Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
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 |
|
| Primary |
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) |
|
| Primary |
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 |
|
| Primary |
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 |
|
| Primary |
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 |
|
| Primary |
Part 1: Percentage of Participants With Dose Modifications: Dose Delay |
|
Up to approximately 90 months |
|
| Primary |
Part 1: Percentage of Participants With Dose Modifications: Dose Interruptions |
|
Up to approximately 90 months |
|
| Primary |
Part 1: Percentage of Participants With Dose Modifications: Dose Reductions |
|
Up to approximately 90 months |
|
| Primary |
Part 1: Percentage of Participants With Clinically Significant Laboratory Values |
Laboratory values will include hematology, chemistry, and urine analysis. |
Up to approximately 90 months |
|
| Primary |
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 |
|
| Primary |
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 |
|
| Primary |
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 |
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 |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
Part 1: AUC8: 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) |
|
| Secondary |
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) |
|
| Secondary |
Part 1: ?z: 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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
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) |
|
| Secondary |
Parts 1, 2 and 3: Percentage of Participants with Positive Anti-drug Antibodies (ADA) |
|
Up to approximately 90 months |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
Parts 2 and 3: Overall Survival (OS) |
|
Up to approximately 90 months |
|
| Secondary |
Part 2: Cmax: Maximum Observed Serum Concentration for Modakafusp alfa |
|
Up to approximately 90 months |
|
| Secondary |
Part 2: AUC8: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa |
|
Up to approximately 90 months |
|
| Secondary |
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 |
|
| Secondary |
Part 2: ?z: Terminal Disposition Rate Constant for Modakafusp alfa |
|
Up to approximately 90 months |
|
| Secondary |
Part 2: Tmax: Time to Reach the Cmax for Modakafusp alfa |
|
Up to approximately 90 months |
|
| Secondary |
Part 2: CL: Clearance for Modakafusp alfa |
|
Up to approximately 90 months |
|
| Secondary |
Part 2: Vss: Volume of Distribution at Steady State for Modakafusp alfa |
|
Up to approximately 90 months |
|
| Secondary |
Part 2: T1/2z: Terminal Elimination Half-life for Modakafusp alfa |
|
Up to approximately 90 months |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
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 |
|
| Secondary |
Part 3: Percentage of Participants With Clinically Significant Laboratory Values |
Laboratory values will include hematology, chemistry, and urine analysis. |
Up to approximately 90 months |
|
| Secondary |
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 |
|
| Secondary |
Part 3: Health Care Utilization: Length of Hospital Stays |
|
Up to approximately 90 months |
|
| Secondary |
Part 3: Percentage of Participants With Neutralizing Antibodies (NAb) |
|
Up to approximately 90 months |
|
| Secondary |
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 |
|
| Secondary |
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 |
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