will be given through a vein.

Detailed Description
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The drug being tested in this study, and which will be given through a vein, is called modakafusp alfa (TAK-573 ) as single agent or in combination with dexamethasone. The study will determine the safety, tolerability, and efficacy of modakafusp alfa as single agent and in combination with dexamethasone in participants with relapsed/refractory multiple myeloma (RRMM). The study consists of 3 Parts: Part 1: Dose Escalation, Part 2: Dose Expansion, Part 3: Dose Extension The study will enroll approximately 65 participants in Part 1, 35 in Part 2, and 236 in Part 3. Participants will be assigned to one of the following treatment groups in Parts 1 and 2 of the study. Participants will be randomly assigned in Part 3 of the study as given below: Part 1 (Dose Escalation) Schedule A: Modakafusp alfa 0.001 Up to 14 mg/kg Part 1 (Dose Escalation) Schedule B: Modakafusp alfa TBD Part 1 (Dose Escalation) Schedule C: Modakafusp alfa TBD Part 1 (Dose Escalation) Schedule D: Modakafusp alfa TBD Part 2 (Dose Expansion): Modakafusp alfa TBD + Dexamethasone 40 mg Part 3 (Dose Extension): Modakafusp alfa 120 mg Part 3 (Dose Extension): Modakafusp alfa 240 mg The Part 1 (Dose Escalation) portion of the study will follow a 3+3 dose escalation design to evaluate once-weekly up to 4 different schedules of administration of modakafusp alfa starting at 0.001 mg/kg for dose limiting toxicity (DLT) evaluation and to determine the maximum tolerated dose (MTD) or an optimal biological dose (OBD) for assessments in Part 2. The Part 2 (Dose Expansion) will further assess the safety profile of modakafusp alfa and its efficacy at MTD or OBD. For Part 3 (Dose Extension) participants will be randomized 1:1 to receive single-agent modakafusp alfa 120 mg or 240 mg Q4W. Parts 1 and 2 will be conducted at multiple centers in the United States. Part 3 will be conducted worldwide. The maximum treatment duration in this study is up to 12 months (Parts 1 and 2) or until disease progression (Part 3) and overall time to participate in the study is approximately up to 90 months. Participants with clinical benefit may continue treatment after sponsor approval.

Official Title
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A Phase 1/2 Open-label Study to Investigate the Safety and Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of Modakafusp Alfa (TAK-573) as a Single Agent in Patients With Relapsed Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Modakafusp alfa
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Parts 1 and 2: 1. Has MM defined by the IMWG criteria with evidence of disease progression and: In need of additional myeloma therapy as determined by the investigator. Has previously received at least 3 lines of myeloma therapy (for example, containing an Immunomodulatory imide drug [IMiD], a proteasome inhibitor [PI], an alkylating agent, and/or an anti-CD38 as single agents or in combination). Is either refractory to or intolerant of at least 1 PI and a least 1 IMiD. For Part 3: Has MM defined by the IMWG criteria with evidence of disease progression and: In need of additional myeloma therapy as determined by the investigator. Has previously received at least 3 lines of myeloma therapy. Is refractory to at least 1 IMiD (ie, lenalidomide or pomalidomide [thalidomide excluded]), at least 1 PI (ie, bortezomib, ixazomib, or carfilzomib), and refractory to at least 1 anti-CD38 antibody (ie, daratumumab or isatuximab) and has demonstrated disease progression with the last therapy. Participants who are primary refractory, meaning they never achieved at least a MR with any previous treatment line, are not eligible. For participants in Part 2 and 3 only: Measurable disease is defined as : Serum M-protein ≥500 mg/dL (≥5 g/L) Urine M-protein ≥200 mg/24 hours. Serum free light chain (FLC) assay, with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal. During Part 1 only, participants not meeting the above criteria for measurable disease should, at least, have measurable bone marrow plasmacytosis (greater than or equal to [≥ ] 10 percent [%]) and/or plasmacytoma (≥1 centimeter [cm] in diameter) detected by physical examination or imaging. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. Exclusion Criteria: For Parts 1 and 2: Has polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenstrom macroglobulinemia or immunoglobulin M (IgM) myeloma, or lymphoplasmacytic lymphoma (LPL). Who have received autologous stem cell transplant (SCT) 60 days before first infusion of modakafusp alfa or participants who have received allogeneic SCT 6 months before first infusion. Graft-versus-host disease that is active or requires ongoing systemic immunosuppression. Has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE less than or equal to (≤) Grade 1 or baseline, except for sensory or motor neuropathy which should have recovered to ≤ Grade 2 or baseline. Has clinical signs of central nervous system involvement of MM. For Part 3: Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection (that is, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of HBV DNA levels. Those who are PCR positive will be excluded. In addition to the above criteria, participants must not have plasma cell leukemia or have had primary refractory MM, current central nervous system involvement of MM, myelodysplastic syndrome, myeloproliferative syndrome, or have had a second malignancy within the previous 3 years, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ, resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for which the participant is not on active anticancer therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 (Dose Escalation) Schedule A: Modakafusp alfa 0.001 Up to 14 mg/kg<br>Modakafusp alfa 0.001 up to 14 milligram per kilogram (mg/kg), infusion, intravenously (IV), once every week (Q1W) on Days 1, 8, 15 and 22 of each 28-day treatment cycle up to 2 cycles, followed by once on Days 1 and 15 of each 28-day treatment cycle up to 4 cycles, followed by once on Day 1 of each 28-day treatment cycle until treatment discontinuation. | Drug: Modakafusp alfa<br>* Modakafusp alfa intravenous infusion.<br>* Other names: TEV-48573;|
| Experimental: Part 1 (Dose Escalation) Schedule B: Modakafusp alfa TBD<br>Modakafusp alfa TBD, infusion, IV, once every 2 weeks (Q2W) on Days 1 and 15 of each 28-day treatment cycle until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information. | Drug: Modakafusp alfa<br>* Modakafusp alfa intravenous infusion.<br>* Other names: TEV-48573;|
| Experimental: Part 1 (Dose Escalation) Schedule C: Modakafusp alfa TBD<br>Modakafusp alfa TBD, infusion, IV, once every 3 weeks (Q3W) on Day 1 of each 21-day treatment cycle until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information. | Drug: Modakafusp alfa<br>* Modakafusp alfa intravenous infusion.<br>* Other names: TEV-48573;|
| Experimental: Part 1 (Dose Escalation) Schedule D: Modakafusp alfa TBD<br>Modakafusp alfa TBD, infusion, IV, once every 4 weeks (Q4W) on Day 1 of each 28-day treatment cycle until treatment discontinuation. The starting dose will be decided by the investigators and sponsor representatives based on all available clinical information. | Drug: Modakafusp alfa<br>* Modakafusp alfa intravenous infusion.<br>* Other names: TEV-48573;|
| Experimental: Part 2 (Dose Expansion): Modakafusp alfa TBD + Dexamethasone 40 mg<br>Dose(s) for Phase 2 will be based on safety and tolerability results from the preceding Phase 1 dose escalation cohorts. Participants in Phase 2 cohorts will receive modakafusp alfa TBD as a single agent. Participants in at least 1 cohort will receive modakafusp alfa TBD and modakafusp alfa TBD and dexamethasone 40 mg, orally, once weekly of each 28-day treatment cycle until treatment discontinuation. | Drug: Modakafusp alfa<br>* Modakafusp alfa intravenous infusion.<br>* Other names: TEV-48573;Drug: Dexamethasone<br>* Dexamethasone.<br>|
| Experimental: Part 3 (Dose Extension): Modakafusp alfa 120 mg<br>Participants will receive modakafusp alfa 120 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation. | Drug: Modakafusp alfa<br>* Modakafusp alfa intravenous infusion.<br>* Other names: TEV-48573;|
| Experimental: Part 3 (Dose Extension): Modakafusp alfa 240 mg<br>Participants will receive modakafusp alfa 240 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation. | Drug: Modakafusp alfa<br>* Modakafusp alfa intravenous infusion.<br>* Other names: TEV-48573;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Percentage of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) is defined as any untoward medical occurrence in a participants administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. A TEAE is defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug. | Up to approximately 90 months | 
