Multiple Myeloma
Conditions
Keywords
Drug Therapy
Brief summary
The main aim of this study is to determine safety and tolerability of modakafusp alfa given together with daratumumab to find out the best treatment dose. Another aim of this study is to learn more about the characteristics of modakafusp alfa.
Detailed description
The drug being tested in this study is called modakafusp alfa (TAK-573). Modakafusp alfa is being tested to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy in combination with daratumumab in participants with relapsed or refractory multiple myeloma (RRMM). The study will consist of 2 phases: Phase 1 Dose Escalation and a Phase 2a Dose Finding. The study will enroll approximately 58 patients. Approximately 18 participants will be enrolled in the Phase 1 Dose Escalation/De-escalation and two dose levels of modakafusp alfa in combination with daratumumab SC will be selected to be further explored in the randomized Phase 2a Dose Finding part of the study wherein, approximately 40 participants will be randomly assigned by chance (like flipping a coin) to one of the two treatment groups: * Phase 2a Dose Finding: Modakafusp Alfa (DL1) + Daratumumab * Phase 2a Dose Finding: Modakafusp Alfa (DL2) + Daratumumab This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 60 months. Participants who discontinue study drug treatment for reasons other than progressive disease will continue progression-free survival (PFS) follow-up every 4 weeks from the end of treatment (EOT) visit until the occurrence of progressive disease, death, the start of subsequent systemic antineoplastic therapy, study termination, whichever occurs first.
Interventions
DRUGModakafusp Alfa
Modakafusp alfa intravenous infusion
DRUGDaratumumab
Daratumumab SC injection
Sponsors
Teva Branded Pharmaceutical Products R&D LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Documented multiple myeloma (MM) diagnosis per IMWG criteria. 2. Measurable disease, defined as at least 1 of the following: 1. Serum M protein ≥0.5 grams per deciliter \[g/dL\] (≥5 g/L) on serum protein electrophoresis (SPEP). 2. Urine M protein ≥200 mg/24 hours on urine protein electrophoresis (UPEP). 3. Serum free light chain (FLC) assay with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal. 3. For participants in the Phase 1 Dose Escalation only: Must have received at least 3 prior lines of therapy, including at least 1 proteosome inhibitor (PI), 1 immunomodulatory imide drug (IMiD), and 1 anti-CD38 monoclonal antibody (mAb) drug; or who are triple refractory to a PI, an IMiD, and an anti-CD38 mAb drug, regardless of the number of prior line(s) or therapy. 4. For participants in Phase 2a Dose Finding only: 1. Received 1 to 3 prior line(s) of antimyeloma therapy. 2. Must be refractory to prior lenalidomide treatment. 3. Participants must be sensitive (nonrefractory) or naïve to prior anti-CD38 mAb treatment. 4. Documented progressive disease on or after the last regimen. 5. Participants must have PR or better to at least 1 line of prior therapy. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening.
Exclusion criteria
1. Prior exposure to modakafusp alfa. 2. Participant has polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, plasma cell leukemia, or lymphoplasmacytic lymphoma. 3. Participant has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE, Version 5 Grade ≤1 or baseline, except for alopecia. 4. Previous allogeneic stem cell transplant at any time or autologous stem cell transplant (ASCT) within 12 weeks of planned start of dosing. 5. Seropositive for hepatitis B, or known history of seropositivity for hepatitis C or of seropositivity for human immunodeficiency virus (HIV). 6. Participant has congestive heart failure (New York Heart Association Grade ≥II), cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant arrhythmia requiring therapy including anticoagulants, or clinically significant uncontrolled hypertension. 7. Participant has QT interval corrected by the Fridericia method \>480 milliseconds \[msec\] (Grade ≥2). 8. Participant has a chronic condition that will require the chronic use of systemic corticosteroids \>10 milligrams per day (mg/d) of prednisone or equivalent on top of any required corticosteroids for multiple myeloma (MM).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Dose Limiting Toxicities (DLT) | Phase 1: Cycle 1 (cycle length=28 days) | DLT was defined as any of the treatment-emergent adverse events (TEAEs) that occurred during Cycle 1 and were considered by the investigator to be at least possibly related to modakafusp alfa. Toxicity was evaluated according to national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 5.0. |
| Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Phase 1: Up to 15.9 months | 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 were evaluated as per the NCI CTCAE Version 5.0. |
