Multiple Myeloma
Conditions
Keywords
Drug Therapy
Brief summary
The main aims of this study are to test for any side effects from modakafusp alfa in combination therapy and to determine the recommended dose of combination therapy with modakafusp alfa. 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. Participants will be given modakafusp alfa through a vein.
Detailed description
The drug being tested in this study is called modakafusp alfa (TAK-573). The study will evaluate the safety, tolerability and determine the recommended dose of modakafusp alfa in combination with lenalidomide in participants with multiple myeloma (MM), or in combination with pomalidomide, bortezomib, carfilzomib, or daratumumab in participants with relapsed/refractory multiple myeloma (RRMM). The study consists of 3 Groups: Group 1: MM Maintenance Therapy, Group 2: RRMM Doublets, Group 3: RRMM Triplets. The study will enroll approximately 18 participants in Group 1, 66 in Group 2, and 36 in Group 3. Participants will be assigned to one of the following treatment groups as given below: * Group 1 (MM Maintenance) Arm 1: Modakafusp alfa + Lenalidomide * Group 2 (RRMM Doublets) Arm 2: Modakafusp alfa + Pomalidomide * Group 2 (RRMM Doublets) Arm 3: Modakafusp alfa + Bortezomib * Group 2 (RRMM Doublets) Arm 4: Modakafusp alfa + Carfilzomib * Group 3 RRMM Triplets) Arm A: Modakafusp alfa + Pomalidomide + Bortezomib * Group 3 (RRMM Triplets) Arm D: Modakafusp alfa + Daratumumab + Pomalidomide Group 2 Arm 4 is closed for enrollment. The study will be conducted worldwide. The maximum treatment duration in this study for Group 1 is until disease progression or unacceptable toxicity, or up to 2 years for minimal/measurable residual disease (MRD) negative \[-\] participants, whichever occurs first. The maximum treatment duration in this study for Group 2 and Group 3 is until disease progression, unacceptable toxicity or until any other discontinuation criterion is met, whichever occurs first. Overall time to participate in the study is approximately up to 5 years.
Interventions
DRUGModakafusp alfa
Modakafusp alfa intravenous infusion.
DRUGLenalidomide
Lenalidomide capsules orally.
DRUGBortezomib
Bortezomib injection subcutaneously.
DRUGCarfilzomib
Carfilzomib intravenous infusion.
DRUGDaratumumab
Daratumumab injection subcutaneously.
DRUGPomalidomide
Pomalidomide capsules orally.
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. Group 1 (MM maintenance: modakafusp alfa/lenalidomide) only must have: 1. MM based on standard IMWG diagnostic criteria. 2. Undergone autologous stem cell transplantation (ASCT) for the treatment of MM within 12 months of the start of induction therapy and completed ASCT within 180 days before enrollment- (regardless of the lines of treatment).Consolidation cycles are allowed. Tandem transplant is allowed. 3. Not started lenalidomide maintenance before enrollment. Time to initiation of maintenance therapy: participants may start maintenance therapy as early as 60 days after transplantation and up to 180 days after transplantation or consolidation. 4. MRD positive ( after ASCT (MRD assessed at a threshold of 10\^-5 by local standard-of-care (SOC) methods or central assessment, if a prior local MRD assessment had not been performed). 5. No prior progression after initial therapy (at any time before starting maintenance). Participants whose induction therapy was changed due to suboptimal response or toxicity will be eligible if they do not meet criteria for progression. In addition, no more than 2 regimens will be allowed before ASCT, excluding dexamethasone alone. 6. No prior allogeneic hematopoietic stem cell transplant or solid organ transplant. 7. Recovered to Grade less than or equal to (\<=) 1 ASCT-related toxicities from the reversible effects of ASCT (except for alopecia and amenorrhea). MM based on standard IMWG diagnostic criteria. 2. Groups 2 and 3 (RRMM doublets and RRMM triplets) must have: 1. Measurable disease, defined as at least 1 of the following: * Serum M-protein \>=0.5 g/dL (\>=5 g/L) on serum protein electrophoresis (SPEP). * Urine M-protein \>=200 mg/24 hours on urine protein electrophoresis (UPEP). * Serum free light chain (FLC) assay result with an involved FLC level \>=10 mg/dL (\>=100 mg/L), provided the serum FLC ratio is abnormal (per IMWG criteria). 