| Part 1: Percentage of Participants With Dose-limiting Toxicities (DLTs) | DLTs will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0. Nonhematologic TEAEs of NCI CTCAE Grade ≥3 clearly unrelated to the underlying disease and occurring during the first cycle will be considered DLTs. | Up to Cycle 1 (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) | 
| Part 1: Percentage of Participants Reporting one or More Grade 3 TEAEs | TEAEs Grades will be evaluated as per NCI CTCAE, Version 5.0. Grade 1 scaled as Mild; Grade 2 scaled as Moderate; Grade 3 scaled as severe or medically significant but not immediately life-threatening; Grade 4 scaled as life-threatening consequences; and Grade 5 scaled as death related to AE. | Up to approximately 90 months | 
| Part 1: Percentage of Participants Reporting one or More Serious Adverse Events (SAEs) | An SAE is defined as any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is an medically important event that satisfies any of the following: a) May require intervention to prevent items 1 through 5 above. b) May expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization. | Up to approximately 90 months | 
| Part 1: Percentage of Participants Who Discontinue the Treatment Because of TEAE | A TEAE is defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug. | Up to approximately 90 months | 
| Part 1: Percentage of Participants With Dose Modifications: Dose Delay |  | Up to approximately 90 months | 
| Part 1: Percentage of Participants With Dose Modifications: Dose Interruptions |  | Up to approximately 90 months | 
| Part 1: Percentage of Participants With Dose Modifications: Dose Reductions |  | Up to approximately 90 months | 
| Part 1: Percentage of Participants With Clinically Significant Laboratory Values | Laboratory values will include hematology, chemistry, and urine analysis. | Up to approximately 90 months | 
| Part 1: Percentage of Participants With Clinically Significant Vital Signs Measurements | Vital signs will include temperature, pulse, respiratory rate, oxygen saturation, and blood pressure. | Up to approximately 90 months | 
| Part 2: Overall Response Rate (ORR) | ORR is defined as the percentage of participants who achieved a partial response rate (PR) or better during the study as defined by International Myeloma Working Group (IMWG) Uniform Response Criteria. | Up to approximately 90 months | 
| Part 3: Overall Response Rate (ORR) Assessed by Independent Review Committee (IRC) | ORR is defined as the percentage of participants who achieved a PR or better during the study as defined by IMWG Uniform Response Criteria assessed by IRC. | Up to approximately 90 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and 2: Percentage of Participants With Dose-limiting Toxicities (DLTs)- Like Events | Percentage of participants with TEAEs meeting DLT definition that occur after phase (P) 1 Cycle (C) 1 will be reported. Toxicity will be evaluated as per the NCI CTCAE, Version 5.0. The hematologic TEAEs of Grade ≥3 clearly unrelated to the underlying disease and occur during the first cycle that is considered DLTs: Grade ≥3 hemolysis; Grade 4 neutropenia for >7 consecutive days; Grade 4 thrombocytopenia for >14 consecutive days; Grade 3 thrombocytopenia with clinically significant bleeding; Any other Grade ≥4 hematologic toxicity except for Grade 4 lymphopenia. An incomplete recovery from treatment-related toxicity causing >2-week delay in the next scheduled infusion before the initiation of C2 will be considered a DLT. Frequencies and other TEAEs occur over the course of extended treatment with study drug, including dose modification, treatment discontinuation, and clinically significant laboratory values and vital signs. | Up to approximately 90 months | 
| Part 1: Cmax: Maximum Observed Serum Concentration for Modakafusp alfa | PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days). | Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) | 
| Part 1: Tmax: Time to Reach the Cmax for Modakafusp alfa | PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days). | Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) | 