| Phase 2a: Overall Response Rate (ORR) | Phase 2a: Up to 15.9 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Cmax: Single-Dose Maximum Observed Serum Concentration for Modakafusp Alfa | Phase 1: 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) | — |
| Phase 1: Tmax: Time to First Occurrence of Maximum Serum Concentration (Cmax) for Modakafusp Alfa | Phase 1: 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) | — |
| Phase 1: AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Modakafusp Alfa | Phase 1: 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) | — |
| Phase 1: AUClast: Area Under the Serum Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration | Phase 1: 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) | — |
| Phase 1: Apparent Serum Terminal Disposition Rate Constant for Modakafusp Alfa | Phase 1: 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) | — |
| Phase 1: Apparent Serum Terminal Disposition Phase Half-life for Modakafusp Alfa | Phase 1: 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) | — |
| Phase 1: Total Clearance After Intravenous Administration for Modakafusp Alfa | Phase 1: 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) | — |
| Phase 1: Volume of Distribution at Steady State After Intravenous (IV) Administration for Modakafusp Alfa | Phase 1: 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) | — |
| Phase 1: Cmax: Single-Dose Maximum Observed Serum Concentration for Daratumumab | Phase 1: 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) | — |
| Phase 1: Tmax: Time to First Occurrence of Maximum Serum Concentration (Cmax) for Daratumumab | Phase 1: 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) | — |
| Phase 1: Ctrough: Single-Dose and Multiple-dose Observed Concentration at the End of a Dosing Interval for Daratumumab | Phase 1: 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) | — |
| Phase 1: AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Daratumumab | Phase 1: 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) | — |
| Phase 1: AUClast: Area Under the Serum Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Daratumumab | Phase 1: 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) | — |
| Phase 1: Overall Response Rate (ORR) | Phase 1: Up to 15.9 months | 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. |
| Phase 1 and Phase 2a: Duration of Response (DOR) | Up to 15.9 months | 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. |
| Phase 1 and Phase 2a: Progression Free Survival (PFS) | Up to 15.9 months | 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. |
| Phase 1 and Phase 2a: Overall Survival (OS) | Up to 15.9 months | 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. |
| Phase 1 and Phase 2a: Number of Participants With Anti-drug Antibodies (ADA) | Up to 15.9 months | After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons and hence no participants were enrolled for Phase 2a. |
| Phase 1 and Phase 2a: Titer of Anti-drug Antibodies | Up to 15.9 months | — |
| Phase 1 and Phase 2a: Number of Participants With Neutralizing Antibodies (NAb) Against Study Drug | Up to 15.9 months | — |
| Phase 1 and Phase 2a: Rate of Measurable [Minimal] Residual Disease Negative (MRD[-]) Complete Response (CR) | Up to 15.9 months | 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. No participants had sCR or CR in Phase 1 thus the overall number of participants analyzed is zero. |
| Phase 1 and Phase 2a: Duration of Measurable [Minimal] Residual Disease (MRD) Negativity | Up to 15.9 months | 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. No participants had sCR or CR in Phase 1 thus the overall number of participants analyzed is zero. |
| Phase 2a: Clinical Benefit Rate (CBR) | Phase 2a: Up to 15.9 months | 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. |
| Phase 2a: Duration of Clinical Benefit (DCB) | Phase 2a: Up to 15.9 months | 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. |
| Phase 2a: Disease Control Rate (DCR) | Phase 2a: Up to 15.9 months | 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. |
| Phase 2a: Duration of Disease Control | Phase 2a: Up to 15.9 months | 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. |
| Phase 2a: Time to Progression (TTP) | Phase 2a: Up to 15.9 months | 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. |
| Phase 2a: Time to Response (TTR) | Phase 2a: Up to 15.9 months | 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. |
| Phase 2a: Time to Next Treatment (TTNT) | Phase 2a: Up to 15.9 months | 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. |
| Phase 2a: Number of Participants Reporting One or More TEAEs and Per Severity | Phase 2a: Up to 15.9 months | 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. |
Countries
Australia, Canada, China, France, South Korea, Spain, United States
Participant flow
Recruitment details
Participants took part in the study at 9 investigative sites globally from 23 January 2023 to 22 May 2024.
