A Study of Ramantamig Plus Daratumumab Versus Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (DVRd) or Daratumumab, Lenalidomide, and Dexamethasone (DRd) in Participants With NDMM For Whom Stem Cell Transplant is Not Planned

Phase 3Not Yet RecruitingNCT07665450

Janssen Research & Development, LLC1,000 enrolled

Overview

The main purpose of this study is to see how well a new treatment ramantamig-D works compared to standard treatments that is either DVRd or DRd on progression-free survival (PFS; time until a participant's disease worsens) and 12-month minimal residue disease (MRD)-negative complete response (CR) rate (percentage of participants in whom cancer cells are not detected) in participants with newly diagnosed multiple myeloma (NDMM; an initial stage of blood cancer that forms in a type of white blood cells \[WBCs\] called plasma cells) for whom stem cell transplant is not planned as initial therapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,000

Conditions

Multiple Myeloma

Interventions

Ramantamig

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: * Documented diagnosis of multiple myeloma (MM) according to the IMWG diagnostic criteria * Not considered for high-dose chemotherapy with autologous stem cell transplantation (ASCT) due to: i. ineligible due to advanced age; or ii. ineligible due to presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT; or iii. deferral of high-dose chemotherapy with ASCT as initial treatment * Have an eastern cooperative oncology status (ECOG) performance status of 0 to 2 * Must sign an informed consent form (ICF) * Measurable disease at screening as assessed by central laboratory as defined in the protocol Exclusion criteria: * Myeloma Frailty Score of greater than or equal to (\>=) 2 with the exception of participants who have a score of 2 based on age alone * Suspected or known allergies, hypersensitivity, intolerance or other contraindications to any trial intervention or its excipients * Had major surgery (for example, requiring general anesthesia) or had significant traumatic injury within 2 weeks prior to first dose or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the trial * Known active or prior CNS involvement or exhibits clinical signs of meningeal involvement of MM * Received any prior therapy(ies) for treatment of MM or smoldering myeloma, with the exception of emergency use of a short course of corticosteroids

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

PFS is defined as the time from treatment assignment (that is, randomization in the trial) to confirmed progression of disease (PD) or death, whichever occurs first.

Time frame: Up to approximately 62 months

Percentage of Participants Achieving 12-Month Minimal Residual Disease (MRD)-Negative Complete Response CR

12-month MRD-negative CR rate is defined as achieving MRD-negative status at the analysis time window of 12 months (+/-3 months), as determined by next-generation sequencing (NGS) with sensitivity of 10\^-5, prior to PD or subsequent antimyeloma therapy (including ASCT). Additionally, CR or better must be achieved any time from randomization up to and including 12+3 months, according to international myeloma working group (IMWG) criteria.

Time frame: Up to 12 months

Secondary Outcomes

Overall Survival (OS)

OS is defined as time from treatment assignment (that is, randomization in the trial) to date of death due to any cause.

Time frame: Up to approximately 100 months

Percentage of Participants Achieving 24-Month Sustained MRD-Negative CR

24-month sustained MRD-negative CR is defined as achieving confirmed CR or better while sustaining MRD-negative status for at least 24 months without any examination showing MRD positive status or PD in between.

Time frame: Up to 5 years

Percentage of Participants with Very Good Partial Response (VGPR) or Better

Percentage of participants achieving VGPR, CR, or stringent complete response (sCR) prior to subsequent antimyeloma therapy in accordance with IMWG criteria during or after the trial intervention will be reported.

Time frame: Up to 5 years

Percentage of Participants with CR or Better

Percentage of participants achieving CR, or sCR prior to subsequent antimyeloma therapy in accordance with IMWG criteria during or after the trial intervention will be reported.

Time frame: Up to 5 years

Percentage of Participants with Overall Response

Percentage of participants achieving PR or better prior to subsequent antimyeloma therapy in accordance with IMWG criteria during or after the trial intervention will be reported.

Time frame: Up to 5 years

Percentage of Participants with Overall MRD-Negative CR

Percentage of participants who achieve MRD-negative status, as determined by NGS at any time point after randomization and prior to PD or subsequent antimyeloma therapy and who achieve CR or better will be reported.

Time frame: Up to 5 years

Percentage of Participants with 12-Month Sustained MRD-Negative CR

Percentage of participants with confirmed CR or better who sustain MRD-negative status, as determined by NGS, for at least 12 months without any examination showing MRD-positive status or PD in between will be reported.

Time frame: Up to 5 years

Progression Free Survival After Subsequent Therapy (PFS2)

PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as PD as assessed by investigator on the first subsequent line of antimyeloma therapy, or death from any cause, whichever occurs first.

Time frame: Up to approximately 100 months

Number of Participants with Adverse Events (AEs)

An AE is any untoward medical occurrence in a clinical trial participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention.

Time frame: Up to approximately 100 months

Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Scale Score

The MySIm-Q is a disease-specific PRO assessment complementary to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30). It includes 17 items with recall period of "7 days" and responses are reported on a 5-point verbal rating scale. Item responses are scored from 0 to 4. Higher scores indicate greater severity/impact.