| Part 1: AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa | PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days). | Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) | 
| Part 1: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Modakafusp alfa | PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days). | A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) | 
| Part 1: λz: Terminal Disposition Rate Constant for Modakafusp alfa | PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days). | Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) | 
| Part 1: T1/2: Terminal Elimination Half-life for Modakafusp alfa | PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days). | Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) | 
| Part 1: CL: Clearance for Modakafusp alfa | PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days). | Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) | 
| Part 1: Vss: Volume of Distribution at Steady State for Modakafusp alfa | PK blood samples will be collected at the following time points for schedule A: Pre-infusion and at multiple time points (up to 72 hour [h]) C1-2 D1, 15; up to 4h C1-2 D8, 22 and C2 D15; up to 24h C3 D1; up to 4h on C3, 4-6 D15, D1, C4-6 and C7-13 D1; Schedule B: Pre-infusion and at multiple time points (up to 24h) on C1-2 D1, 15; up to 24h C3 D1; up to 4h C3 D15 and C4-13 D1; Schedule C: Pre-infusion and at multiple time points (up to 336h) on C1-2 D1; up to 4h on C3-17 D1; Schedule D: Pre-infusion and at multiple time points (up to 504h) C1-2 D1; up to 4h C3-13 D1 post-infusion (Schedule A, B and D cycle is 28 days and schedule C cycle is 21 days). | Schedule A Cycle(C)1-13,Day(D)1,8,15,22; Schedule B C1-13,D1,15; Schedule C C1-17,D1; Schedule D C1-13,D1: Pre-infusion and at multiple times post-infusion (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) | 
| Parts 1, 2 and 3: Percentage of Participants with Positive Anti-drug Antibodies (ADA) |  | Up to approximately 90 months | 
| Part 1: Objective Response Rate (ORR) | ORR is defined as the percentage of participants who achieved a PR or better during the study as defined by IMWG Uniform Response Criteria. | Up to approximately 90 months | 
| Parts 1 and 2: Clinical Benefit Rate (CBR) | CBR is defined as the percentage of participants who achieved MR or better during the study as defined by IMWG Uniform Response Criteria. | Up to approximately 90 months | 
| Parts 1 and 2: Disease Control Rate (DCR) | DCR is defined as the percentage of participants who achieved a stable disease (SD) or better during the study as defined by IMWG Uniform Response Criteria. | Up to approximately 90 months | 
| Parts 1, 2 and 3: Duration of Response (DOR) | DOR is defined as the time from the date of first documentation of response PR or better to the time of disease progression or death, whichever occurs first. | Up to approximately 90 months | 
| Parts 1 and 2: Time to Response | Time to response is defined as the time from first dose to the date of first documentation of response (PR or better). | Up to approximately 90 months | 
| Parts 1, 2 and 3: Progression Free Survival (PFS) | PFS is defined as the time from the date of enrollment until the date of PD or death due to any cause, whichever occurs first as defined by IMWG Criteria. | Up to approximately 90 months | 
| Parts 2 and 3: Overall Survival (OS) |  | Up to approximately 90 months | 
| Part 2: Cmax: Maximum Observed Serum Concentration for Modakafusp alfa |  | Up to approximately 90 months | 
| Part 2: AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa |  | Up to approximately 90 months | 
| Part 2: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Modakafusp alfa |  | Up to approximately 90 months | 
| Part 2: λz: Terminal Disposition Rate Constant for Modakafusp alfa |  | Up to approximately 90 months | 
| Part 2: Tmax: Time to Reach the Cmax for Modakafusp alfa |  | Up to approximately 90 months | 
| Part 2: CL: Clearance for Modakafusp alfa |  | Up to approximately 90 months | 
| Part 2: Vss: Volume of Distribution at Steady State for Modakafusp alfa |  | Up to approximately 90 months | 
| Part 2: T1/2z: Terminal Elimination Half-life for Modakafusp alfa |  | Up to approximately 90 months | 
| Part 3: Objective Response Rate (ORR) by Investigator Assessment | ORR is defined as the percentage of participants who achieved a PR or better during the study as defined by IMWG Uniform Response Criteria assessed by investigators. | Up to approximately 90 months | 