Pre-assignment details
Participants with multiple myeloma were enrolled in Phase 1 (Dose Escalation) to receive modakafusp alfa (80 milligrams \[mg\], 120 mg or 240 mg) + daratumumab. No participants were enrolled in Phase 2a (Dose Finding) as the study was terminated by the Sponsor due to strategic reasons.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab Participants received modakafusp alfa 80 mg, infusion, IV, Q4W with daratumumab 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression or up to 60 weeks. | 3 |
| Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab Participants received modakafusp alfa 120 mg, infusion, IV, Q4W with daratumumab 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression or up to 48 weeks. | 6 |
| Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab Participants received modakafusp alfa 240 mg, infusion, IV, Q4W with daratumumab 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression or up to 36 weeks. | 6 |
| Total | 15 |
Baseline characteristics
| Characteristic | Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab | Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab | Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab | Total |
|---|---|---|---|---|
| Age, Continuous | 59.2 years STANDARD_DEVIATION 12.02 | 71.7 years STANDARD_DEVIATION 18.34 | 63.7 years STANDARD_DEVIATION 11.64 | 63.5 years STANDARD_DEVIATION 13.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 4 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 1 / 6 | 2 / 6 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 1 / 6 | 2 / 6 |
Outcome results
Primary
Phase 1: Number of Participants Reporting One or More 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 were evaluated as per the NCI CTCAE Version 5.0.
Time frame: Phase 1: Up to 15.9 months
Population: The Safety Population included all participants who received at least 1 dose, even an incomplete dose, of any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 4 | 0 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 3 | 2 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 1 | 1 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 2 | 0 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 5 | 0 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 3 | 4 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 1 | 0 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 2 | 2 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 4 | 0 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 5 | 0 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 5 | 1 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 4 | 1 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 1 | 0 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 3 | 3 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab | Phase 1: Number of Participants Reporting One or More TEAEs and Per Severity | Grade 2 | 1 Participants |
Primary
Phase 1: Number of Participants With Dose Limiting Toxicities (DLT)
DLT was defined as any of the treatment-emergent adverse events (TEAEs) that occurred during Cycle 1 and were considered by the investigator to be at least possibly related to modakafusp alfa. Toxicity was evaluated according to national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 5.0.
Time frame: Phase 1: Cycle 1 (cycle length=28 days)
Population: The Dose Limiting Toxicity (DLT)-evaluable Population included all participants from the Phase 1 dose escalation portion who experienced a DLT in Cycle 1 in the treatment phase of the study or had completed the Cycle 1 dose of modakafusp alfa and at least 75% of the planned dose of daratumumab SC.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab | Phase 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab | Phase 1: Number of Participants With Dose Limiting Toxicities (DLT) | 0 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab | Phase 1: Number of Participants With Dose Limiting Toxicities (DLT) | 1 Participants |
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.
Time frame: Phase 2a: Up to 15.9 months
Population: After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons. Thus, no participants were enrolled for Phase 2a and no data was collected for this outcome measure due to study termination.
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. No participants had sCR or CR in Phase 1 thus the overall number of participants analyzed is zero.
Time frame: Up to 15.9 months
Population: Only participants who had a confirmed stringent CR (sCR) or complete response (CR) were to be analyzed for this outcome measure. After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons. Thus, no participants were enrolled for Phase 2a \& no data was collected for this outcome measure due to study termination.
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.
Time frame: Up to 15.9 months
Secondary
Phase 1 and Phase 2a: Number of Participants With Anti-drug Antibodies (ADA)
After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons and hence no participants were enrolled for Phase 2a.