2. A confirmed diagnosis of MM according to International Myeloma Working Group (IMWG) criteria with documented disease progression in need of additional therapy as determined by the investigator. 3. For Group 2 RRMM doublet arms only: Participants who have received at least 3 prior lines of antimyeloma therapy, including at least 1 proteosome inhibitor (PI), 1 immunomodulatory drug (IMiD) and 1 anti-CD38 monoclonal antibody (mAb) drug, or who are triple refractory to a PI, and IMiD, and an anti-CD38 mAb drug regardless of the number of prior line(s) of therapy. d. For Group 3 RRMM triplet arms only: Participants who have received 1 to 3 prior lines of antimyeloma therapy including at least 1 PI and, 1 IMiD, and who are not refractory to the combination partners. e) For anti-CD38 arms, forced expiratory volume in 1second (FEV1) \>=50% predicted by pulmonary function testing. 3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening 4. Has adequate organ function at screening as determined by the laboratory values required for enrollment: Absolute neutrophil count (ANC) \>=1000 per cubic millimeter (/mm\^3) (or \>=1\*10\^9/L); Platelets \>=75,000/mm\^3 (\>=75\*10\^9/L); Hemoglobin \>=8.0 g/dL; estimated creatinine clearance \>=30 mL/min (Cockcroft-Gault formula); Total serum bilirubin \<=2.0\*Upper limit of normal (ULN); an exception for participants with Gilbert's syndrome may be granted after discussion with the sponsor; Liver transaminases (alanine aminotransferase \[ALT\])/aspartate aminotransferase \[AST\]) \<=3.0\*ULN. 5. Has recovered from adverse reactions to prior myeloma treatment or procedures (example, chemotherapy, immunotherapy, radiation therapy) to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Grade \<=1 or baseline treatment or have the toxicity established as sequela, except for sensory or motor neuropathy, which should have recovered to Grade \<=2 or baseline; ; (Grade 1 for the bortezomib arm).
Exclusion criteria
1. Currently participating in another MM interventional study, including other clinical trials with investigational agents (including investigational vaccines or investigational medical device for disease under study) throughout the duration of this study. 2. Received previous treatment with modakafusp alfa. 3. Has a diagnosis of primary amyloidosis, Waldenström disease, monoclonal gammopathy of undetermined significance or smoldering MM per IMWG criteria or standard diagnostic criteria, plasma cell leukemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), lymphoplasmacytic lymphoma. 4. Has been diagnosed with another 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 and that in the opinion of the local investigator, with concurrence with the principal investigator, is considered cured with minimal risk of recurrence within 3 years. 5. Has evidence of central nervous system (CNS) involvement and/or meningeal involvement due to MM exhibited during screening. 6. Has a known severe allergic or anaphylactic reactions to human recombinant proteins or excipients used in the modakafusp alfa formulation or to the study combination agents, the study medications, their analogs, or excipients in the various formulations of any agent per the prescribing information. 7. Is 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 and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) and, a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR. 8. Has a known history of seropositivity for HIV. 9. Has a known history of seropositivity for hepatitis C (anti-hepatitis C virus \[HCV\] antibody positive or anti-hepatitis C virus-RNA quantitation positive). Exception: Participants with a sustained virologic response with undetectable HCV RNA level at least 12 weeks after completion of antiviral therapy. 10. For bortezomib arms: participants received a strong cytochromes P450 (CYP3A4) inducer within 5 half-lives prior to randomization. 11. The participant has a chronic condition requiring the use of systemic corticosteroids \>10 mg/dL of prednisone or equivalent, in addition to any required corticosteroids for the treatment of MM. 12. Has a QTcF (QT interval corrected with Fridericia correction method \>480 millisecond (ms) (Grade \>=2).