A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma
- Registration Number
- NCT03215030
- Lead Sponsor
- Takeda
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 272
For Parts 1 and 2:
- 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:
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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.
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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.
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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.
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Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1 (Dose Escalation) Schedule A: Modakafusp alfa 0.001 Up to 14 mg/kg Modakafusp alfa 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. Part 1 (Dose Escalation) Schedule B: Modakafusp alfa TBD Modakafusp alfa 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. Part 1 (Dose Escalation) Schedule C: Modakafusp alfa TBD Modakafusp alfa 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. Part 1 (Dose Escalation) Schedule D: Modakafusp alfa TBD Modakafusp alfa 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. Part 2 (Dose Expansion): Modakafusp alfa TBD + Dexamethasone 40 mg Modakafusp alfa 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. Part 2 (Dose Expansion): Modakafusp alfa TBD + Dexamethasone 40 mg Dexamethasone 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. Part 3 (Dose Extension): Modakafusp alfa 120 mg Modakafusp alfa Participants will receive modakafusp alfa 120 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation. Part 3 (Dose Extension): Modakafusp alfa 240 mg Modakafusp alfa Participants will receive modakafusp alfa 240 mg, infusion, IV, Q4W, for each 28-day treatment cycle until disease progression or treatment discontinuation.
- Primary Outcome Measures
Name Time Method Part 1: Percentage of Participants Reporting one or More Grade 3 TEAEs Up to approximately 90 months 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.
Part 1: Percentage of Participants Reporting one or More Serious Adverse Events (SAEs) Up to approximately 90 months 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.
Part 1: Percentage of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs) Up to approximately 90 months 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.
Part 1: Percentage of Participants With Dose-limiting Toxicities (DLTs) Up to Cycle 1 (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C) 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.
Part 1: Percentage of Participants With Dose Modifications: Dose Delay Up to approximately 90 months Part 3: Overall Response Rate (ORR) Assessed by Independent Review Committee (IRC) Up to approximately 90 months 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.
Part 1: Percentage of Participants With Clinically Significant Laboratory Values Up to approximately 90 months Laboratory values will include hematology, chemistry, and urine analysis.
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 Vital Signs Measurements Up to approximately 90 months Vital signs will include temperature, pulse, respiratory rate, oxygen saturation, and blood pressure.
Part 2: Overall Response Rate (ORR) Up to approximately 90 months 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.
Part 1: Percentage of Participants Who Discontinue the Treatment Because of TEAE Up to approximately 90 months 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.
- Secondary Outcome Measures
Name Time Method Part 1 and 2: Percentage of Participants With Dose-limiting Toxicities (DLTs)- Like Events Up to approximately 90 months 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.
Part 1: Cmax: Maximum Observed Serum Concentration for Modakafusp alfa 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) 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).
Part 1: Tmax: Time to Reach the Cmax for Modakafusp alfa 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) 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).
Part 1: AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa 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) 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).
Part 1: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Modakafusp alfa 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) 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).
Part 1: λz: Terminal Disposition Rate Constant for Modakafusp alfa 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) 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).
Part 1: T1/2: Terminal Elimination Half-life for Modakafusp alfa 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) 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).
Part 1: CL: Clearance for Modakafusp alfa 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) 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).
Part 1: Vss: Volume of Distribution at Steady State for Modakafusp alfa 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) 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).
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) Up to approximately 90 months ORR is defined as the percentage of participants who achieved a PR or better during the study as defined by IMWG Uniform Response Criteria.
Parts 1, 2 and 3: Progression Free Survival (PFS) Up to approximately 90 months 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.
Parts 1 and 2: Clinical Benefit Rate (CBR) Up to approximately 90 months CBR is defined as the percentage of participants who achieved MR or better during the study as defined by IMWG Uniform Response Criteria.
Parts 1 and 2: Disease Control Rate (DCR) Up to approximately 90 months 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.