Time frame: Up to 15.9 months
Population: Immunogenicity-evaluable Population included participants who received at least 1 dose of modakafusp alfa in combination with daratumumab SC (partial or complete) with a baseline assessment \& at least 1 postbaseline immunogenicity assessment. No data was collected for this outcome measure due to study termination. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab | Phase 1 and Phase 2a: Number of Participants With Anti-drug Antibodies (ADA) | 3 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab | Phase 1 and Phase 2a: Number of Participants With Anti-drug Antibodies (ADA) | 2 Participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab | Phase 1 and Phase 2a: Number of Participants With Anti-drug Antibodies (ADA) | 0 Participants |
Secondary
Phase 1 and Phase 2a: Number of Participants With Neutralizing Antibodies (NAb) Against Study Drug
Time frame: Up to 15.9 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.
Time frame: Up to 15.9 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.
Time frame: Up to 15.9 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. No participants had sCR or CR in Phase 1 thus the overall number of participants analyzed is zero.
Time frame: Up to 15.9 months
Population: Only participants who had a confirmed stringent CR (sCR) or complete response (CR) were to be analyzed for this outcome measure. After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons. Thus, no participants were enrolled for Phase 2a \& no data was collected for this outcome measure due to study termination.
Secondary
Phase 1 and Phase 2a: Titer of Anti-drug Antibodies
Time frame: Up to 15.9 months
Secondary
Phase 1: Apparent Serum Terminal Disposition Phase Half-life for Modakafusp Alfa
Time frame: Phase 1: 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
Time frame: Phase 1: 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: AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Daratumumab
Time frame: Phase 1: 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: AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Modakafusp Alfa
Time frame: Phase 1: 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
Time frame: Phase 1: 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
Time frame: Phase 1: 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
Time frame: Phase 1: 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 Modakafusp Alfa
Time frame: Phase 1: 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
Time frame: Phase 1: 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.
Time frame: Phase 1: Up to 15.9 months
Population: The Response-evaluable Population included all participants who received at least 1 dose, even an incomplete dose, of any study drug, have a disease assessment at screening (baseline evaluation), and at least 1 postbaseline disease assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab | Phase 1: Overall Response Rate (ORR) | 33.3 percentage of participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab | Phase 1: Overall Response Rate (ORR) | 66.7 percentage of participants |
| Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab | Phase 1: Overall Response Rate (ORR) | 50.0 percentage of participants |
Secondary
Phase 1: Tmax: Time to First Occurrence of Maximum Serum Concentration (Cmax) for Daratumumab
Time frame: Phase 1: 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
Time frame: Phase 1: 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
Time frame: Phase 1: 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 (IV) Administration for Modakafusp Alfa
Time frame: Phase 1: 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 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.
Time frame: Phase 2a: Up to 15.9 months
Population: After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons. Thus, no participants were enrolled for Phase 2a \& no data was collected for this outcome measure due to study termination.
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.
Time frame: Phase 2a: Up to 15.9 months
Population: After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons (no safety concerns). Thus, no participants were enrolled for Phase 2a \& no data was collected for this outcome measure due to study termination.
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.
Time frame: Phase 2a: Up to 15.9 months
Population: After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons (no safety concerns). Thus, no participants were enrolled for Phase 2a \& no data was collected for this outcome measure due to study termination.
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.
Time frame: Phase 2a: Up to 15.9 months
Population: After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons (no safety concerns). Thus, no participants were enrolled for Phase 2a \& no data was collected for this outcome measure due to study termination.
Secondary
Phase 2a: Number of Participants Reporting One or More 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.
Time frame: Phase 2a: Up to 15.9 months
Population: After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons (no safety concerns). Thus, no participants were enrolled for Phase 2a \& no data was collected for this outcome measure due to study termination.
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.
Time frame: Phase 2a: Up to 15.9 months
Population: After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons (no safety concerns). Thus, no participants were enrolled for Phase 2a \& no data was collected for this outcome measure due to study termination.
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.
Time frame: Phase 2a: Up to 15.9 months
Population: After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons (no safety concerns). Thus, no participants were enrolled for Phase 2a \& no data was collected for this outcome measure due to study termination.
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.
Time frame: Phase 2a: Up to 15.9 months
Population: After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons (no safety concerns). Thus, no participants were enrolled for Phase 2a \& no data was collected for this outcome measure due to study termination.