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLTs) | Cycle 1 (Cycle length is 28 days) | DLT was defined by national cancer institute common terminology criteria for adverse events (NCI CTCAE) version 5.0: Grade 5 AE; Hematologic toxicity: Nonfebrile Grade 4 neutropenia lasting more than 7 consecutive days/Grade greater than or equal to (\>=) 3 febrile neutropenia; Grade 4 thrombocytopenia lasting more than 14 consecutive days, Grade 3 thrombocytopenia with clinically significant bleeding; any other Grade 4 with exceptions; Nonhematologic Grade 3 or higher toxicities unrelated to the underlying disease with exceptions. |
| Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) | Up to 16.7 months | An adverse event (AE) is defined as any untoward medical occurrence in a participants administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to 16.7 months | PFS was defined as the time from the date on which the first dose of study drug is administered to the date of first documentation of confirmed progression of disease (PD) or death due to any cause, whichever occurs first. PD was determined by International Myeloma Working Group (IMWG) criteria. PD: increase of ≥25 percent (%) from lowest response value in any one or more of the following: serum M-component increase ≥0.5 gram per deciliter (g/dL) or urine M-component increase ≥200 milligram (mg)/24-hour; difference between involved and uninvolved free light chains (FLC) levels increase must be greater than (\>) 10 milligram per deciliter (mg/dL); bone marrow plasma cell ≥10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder. |
| Overall Response Rate (ORR) | Up to 16.7 months | ORR: percentage of participants achieving confirmed partial response rate(PR)or better(stringent complete response\[sCR\]+complete response\[CR\]+very good partial response\[VGPR\]+PR)during study as defined by IMWG uniform response criteria and as determined by investigator.PR:\>=50%reduction of serum M-protein and\>=90% reduction in urine M-protein or less than(\<)200mg/24 hour, or\>=50%decrease in uninvolved FLC or \>=50% reduction in plasma cells. At baseline,a \>=50% decrease in size of soft tissue plasmacytomas was required. Percentages were rounded off to nearest single decimal place. Due to early termination of study no participants were enrolled in Group 2 Arm 4: modakafusp alfa+bortezomib and Group 3 arms, thus they are not presented here. Also, no participants in Group 1 fulfilled criteria for Response-Evaluable Analysis Set, hence are not presented here. Given limited number of participants and low confidence interval as a consequence, those response rate provides limited information. |
| Duration of Response (DOR) | Up to 16.7 months | DOR was defined as the time from the date of first documentation of confirmed PR or better (sCR+ CR+ VGPR+ PR) to the date of first documentation of PD or death due to any cause. PR: \>=50% reduction of serum M-protein and \>=90% reduction in urine M-protein or \<200 mg/24 hour, or \>=50% decrease in uninvolved FLC or \>=50% reduction in plasma cells. At baseline, a \>=50% decrease in size of soft tissue plasmacytomas is required. PD: increase of \>=25% from lowest response value in any one or more of the following: serum M-component increase \>=0.5 g/dL or urine M-component increase \>=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be \>10 mg/dL; bone marrow plasma cell \>=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder. |
| Groups 2 and 3: Overall Survival (OS) | Up to 16.7 months | OS was defined as the time from the first dose of administration to the date of death, due to any cause. Participants without documentation of death at the time of analysis were censored at the date last known to be alive. |
| Groups 2 and 3: Time to Progression (TTP) | Up to 16.7 months | TTP was 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. PD: increase of \>=25% from lowest response value in any one or more of the following: serum M-component increase \>=0.5 g/dL or urine M-component increase \>=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be \>10 mg/dL; bone marrow plasma cell \>=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder. |