Parts 1, 2 and 3: Duration of Response (DOR) Up to approximately 90 months 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.
Parts 1 and 2: Time to Response Up to approximately 90 months Time to response is defined as the time from first dose to the date of first documentation of response (PR or better).
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: Clinical Benefit Rate (CBR) by IRC and Investigator assessment Up to approximately 90 months CBR is defined as the percentage of participants who achieved MR or better during the study as defined by IMWG Uniform Response Criteria.
Part 3: Objective Response Rate (ORR) by Investigator Assessment Up to approximately 90 months 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.
Part 3: Disease Control Rate (DCR) by IRC and Investigator Assessment Up to approximately 90 months 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.
Part 3: Percentage of Participants With Neutralizing Antibodies (NAb) Up to approximately 90 months Part 3: Duration of Clinical Benefit Up to approximately 90 months 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.
Part 3: Duration of Disease Control Up to approximately 90 months 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.
Part 3: Time to Progression (TTP) by IRC and Investigator Assessment Up to approximately 90 months 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.
Part 3:Duration of MRD Negativity Status at a Sensitivity of 10^-5 in Participants Achieving CR Up to approximately 90 months 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.
Part 3: Percentage of Participants With Adverse Events (AEs) Up to approximately 90 months 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.
Part 3: Percentage of Participants With Serious Adverse Events (SAEs) Up to approximately 90 months 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.
Part 3: Percentage of Participants With Clinically Significant Laboratory Values Up to approximately 90 months Laboratory values will include hematology, chemistry, and urine analysis.
Part 3: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Status Up to approximately 90 months 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.
Part 3: Rate of Minimal Residual Disease (MRD) Negativity Status at a Sensitivity of 10^-5 in Participants Achieving CR Up to approximately 90 months 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.
Part 3: Health Care Utilization: Length of Hospital Stays Up to approximately 90 months Part 3: Health Care Utilization: Number of Participants With at Least One Medical Encounter Up to approximately 90 months Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits.
Part 3: Patient-reported Outcome (PRO): Instrument European Organisation for Research and Treatment of Cancer QLQ Questionnaire Multiple Myeloma Module (EORTC QLQ-MY20) Up to approximately 90 months 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.
Trial Locations
- Locations (94)
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Lumi Research
🇺🇸Houston, Texas, United States
University College London Hospitals NHS Foundation Trust
🇬🇧London, England, United Kingdom
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, England, United Kingdom
Royal Cornwall Hospital NHS Trust
🇬🇧Cornwell, England, United Kingdom
Oslo Universitetssykehus-Ulleval Hospital
🇳🇴Oslo, Norway
British Columbia Cancer Agency Vancouver Centre
🇨🇦Vancouver, British Columbia, Canada
Institut de cancerologie Strasbourg Europe
🇫🇷Strasbourg, Alsace, France
University of Rochester
🇺🇸Rochester, New York, United States
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, England, United Kingdom
Nanjing Drum Tower Hospital
🇨🇳Nanjing, Jiangsu, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, Tianjin, China
The First Affiliated Hospital, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Office of James R. Berenson MD
🇺🇸West Hollywood, California, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Levine Cancer Center
🇺🇸Charlotte, North Carolina, United States
Baptist Cancer Center - Memphis - Walnut Grove
🇺🇸Memphis, Tennessee, United States
