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.
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.
Brief Title
A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Multiple Myeloma
Eligibility Criteria
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:
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.
* 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.
2. For participants in Part 2 and 3 only: Measurable disease is defined as :
1. Serum M-protein ≥500 mg/dL (≥5 g/L)
2. Urine M-protein ≥200 mg/24 hours.
3. Serum free light chain (FLC) assay, with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
Exclusion Criteria:
For Parts 1 and 2:
1. 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).
2. 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.
3. 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.
4. 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.
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:
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.
* 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.
2. For participants in Part 2 and 3 only: Measurable disease is defined as :
1. Serum M-protein ≥500 mg/dL (≥5 g/L)
2. Urine M-protein ≥200 mg/24 hours.
3. Serum free light chain (FLC) assay, with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
Exclusion Criteria:
For Parts 1 and 2:
1. 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).
2. 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.
3. 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.
4. 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.
Inclusion Criteria
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:
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.
* 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.
2. For participants in Part 2 and 3 only: Measurable disease is defined as :
1. Serum M-protein ≥500 mg/dL (≥5 g/L)
2. Urine M-protein ≥200 mg/24 hours.
3. Serum free light chain (FLC) assay, with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
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:
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.
* 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.
2. For participants in Part 2 and 3 only: Measurable disease is defined as :
1. Serum M-protein ≥500 mg/dL (≥5 g/L)
2. Urine M-protein ≥200 mg/24 hours.
3. Serum free light chain (FLC) assay, with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
Gender
All
Gender Based
false
Keywords
Drug Therapy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03215030
Org Class
Industry
Org Full Name
Takeda
Org Study Id
TAK-573-1501
Overall Status
Completed
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Part 1: Percentage of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs)
Outcome Time Frame
Up to approximately 90 months
Outcome Description
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.
Outcome Measure
Part 1: Percentage of Participants With Dose-limiting Toxicities (DLTs)
Outcome Time Frame
Up to Cycle 1 (cycle length is 28 days for Schedule A, B and D; 21 days for Schedule C)
Outcome Description
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.
Outcome Measure
Part 1: Percentage of Participants Reporting one or More Grade 3 TEAEs
Outcome Time Frame
Up to approximately 90 months
Outcome Description
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.
Outcome Measure
Part 1: Percentage of Participants Reporting one or More Serious Adverse Events (SAEs)
Outcome Time Frame
Up to approximately 90 months
Outcome Description
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.
Outcome Measure
Part 1: Percentage of Participants Who Discontinue the Treatment Because of TEAE
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 1: Percentage of Participants With Dose Modifications: Dose Delay
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 1: Percentage of Participants With Dose Modifications: Dose Interruptions
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 1: Percentage of Participants With Dose Modifications: Dose Reductions
Outcome Time Frame
Up to approximately 90 months
Outcome Description
Laboratory values will include hematology, chemistry, and urine analysis.
Outcome Measure
Part 1: Percentage of Participants With Clinically Significant Laboratory Values
Outcome Time Frame
Up to approximately 90 months
Outcome Description
Vital signs will include temperature, pulse, respiratory rate, oxygen saturation, and blood pressure.
Outcome Measure
Part 1: Percentage of Participants With Clinically Significant Vital Signs Measurements
Outcome Time Frame
Up to approximately 90 months
Outcome Description
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.
Outcome Measure
Part 2: Overall Response Rate (ORR)
Outcome Time Frame
Up to approximately 90 months
Outcome Description
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.
Outcome Measure
Part 3: Overall Response Rate (ORR) Assessed by Independent Review Committee (IRC)
Outcome Time Frame
Up to approximately 90 months
Secondary Ids
Secondary Id
TV48573-ONC-10128
Secondary Id
U1111-1195-8134
Secondary Id
2021-006038-37
Secondary Id
jRCT2061220078
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 1 and 2: Percentage of Participants With Dose-limiting Toxicities (DLTs)- Like Events
Outcome Description
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).