| Groups 2 and 3: Time to Next Treatment (TTNT) | Up to 16.7 months | TTNT was defined as the time from the date of first dose administration to the date of the first dose initiation of the next line of antineoplastic therapy, for any reason. |
| Groups 2 and 3: Disease Control Rate (DCR) | Up to 16.7 months | DCR was defined as the percentage of participants who achieved a stable disease (SD) or better during the study based on the investigator's disease assessment as defined by IMWG uniform response criteria. SD was defined as no known evidence of progressive disease or new bone lesions. Percentages were rounded off to the nearest single decimal place. |
| Groups 2 and 3: Event-free Survival (EFS) | Up to 16.7 months | EFS was defined as the time from the date on which the first dose of study drug is administered to the date of the first documentation of an event that may include confirmed PD, discontinuation of a treatment for an AE (related or not related), or death due to any cause, whichever occurs first. PD was determined by IMWG criteria. PD: increase of \>=25 % from lowest response value in any one or more of the following: serum M-component increase \>=0.5 g/dL or urine M-component increase \>=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be \> 10 mg/dL; bone marrow plasma cell \>=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder. |
| Groups 2 and 3: Time to Response (TTR) | Up to 16.7 months | TTR was defined as the time from the date of the first dose administration to the date of the first documentation of objective confirmed response as defined by IMWG criteria. |
| Group 1: Percentage of Participants With MRD Negativity Status at a Threshold of 10^-5 | At 6 months, 1 year, and 2 years after the start of treatment | Rate of MRD negativity at a sensitivity of 10\^-5 was defined as the percentage of participants who achieved MRD negative status in the MRD-evaluable analysis set. |
| Groups 2 and 3: Percentage of Participants With MRD Negativity CR Status at a Threshold of 10^-5 in Participants Achieving CR Assessed by the Investigator | Up to 2 years after CR confirmation | Rate of MRD negativity CR status a sensitivity of 10\^-5 was defined as the percentage of participants who have achieved MRD negative CR status in participants achieving 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. |
| Duration of MRD Negativity Status at a Threshold of 10^-5 in Participants Achieving MRD Negativity | Up to 2 years after treatment | Duration of MRD negativity (10\^-5) was defined as the time from the date of first documentation of MRD\[-\] to the first documentation of MRD positivity or confirmed PD or death due to any cause, whichever occurred first. PD: increase of \>=25% from lowest response value in any one or more of the following: serum M-component increase \>=0.5 g/dL or urine M-component increase \>=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be \>10 mg/dL; bone marrow plasma cell \>=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder. |
| Group 2 and 3: Percentage of Participants With MRD Negativity Status at a Threshold of 10^-5 | Up to 16.7 months | Rate of MRD negativity at a sensitivity of 10\^-5 was defined as the percentage of participants who have achieved MRD negative status. |
| Groups 2 and 3: Duration of MRD Negativity Status at a Sensitivity Threshold of 10^-5 in Participants Achieving MRD Negativity | Up to 16.7 months | Duration of MRD negativity (10\^-5) was defined as the time from the date of first documentation of MRD\[-\] to the first documentation of MRD positivity or confirmed PD or death due to any cause, whichever occurred first. PD: increase of \>=25% from lowest response value in any one or more of the following: serum M-component increase \>=0.5 g/dL or urine M-component increase \>=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be \>10 mg/dL; bone marrow plasma cell \>=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder. |
| Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibody (NAb) | Up to 16.7 months | — |
Countries
Belgium, Israel, Spain, United States
Participant flow
Recruitment details
Participants took part in the study at various investigative sites globally from 12 January 2023 to 04 June 2024.