Sir Mortimer B. Davis Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Sun Yat-Sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
Wuhan Union Hospital
🇨🇳Wuhan, Hubei, China
The First Affiliated Hospital of Soochow University - Suzhou First People's Hospital
🇨🇳Suzhou, Jiangsu, China
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Centre Hospitalier Universitaire Henri Mondor
🇫🇷Creteil Cedex, Ile-de-france, France
Hopital Saint-Antoine
🇫🇷Paris Cedex 12, Ile-de-france, France
Hopital Necker-Enfants Malades
🇫🇷Paris, Ile-de-france, France
Centre Hospitalier d'Argenteuil - Centre Hospitalier Victor Dupouy
🇫🇷Argenteuil Cedex, France
Centre Hospitalier Universitaire de Poitiers
🇫🇷Poitiers, Poitou-charentes, France
Universitatsklinik Tubingen
🇩🇪Tuebingen, Baden-wuerttemberg, Germany
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Universitatsklinikum Leipzig
🇩🇪Leipzig, Sachsen, Germany
The Chaim Sheba Medical Center
🇮🇱Ramat Gan, Tel Aviv, Israel
Evaggelismos General Hospital
🇬🇷Athens, Attica, Greece
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Azienda Ospedaliero-Universitaria di Bologna - Policlinico Sant'Orsola-Malpighi
🇮🇹Bologna, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
🇮🇹Ancona, Italy
Nagoya City University Hospital
🇯🇵Nagoya, Aichi, Japan
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Jeollanam-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Espanol Auxilio Mutuo
🇵🇷San Juan, Puerto Rico
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Ad-Vance Medical Research
🇵🇷Ponce, Puerto Rico
Hospital Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Genesis Care Windsor - Genesis Care UK Ltd.
🇬🇧Windsor, England, United Kingdom
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
June E. Nylen Cancer Center
🇺🇸Sioux City, Iowa, United States
Centre Hospitalier Universitaire de Toulouse Hopital Purpan
🇫🇷Toulouse, Midi-pyrenees, France
Los Angeles Cancer Network - Glendale Adventist Medical Center
🇺🇸Glendale, California, United States
John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
Northwestern Medicine - Northwestern Medical Group
🇺🇸Chicago, Illinois, United States
Investigative Clinical Research of Indiana, LLC
🇺🇸Noblesville, Indiana, United States
Levine Cancer Institute - Concord
🇺🇸Concord, North Carolina, United States
Centre de Recherche du CHUM
🇨🇦Montreal, Quebec, Canada
Peking University People's Hospital
🇨🇳Beijing, Beijing, China
Shanghai Fourth People's Hospital
🇨🇳Shanghai, Shanghai, China
Centre Hospitalier Regional Universitaire de Lille
🇫🇷Lille Cedex, NORD Pas-de-calais, France
Hopital Saint-Vincent de Paul - Lille
🇫🇷Lille Cedex, NORD Pas-de-calais, France
Centre Hospitalier Universitaire Nantes - Hotel Dieu
🇫🇷Nantes Cedex 1, PAYS DE LA Loire, France
AON SS Antonio e Biagio e Cesare Arrigo
🇮🇹Alessandria, Italy
Alexandra General Hospital of Athens
🇬🇷Athens, Attica, Greece
University Regional General Hospital of Patras
🇬🇷Patra, Peloponnese, Greece
Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele
🇮🇹Catania, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Ogaki Municipal Hospital
🇯🇵Gifu-shi, Gifu, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto-City, Kyoto, Japan
National Hospital Organization Okayama Medical Center
🇯🇵Okayama-city, Okayama, Japan
Japanese Red Cross Medical Center
🇯🇵Tokyo, Japan
The Catholic University of Korea - Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Tri-Service General Hospital
🇨🇳Taipei, Taipei CITY, Taiwan
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Ondokuz Mayis Universitesi Tp Fakultesi
🇹🇷Samsun, Turkey
Ankara Universitesi
🇹🇷Yenimahalle, Ankara, Turkey
Genesis Care - Milton Keynes
🇬🇧Milton Keynes, England, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧Sutton, England, United Kingdom
Univeristy of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
USOR - Comprehensive Cancer Centers of Nevada - Central Valley
🇺🇸Las Vegas, Nevada, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Smilow Cancer Hospital at Yale New Haven
🇺🇸New Haven, Connecticut, United States
University of California Irvine
🇺🇸Orange, California, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States