Outcome Time Frame
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)
Outcome Measure
Part 1: Cmax: Maximum Observed Serum Concentration for Modakafusp alfa
Outcome Description
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).
Outcome Time Frame
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)
Outcome Measure
Part 1: Tmax: Time to Reach the Cmax for Modakafusp alfa
Outcome Description
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).
Outcome Time Frame
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)
Outcome Measure
Part 1: AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa
Outcome Description
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).
Outcome Time Frame
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)
Outcome Measure
Part 1: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Modakafusp alfa
Outcome Description
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).
Outcome Time Frame
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)
Outcome Measure
Part 1: λz: Terminal Disposition Rate Constant for Modakafusp alfa
Outcome Description
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).
Outcome Time Frame
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)
Outcome Measure
Part 1: T1/2: Terminal Elimination Half-life for Modakafusp alfa
Outcome Description
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).
Outcome Time Frame
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)
Outcome Measure
Part 1: CL: Clearance for Modakafusp alfa
Outcome Description
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).
Outcome Time Frame
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)
Outcome Measure
Part 1: Vss: Volume of Distribution at Steady State for Modakafusp alfa
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Parts 1, 2 and 3: Percentage of Participants with Positive Anti-drug Antibodies (ADA)
Outcome Description
ORR is defined as the percentage of participants who achieved a PR or better during the study as defined by IMWG Uniform Response Criteria.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 1: Objective Response Rate (ORR)
Outcome Description
CBR is defined as the percentage of participants who achieved MR or better during the study as defined by IMWG Uniform Response Criteria.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Parts 1 and 2: Clinical Benefit Rate (CBR)
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Parts 1 and 2: Disease Control Rate (DCR)
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Parts 1, 2 and 3: Duration of Response (DOR)
Outcome Description
Time to response is defined as the time from first dose to the date of first documentation of response (PR or better).
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Parts 1 and 2: Time to Response
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Parts 1, 2 and 3: Progression Free Survival (PFS)
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Parts 2 and 3: Overall Survival (OS)
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 2: Cmax: Maximum Observed Serum Concentration for Modakafusp alfa
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 2: AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 2: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Modakafusp alfa
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 2: λz: Terminal Disposition Rate Constant for Modakafusp alfa
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 2: Tmax: Time to Reach the Cmax for Modakafusp alfa
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 2: CL: Clearance for Modakafusp alfa
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 2: Vss: Volume of Distribution at Steady State for Modakafusp alfa
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 2: T1/2z: Terminal Elimination Half-life for Modakafusp alfa
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Objective Response Rate (ORR) by Investigator Assessment
Outcome Description
CBR is defined as the percentage of participants who achieved MR or better during the study as defined by IMWG Uniform Response Criteria.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Clinical Benefit Rate (CBR) by IRC and Investigator assessment
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Duration of Clinical Benefit
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Disease Control Rate (DCR) by IRC and Investigator Assessment
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Duration of Disease Control
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Time to Progression (TTP) by IRC and Investigator Assessment
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Rate of Minimal Residual Disease (MRD) Negativity Status at a Sensitivity of 10^-5 in Participants Achieving CR
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3:Duration of MRD Negativity Status at a Sensitivity of 10^-5 in Participants Achieving CR
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Percentage of Participants With Adverse Events (AEs)
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Percentage of Participants With Serious Adverse Events (SAEs)
Outcome Description
Laboratory values will include hematology, chemistry, and urine analysis.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Percentage of Participants With Clinically Significant Laboratory Values
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Status
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Health Care Utilization: Length of Hospital Stays
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Percentage of Participants With Neutralizing Antibodies (NAb)
Outcome Description
Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Health Care Utilization: Number of Participants With at Least One Medical Encounter
Outcome Description
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.
Outcome Time Frame
Up to approximately 90 months
Outcome Measure
Part 3: Patient-reported Outcome (PRO): Instrument European Organisation for Research and Treatment of Cancer QLQ Questionnaire Multiple Myeloma Module (EORTC QLQ-MY20)
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Nishi Shah
Investigator Email
nisshah@montefiore.org