| Part 3: Clinical Benefit Rate (CBR) by IRC and Investigator assessment | CBR is defined as the percentage of participants who achieved MR or better during the study as defined by IMWG Uniform Response Criteria. | Up to approximately 90 months | 
| Part 3: Duration of Clinical Benefit | Duration of clinical benefit is defined as the time from first documented evidence of confirmed MR or better until the earliest date of a confirmed PD per IMWG, or death among patients who achieve a confirmed MR or better. | Up to approximately 90 months | 
| Part 3: Disease Control Rate (DCR) by IRC and Investigator Assessment | DCR is defined as the percentage of participants who achieved a stable disease (SD) or better during the study as defined by IMWG Uniform Response Criteria. | Up to approximately 90 months | 
| Part 3: Duration of Disease Control | Duration of disease control is defined as the time from first documented evidence of SD or better until the earliest date of a confirmed PD per IMWG, or death among patients who achieve a SD or better. | Up to approximately 90 months | 
| Part 3: Time to Progression (TTP) by IRC and Investigator Assessment | TTP is defined as the time from the date of the first dose until the earliest date of confirmed PD per IMWG, or death due to PD. | Up to approximately 90 months | 
| Part 3: Rate of Minimal Residual Disease (MRD) Negativity Status at a Sensitivity of 10^-5 in Participants Achieving CR | MRD negativity at a sensitivity of 10^-5 is defined as patients who are MRD negative at a sensitivity of 10^-5 in patients achieving suspected complete response (CR). CR is defined as negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow; in participants for whom only measurable disease is by serum FLC level, normal FLC ratio of 0.26 to 1.65 in addition to CR criteria is required. | Up to approximately 90 months | 
| Part 3:Duration of MRD Negativity Status at a Sensitivity of 10^-5 in Participants Achieving CR | Duration of MRD negativity (10^-5) is defined as the time from the first MRD negative status (10^-5) to the earliest date of the MRD positive status (10^-5), confirmed PD per IMWG or death. | Up to approximately 90 months | 
| Part 3: Percentage of Participants With Adverse Events (AEs) | An adverse event (AE) is defined as any untoward medical occurrence in a participants administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. | Up to approximately 90 months | 
| Part 3: Percentage of Participants With Serious Adverse Events (SAEs) | An SAE is defined as any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is an medically important event that satisfies any of the following: a) May require intervention to prevent items 1 through 5 above. b) May expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization. | Up to approximately 90 months | 
| Part 3: Percentage of Participants With Clinically Significant Laboratory Values | Laboratory values will include hematology, chemistry, and urine analysis. | Up to approximately 90 months | 
| Part 3: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Status | ECOG is a grade, where grade 0: Normal activity. Grade 1: Symptoms but ambulatory. Grade 2: In bed <50% of the time. Grade 3: In bed >50% of the time. Grade 4: 100% bedridden. Grade 5: Dead. | Up to approximately 90 months | 
| Part 3: Health Care Utilization: Length of Hospital Stays |  | Up to approximately 90 months | 
| Part 3: Percentage of Participants With Neutralizing Antibodies (NAb) |  | Up to approximately 90 months | 
| Part 3: Health Care Utilization: Number of Participants With at Least One Medical Encounter | Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits. | Up to approximately 90 months | 
| Part 3: Patient-reported Outcome (PRO): Instrument European Organisation for Research and Treatment of Cancer QLQ Questionnaire Multiple Myeloma Module (EORTC QLQ-MY20) | The EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image and future perspective), and 2 symptoms scales (disease symptoms and side effects of treatment). The QLQ-MY20 raw scores are converted into scale scores ranging from 0 to 100. For the symptom scales, lower scores represent better functioning. All items in this questionnaire have a recall period of 1 week. | Up to approximately 90 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy