A Study to Assess A Change in Disease Activity and Adverse Events of Intravenous Etentamig and Daratumumab (Etentamig+D) Compared to Daratumumab, Lenalidomide, and Dexamethasone (DRd) in Adult Participants With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Clinical activity is defined as change in response rates [Overall Response Rate (ORR), Complete Response (CR) or Better, Very Good Partial Response (VGPR), Partial Response (PR)] as determined International Myeloma Working Group (IMWG (2016).

MRDnegCR rate, is defined as the percentage of participants who have achieved stringent complete response (sCR) or CR as assessed by independent review committee (IRC) and have negative MRD defined at 10^-5 threshold as assessed by next generation sequencing (NGS).

PFS is defined as the duration from the date of randomization to the date of confirmed disease progression (PD) determined by IRC per IMWG (2016) response criteria, or death, whichever occurs first.

MRDnegCR rate, is defined as the percentage of participants who have achieved sCR or CR and have negative MRD defined at 10^-5 threshold as assessed by NGS.

PFS is defined as the duration from the date of randomization to the date of confirmed disease progression (PD) determined by IRC per IMWG (2016) response criteria, or death, whichever occurs first.

The rate of sustained MRD-negativity is defined as the percentage of participants with maintenance of MRD negativity status in bone marrow confirmed >=12 months apart prior to initiation of new anti-MM therapy.

Area under the plasma concentration-time curve (AUC).

OS is defined as the duration from the date of randomization to the date of the participant's death.

Incidence, severity, seriousness, and causality of treatment-emergent adverse events (TEAEs)

Maximum observed serum concentration (Cmax).

Time to Cmax.

Positive ADAs.

Negative ADAs.

Neutralizing anti-drug antibodies (NAbs).

OS is defined as the duration from the date of randomization to the date of the participant's death.

The rate of sustained MRD-negativity is defined as the percentage of participants with maintenance of MRD negativity status in bone marrow confirmed >=12 months apart prior to initiation of new anti-MM therapy.

The rate of >= CR is defined as the percentage of participants who achieve a sCR or CR determined by IMWG (2016) response criteria, per IRC assessment, prior to the initiation of new anti-myeloma therapy.

The rate of >= VGPR is defined as the percentage of participants who achieve a VGPR or better determined by IMWG (2016) response criteria, per IRC assessment, prior to the initiation of new anti-myeloma therapy.

ORR is defined as percentage of participants with a response of PR or better per IMWG criteria.

TTR is defined as the number of months from the date of first dose to the date of best overall response of CR or PR ('responders') determined by IMWG criteria as assessed by investigator.

DOR is defined as the number of days from the day the response criteria are met to the date that disease progression.

Time to progression is defined as the number of days from the date of study drug start to the date of the first documented disease progression or relapse.

EFS will be measured as the number of days between the initiation of the studied line of therapy and disease progression, or refractory disease, or death.

PFS2 is defined as the duration from the date of randomization to the date of confirmed disease progression or death on the next line of therapy.

Incidence, severity, seriousness, and causality of TEAEs

The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Subjects rate items on a 4- point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).

The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Subjects rate items on a 4- point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).

The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Subjects rate items on a 4- point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).

PRO-CTCAE includes 124 items representing 78 symptomatic toxicities drawn from the CTCAE. PRO-CTCAE items evaluate the symptom attributes of frequency, severity, interference, amount, presence/absence. All questions employ a 7-day recall period and are scored from 0 to 4 (or 0/1 for absent/present).

The FACT-G GP5 Item is a part of the FACT-G which is a 27-item questionnaire that measures four domains of health-related quality of life (HRQOL) in cancer patients: physical, social, emotional and functional well-being. The FACT-G GP5 item ("I am bothered by side effects of treatment") is used to assess overall treatment tolerability in patients by assessing the overall side effect impact on patients. This item is rated on a 5-point Likert scale from "not at all" to "very much.".

The PGIS scale asks the patient to assess their overall QoL, as well as difficulty of doing physical activities due to MM over the past 7 days. Each item employs a 5-point Likert scale from "not at all" to "very much."

The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems.