Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Phase 1: Number of Participants with Dose Limiting Toxicities (DLT) |
DLT will be defined as any of the TEAEs that occur during Cycle 1 and are considered by the investigator to be at least possibly related to modakafusp alfa. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. |
Cycle 1 (cycle length=28 days) |
|
| Primary |
Phase 1: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Per Severity |
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Severity grades for TEAEs will be evaluated as per the NCI CTCAE Version 5.0. |
Up to 60 months |
|
| Primary |
Phase 2a: Overall Response Rate (ORR) |
ORR is defined as the percentage of participants who achieve a confirmed partial response (PR) or better during the study in the safety population. ORR will be assessed by the investigator per International Myeloma Working Group (IMWG) criteria. |
Up to 60 months |
|
| Secondary |
Phase 1: Cmax: Single-Dose Maximum Observed Serum Concentration for Modakafusp Alfa |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: Tmax: Time to First Occurrence of Maximum Serum Concentration (Cmax) for Modakafusp Alfa |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: AUC8: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Modakafusp Alfa |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to Time of the Last Quantifiable Concentration |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: Apparent Serum Terminal Disposition Rate Constant for Modakafusp Alfa |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: Apparent Serum Terminal Disposition Phase Half-life for Modakafusp Alfa |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: Total Clearance After Intravenous Administration for Modakafusp Alfa |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: Volume of Distribution at Steady State After Intravenous Administration for Modakafusp Alfa |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: Cmax: Single-Dose Maximum Observed Serum Concentration for Daratumumab |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: Tmax: Time to First Occurrence of Maximum Serum Concentration (Cmax) for Daratumumab |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: Ctrough: Single-Dose and Multiple-dose Observed Concentration at the End of a Dosing Interval for Daratumumab |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: AUC8: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Daratumumab |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to Time of the Last Quantifiable Concentration for Daratumumab |
|
Days 1, 8, 15, and 22 of Cycles 1 and 2: Pre-dose, and at multiple time points up to 4 hours post-dose; Day 2 of Cycles 1 and 2: Post-dose (cycle length=28 days) |
|
| Secondary |
Phase 1: Overall Response Rate (ORR) |
ORR is defined as the percentage of participants who achieved a confirmed PR or better during the study in the safety population. ORR will be assessed by the investigator per IMWG criteria. |
Up to 60 months |
|
| Secondary |
Phase 1 and Phase 2a: Duration of Response (DOR) |
DOR is defined as the time from the date of first documentation of a confirmed PR or better to the date of first documentation of confirmed progressive disease or death due to any cause, whichever occurs first. DOR will be calculated for confirmed responders only (PR or better). DOR will be assessed by the investigator as per IMWG criteria. |
Up to 60 months |
|
| Secondary |
Phase 1 and Phase 2a: Progression Free Survival (PFS) |
PFS is defined as the time from the date of the first dose administration of any study drug to the first documentation of confirmed progressive disease or death due to any cause, whichever occurs first. PFS will be assessed by the investigator as per IMWG criteria. |
up to 60 months |
|
| Secondary |
Phase 1 and Phase 2a: Overall Survival (OS) |
OS is defined as the time from the date of the first dose administration of any study drug to the documentation of death due to any cause. OS will be assessed by the investigator as per IMWG criteria. |
Up to 60 months |
|
| Secondary |
Phase 1 and Phase 2a: Number of Participants With Anti-drug Antibodies |
|
Up to 60 months |
|
| Secondary |
Phase 1 and Phase 2a: Titer of Anti-drug Antibodies |
|
Up to 60 months |
|
| Secondary |
Phase 1 and Phase 2a: Number of Participants With Neutralizing Antibodies (NAb) Against Study Drug |
|
Up to 60 months |
|
| Secondary |
Phase 1 and Phase 2a: Rate of Measurable [Minimal] Residual Disease Negative (MRD[-]) Complete Response (CR) |
MRD[-] CR rate is defined as the percentage of participants who achieve confirmed CR assessed by the investigator and MRD[-] status using a threshold of 10^-5. The analysis will be based on the response-evaluable population. |
Up to 60 months |
|
| Secondary |
Phase 1 and Phase 2a: Duration of Measurable [Minimal] Residual Disease (MRD) Negativity |
Duration of MRD negativity for participants achieving MRD negativity is defined as the time from the date of first documentation of MRD negativity to the first documentation of MRD positivity or confirmed progressive disease, whichever occurs first. It will be calculated for participants achieving MRD negativity only. |
Up to 60 months |
|
| Secondary |
Phase 2a: Clinical Benefit Rate (CBR) |
CBR is defined as the percentage of participants who had a confirmed response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or minimal response based on investigators' disease assessment per IMWG criteria. |
Up to 60 months |
|
| Secondary |
Phase 2a: Duration of Clinical Benefit (DCB) |
DCB is defined as the time from the date of first documentation of a minimal response or better to the date of first documentation of confirmed progressive disease or death due to any cause, whichever occurs first. DCB will be calculated for only participants who achieved a minimal response or better. DCB will be assessed by the investigator as per IMWG criteria. |
Up to 60 months |
|
| Secondary |
Phase 2a: Disease Control Rate (DCR) |
DCR is defined as the percentage of participants with a confirmed response of sCR, CR, VGPR, PR, minimal response, or stable disease (SD) based on investigators' disease assessment per IMWG criteria. |
Up to 60 months |
|
| Secondary |
Phase 2a: Duration of Disease Control |
Duration of disease control is defined as the time from date of first documentation of SD or better to the date of first documentation of confirmed progressive disease or death due to any cause. Duration of disease control will be calculated for only patients who achieved SD or better. It will be assessed by the investigator per IMWG criteria. |
Up to 60 months |
|
| Secondary |
Phase 2a: Time to Progression (TTP) |
TTP is defined as the time from the date of randomization to the first documentation of confirmed progressive disease as defined by IMWG criteria, assessed by the investigator. Participants without documentation of confirmed progression will be censored at the date of last adequate disease assessment. The analysis will be based on the intent-to-treat (ITT) population. |
Up to 60 months |
|
| Secondary |
Phase 2a: Time to Response (TTR) |
TTR is defined as time from the date of first dose administration of any study drug to the date of the first documentation of a confirmed PR or better. TTR will be calculated for responders only. TTR will be assessed by the investigator per IMWG criteria. |
Up to 60 months |
|
| Secondary |
Phase 2a: Time to Next Treatment (TTNT) |
TTNT is defined as the time from the date of first dose administration of any study drug to the date of the first dose initiation of the next line of anticancer therapy for any reason or death from any cause, whichever comes first. Participants who have not started the next-line therapy will be censored at the date last known to be alive before subsequent anticancer therapy. |
Up to 60 months |
|
| Secondary |
Phase 2a: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Per Severity |
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Severity grades for TEAEs will be evaluated as per the NCI CTCAE Version 5.0. |
Up to 60 months |
|
