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

NCT07665450 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 79635322MMY3004
• Study Type: interventional
• Target: 1,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 12 months

Secondary Outcomes (15)

• Overall Survival (OS)

  Up to approximately 100 months

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

  Up to 5 years

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

  Up to 5 years

• Percentage of Participants with CR or Better

  Up to 5 years

• Percentage of Participants with Overall Response

  Up to 5 years

Study Arms (2)

Arm A: Ramantamig plus Daratumumab (Ramantamig-D)

EXPERIMENTAL

Participants will receive ramantamig D subcutaneous injection.

Drug: Ramantamig; Drug: Daratumumab

Arm B: Investigator's Choice (DVRd or DRd)

ACTIVE COMPARATOR

Participants will receive either daratumumab, bortezomib, lenalidomide, dexamethasone (DVRd) or daratumumab, lenalidomide, dexamethasone (DRd) as per investigator's choice.

Drug: Daratumumab; Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Ramantamig DRUG

Ramantamig will be administered subcutaneously.

Arm A: Ramantamig plus Daratumumab (Ramantamig-D)

Daratumumab DRUG

Daratumumab will be administered subcutaneously.

Arm A: Ramantamig plus Daratumumab (Ramantamig-D); Arm B: Investigator's Choice (DVRd or DRd)

Lenalidomide DRUG

Lenalidomide will be administered orally.

Arm B: Investigator's Choice (DVRd or DRd)

Bortezomib DRUG

Bortezomib will be administered subcutaneously or intravenously.

Arm B: Investigator's Choice (DVRd or DRd)

Dexamethasone DRUG

Dexamethasone will be administered orally or intravenously.

Arm B: Investigator's Choice (DVRd or DRd)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Lenalidomide; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Janssen Research & Development LLC Clinical trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Central Study Contacts

Study Contact

CONTACT

844-434-4210; Participate-In-This-Study1@its.jnj.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2026
• First Posted: June 24, 2026
• Study Start (Estimated): September 14, 2026
• Primary Completion (Estimated): September 4, 2030
• Study Completion (Estimated): February 2, 2035
• Last Updated: July 6, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share