Pre-assignment details
Participants with a diagnosis of multiple myeloma (MM) were enrolled in this study. Participants with newly diagnosed MM (NDMM) received modakafusp alfa in combination with lenalidomide and participants with relapsed/refractory MM (RRMM) received modakafusp alfa in combination with pomalidomide or carfilzomib. Due to early termination of the study no participants were enrolled in Group 2 Arm 4: modakafusp alfa + bortezomib and Group 3 arms.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg Participants received 80 mg modakafusp alfa, infusion IV, once on Day 1, Q4W, in combination with 10 mg lenalidomide capsules orally once daily continuously on Days 1 to 28, in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or to a maximum of 2 years for MRD \[-\] negative participants, whichever occurred first. | 3 |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg Participants received 80 mg modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with 2 mg pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion was met, whichever occurred first. | 4 |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg Participants received 80 mg modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with 4 mg pomalidomide capsules orally once daily on Days 1 to 21 in a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion was met, whichever occurred first. | 4 |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Carfilzomib 20/70 mg/m^2 Participants received 80 mg modakafusp alfa, infusion IV, once on Day 1, Q4W in combination with 20/70 mg/m\^2 carfilzomib IV, on Day 1, 8 and 15 of a 28-day (4-week) treatment cycle until disease progression, unacceptable toxicity, or until any other discontinuation criterion was met, whichever occurred first. | 3 |
| Total | 14 |
Baseline characteristics
| Characteristic | Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg | Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Carfilzomib 20/70 mg/m^2 | Total | Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg | Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg |
|---|---|---|---|---|---|
| Age, Continuous | 71.3 years STANDARD_DEVIATION 2.63 | 57.3 years STANDARD_DEVIATION 12.06 | 64.4 years STANDARD_DEVIATION 11.47 | 62.3 years STANDARD_DEVIATION 18.5 | 64.3 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 3 Participants | 11 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 5 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 7 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 4 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 10 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 4 | 2 / 4 | 1 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 4 | 4 / 4 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 1 / 4 | 1 / 4 | 3 / 3 |
Outcome results
Primary
Number of Participants With Dose-limiting Toxicities (DLTs)
DLT was defined by national cancer institute common terminology criteria for adverse events (NCI CTCAE) version 5.0: Grade 5 AE; Hematologic toxicity: Nonfebrile Grade 4 neutropenia lasting more than 7 consecutive days/Grade greater than or equal to (\>=) 3 febrile neutropenia; Grade 4 thrombocytopenia lasting more than 14 consecutive days, Grade 3 thrombocytopenia with clinically significant bleeding; any other Grade 4 with exceptions; Nonhematologic Grade 3 or higher toxicities unrelated to the underlying disease with exceptions.
Time frame: Cycle 1 (Cycle length is 28 days)
Population: The DLT-evaluable Analysis Set included participants who experienced a DLT in Cycle 1 in the treatment phase of the study or completed Cycle 1 procedures and received a full Cycle 1 dose of modakafusp alfa and at least 75% of the planned dose of the combination partner. Due to early termination of the study no participants were enrolled in Group 2 Arm 4: modakafusp alfa + bortezomib and Group 3 arms, thus they are not presented here.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg | Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg | Number of Participants With Dose-limiting Toxicities (DLTs) | 1 Participants |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg | Number of Participants With Dose-limiting Toxicities (DLTs) | 1 Participants |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Carfilzomib 20/70 mg/m^2 | Number of Participants With Dose-limiting Toxicities (DLTs) | 2 Participants |
Primary
Number of Participants With 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A TEAE was 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.
Time frame: Up to 16.7 months
Population: The SAS included all participants who had received at least 1 dose, even if incomplete, of any study drug. Due to early termination of the study no participants were enrolled in Group 2 Arm 4: modakafusp alfa + bortezomib and Group 3 arms, thus they are not presented here.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Carfilzomib 20/70 mg/m^2 | Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
Secondary
Duration of MRD Negativity Status at a Threshold of 10^-5 in Participants Achieving MRD Negativity
Duration of MRD negativity (10\^-5) was defined as the time from the date of first documentation of MRD\[-\] to the first documentation of MRD positivity or confirmed PD or death due to any cause, whichever occurred first. PD: increase of \>=25% from lowest response value in any one or more of the following: serum M-component increase \>=0.5 g/dL or urine M-component increase \>=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be \>10 mg/dL; bone marrow plasma cell \>=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.
Time frame: Up to 2 years after treatment
Population: MRD data was not collected as no participant achieved the criteria for MRD-evaluable analysis set (i.e., achieving a Complete Response).
Secondary
Duration of Response (DOR)
DOR was defined as the time from the date of first documentation of confirmed PR or better (sCR+ CR+ VGPR+ PR) to the date of first documentation of PD or death due to any cause. PR: \>=50% reduction of serum M-protein and \>=90% reduction in urine M-protein or \<200 mg/24 hour, or \>=50% decrease in uninvolved FLC or \>=50% reduction in plasma cells. At baseline, a \>=50% decrease in size of soft tissue plasmacytomas is required. PD: increase of \>=25% from lowest response value in any one or more of the following: serum M-component increase \>=0.5 g/dL or urine M-component increase \>=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be \>10 mg/dL; bone marrow plasma cell \>=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.
Time frame: Up to 16.7 months
Secondary
Group 1: Percentage of Participants With MRD Negativity Status at a Threshold of 10^-5
Rate of MRD negativity at a sensitivity of 10\^-5 was defined as the percentage of participants who achieved MRD negative status in the MRD-evaluable analysis set.
Time frame: At 6 months, 1 year, and 2 years after the start of treatment
Population: MRD data was not collected as no participant achieved the criteria for MRD-evaluable analysis set (i.e., being on study at 6 months).
Secondary
Group 2 and 3: Percentage of Participants With MRD Negativity Status at a Threshold of 10^-5
Rate of MRD negativity at a sensitivity of 10\^-5 was defined as the percentage of participants who have achieved MRD negative status.
Time frame: Up to 16.7 months
Population: MRD data was not collected as no participant achieved the criteria for MRD-evaluable analysis set (i.e., achieving a Complete Response).
Secondary
Groups 2 and 3: Disease Control Rate (DCR)
DCR was defined as the percentage of participants who achieved a stable disease (SD) or better during the study based on the investigator's disease assessment as defined by IMWG uniform response criteria. SD was defined as no known evidence of progressive disease or new bone lesions. Percentages were rounded off to the nearest single decimal place.
Time frame: Up to 16.7 months
Population: The Response-Evaluable Analysis Set was a subset of SAS including participants with measurable disease at baseline and at least 1 post-baseline efficacy evaluation. Due to early termination of the study no participants were enrolled in Group 2 Arm 4: modakafusp alfa + bortezomib and Group 3 arms, thus they are not presented here. Also, no participants in Group 1 fulfilled the criteria for the Response-Evaluable Analysis Set and hence are not presented here.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg | Groups 2 and 3: Disease Control Rate (DCR) | 75.0 percentage of participants |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg | Groups 2 and 3: Disease Control Rate (DCR) | 50.0 percentage of participants |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg | Groups 2 and 3: Disease Control Rate (DCR) | 66.7 percentage of participants |
Secondary
Groups 2 and 3: Duration of MRD Negativity Status at a Sensitivity Threshold of 10^-5 in Participants Achieving MRD Negativity
Duration of MRD negativity (10\^-5) was defined as the time from the date of first documentation of MRD\[-\] to the first documentation of MRD positivity or confirmed PD or death due to any cause, whichever occurred first. PD: increase of \>=25% from lowest response value in any one or more of the following: serum M-component increase \>=0.5 g/dL or urine M-component increase \>=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be \>10 mg/dL; bone marrow plasma cell \>=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.
Time frame: Up to 16.7 months
Population: MRD data was not collected as no participant achieved the criteria for MRD-evaluable analysis set (i.e., achieving a Complete Response).
Secondary
Groups 2 and 3: Event-free Survival (EFS)
EFS was defined as the time from the date on which the first dose of study drug is administered to the date of the first documentation of an event that may include confirmed PD, discontinuation of a treatment for an AE (related or not related), or death due to any cause, whichever occurs first. PD was determined by IMWG criteria. PD: increase of \>=25 % from lowest response value in any one or more of the following: serum M-component increase \>=0.5 g/dL or urine M-component increase \>=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be \> 10 mg/dL; bone marrow plasma cell \>=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.
Time frame: Up to 16.7 months
Secondary
Groups 2 and 3: Overall Survival (OS)
OS was defined as the time from the first dose of administration to the date of death, due to any cause. Participants without documentation of death at the time of analysis were censored at the date last known to be alive.
Time frame: Up to 16.7 months
Secondary
Groups 2 and 3: Percentage of Participants With MRD Negativity CR Status at a Threshold of 10^-5 in Participants Achieving CR Assessed by the Investigator
Rate of MRD negativity CR status a sensitivity of 10\^-5 was defined as the percentage of participants who have achieved MRD negative CR status in participants achieving 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.
Time frame: Up to 2 years after CR confirmation
Population: MRD data was not collected as no participant achieved the criteria for MRD-evaluable analysis set (i.e., achieving a Complete Response).
Secondary
Groups 2 and 3: Time to Next Treatment (TTNT)
TTNT was defined as the time from the date of first dose administration to the date of the first dose initiation of the next line of antineoplastic therapy, for any reason.
Time frame: Up to 16.7 months
Secondary
Groups 2 and 3: Time to Progression (TTP)
TTP was 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. PD: increase of \>=25% from lowest response value in any one or more of the following: serum M-component increase \>=0.5 g/dL or urine M-component increase \>=200 mg/24-hour; difference between involved and uninvolved FLC levels increase must be \>10 mg/dL; bone marrow plasma cell \>=10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.
Time frame: Up to 16.7 months
Secondary
Groups 2 and 3: Time to Response (TTR)
TTR was defined as the time from the date of the first dose administration to the date of the first documentation of objective confirmed response as defined by IMWG criteria.
Time frame: Up to 16.7 months
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADA) and Neutralizing Antibody (NAb)
Time frame: Up to 16.7 months
Secondary
Overall Response Rate (ORR)
ORR: percentage of participants achieving confirmed partial response rate(PR)or better(stringent complete response\[sCR\]+complete response\[CR\]+very good partial response\[VGPR\]+PR)during study as defined by IMWG uniform response criteria and as determined by investigator.PR:\>=50%reduction of serum M-protein and\>=90% reduction in urine M-protein or less than(\<)200mg/24 hour, or\>=50%decrease in uninvolved FLC or \>=50% reduction in plasma cells. At baseline,a \>=50% decrease in size of soft tissue plasmacytomas was required. Percentages were rounded off to nearest single decimal place. Due to early termination of study no participants were enrolled in Group 2 Arm 4: modakafusp alfa+bortezomib and Group 3 arms, thus they are not presented here. Also, no participants in Group 1 fulfilled criteria for Response-Evaluable Analysis Set, hence are not presented here. Given limited number of participants and low confidence interval as a consequence, those response rate provides limited information.
Time frame: Up to 16.7 months
Population: Response-Evaluable Analysis Set was a subset of SAS including participants with measurable disease at baseline \& at least 1 post-baseline efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (NDMM): Modakafusp Alfa 80 mg + Lenalidomide 10 mg | Overall Response Rate (ORR) | 0 percentage of participants |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 2 mg | Overall Response Rate (ORR) | 50 percentage of participants |
| Group 2 (RRMM Doublets): Modakafusp Alfa 80 mg + Pomalidomide 4 mg | Overall Response Rate (ORR) | 33.3 percentage of participants |
Secondary
Progression Free Survival (PFS)
PFS was defined as the time from the date on which the first dose of study drug is administered to the date of first documentation of confirmed progression of disease (PD) or death due to any cause, whichever occurs first. PD was determined by International Myeloma Working Group (IMWG) criteria. PD: increase of ≥25 percent (%) from lowest response value in any one or more of the following: serum M-component increase ≥0.5 gram per deciliter (g/dL) or urine M-component increase ≥200 milligram (mg)/24-hour; difference between involved and uninvolved free light chains (FLC) levels increase must be greater than (\>) 10 milligram per deciliter (mg/dL); bone marrow plasma cell ≥10%; definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.
Time frame: Up to 16.7 months