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

Official title

Phase 2/3, Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Etentamig and Daratumumab (Etentamig+D) Compared to Daratumumab, Lenalidomide, and Dexamethasone (DRd) in Subjects With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant

Overview

Multiple myeloma (MM) is a cancer of the blood's plasma cells. The cancer is typically found in the bones and bone marrow (the spongy tissue inside of the bones) and can cause bone pain, fractures, infections, weaker bones, and kidney failure. This is a study to determine the adverse events, change in disease activity, and pharmacokinetics of Etentamig in adult participants with MM. Etentamig is an investigational drug being developed for the treatment of MM. This study is broken into 2 phases; phase 2 with 3 study arms and phase 3 with 2 study arms. Participants in phase 2 will receive 1 of 3 doses of etentamig in combination with daratumumab. Participants in phase 3 will receive etentamig at RP3D in combination with daratumumab, or daratumumab, lenalidomide, and dexamethasone (DRd). Around 660 adult participants with MM will be enrolled at approximately 155 sites worldwide Participants in phase 2 will receive 1 of 3 doses of etentamig as intravenous (IV) infusions, combination with subcutaneous (SC) injections of daratumumab. Participants in phase 3 will receive RP3D doses of etentamig as IV infusions, combination with SC injections of daratumumab, or SC injections of daratumumab, capsules of lenalidomide, and tablet/ IV injections of dexamethasone (DRd). The study duration is approximately 16 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.

Interventions

• Drug Etentamig
  Intravenous (IV) Infusion
• Drug Lenalidomide
  Oral Capsule
• Drug Daratumumab
  Subcutaneous Injection
• Drug Dexamethasone
  Oral Tablet
• Drug Dexamethasone
  IV Injection

Primary outcome measures

• Phase 2 and 3: Percentage of Participants with Adverse Events (AE)s [Time frame: Up to Approximately 16 Years]
• Phase 2: Change in Clinical Activity [Time frame: Up to Approximately 52 weeks]
• Phase 3: Minimal Residual Disease (MRD) Negative CR Rate [Time frame: Up to Approximately 52 weeks]
• Phase 3: Progression-Free Survival (PFS) [Time frame: Up to Approximately 130 Months]

Secondary outcome measures (12)

• Phase 2: MRD Negative CR Rate [Time frame: Up to Approximately 52 Weeks]
• Phase 2: PFS [Time frame: Up to Approximately 130 Months]
• Phase 2: Sustained MRD Negativity Rate [Time frame: Up to Approximately 12 Months]
• Phase 2: Area Under the Serum Concentration-Time Curve (AUC) [Time frame: Up to Approximately 12 Months]
• Phase 2: Overall Survival (OS) [Time frame: Up to Approximately 16 Years]
• Phase 2: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability [Time frame: Up to Approximately 16 Years]
• Phase 2: Maximum Observed Serum Concentration (Cmax) [Time frame: Up to Approximately 12 Months]
• Phase 2: Time to Cmax (Time to Maximum Observed Concentration, Tmax) [Time frame: Up to Approximately 12 Months]
• Phase 2: Positive Anti-Drug Antibodies (ADAs) [Time frame: Up to Approximately 90 days after the last dose of study treatment]
• Phase 2: Negative ADAs [Time frame: Up to Approximately 90 days after the last dose of study treatment]
• Phase 2: Neutralizing Anti-Drug Antibodies (NAbs) [Time frame: Up to Approximately 90 days after the last dose of study treatment]
• Phase 3: OS [Time frame: Up to Approximately 16 Years]

Eligibility criteria

Inclusion criteria

• Participants must have confirmed new diagnosis of multiple myeloma (NDMM) according to the International Myeloma Working Group (IMWG) diagnostic criteria, and per investigator's judgement, participant is not suitable to receive high-dose chemotherapy and stem cell transplantation due to factors likely to have a negative impact on tolerability of high dose chemotherapy and autologous stem cell transplants (ASCT).
• IMWG Myeloma Frailty Index Score of >= 1
• All participants must have measurable disease per central laboratory with at least 1 of the following assessed within 28 days prior to enrollment:

• Serum M-protein >= 0.5 g/dL (>= 5 g/L).
• Urine M-protein >= 200 mg/24 hours.
• Serum free light chain (FLC) >= 100 mg/L (>= 10 mg/dL) (involved light chain) and an abnormal serum kappa lambda ratio only for participants without measurable serum or urine M-protein.

Exclusion criteria

• Prior or current systemic therapy or stem cell transplant (SCT) for multiple myeloma or any plasma cell dyscrasia other than short course of corticosteroids
• Participant treated with any investigational treatment within 30 days or 5 half-lives of the treatment (whichever is longer) prior to the first dose of study treatment or is currently enrolled in another clinical study
• Participant who has known active central nervous system involvement of MM.
• Participant who has history of clinically significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, pulmonary, or hepatic disease within the last 6 months that, in the investigator's opinion, would adversely affect the participant's participation in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 17 centers

• Mayo Clinic Hospital Scottsdale /ID# 278349 — Scottsdale
• Cedars-Sinai Medical Center /ID# 278238 — Los Angeles
• Colorado Blood Cancer Institute /ID# 279080 — Denver
• Winship Cancer Institute of Emory University /ID# 277667 — Atlanta
• Fort Wayne Medical Oncology And Hematology /ID# 278141 — Fort Wayne
• Minnesota Oncology - Minneapolis Clinic /ID# 278720 — Minneapolis
• Mayo Clinic Hospital Rochester /ID# 277886 — Rochester
• Icahn School of Medicine at Mount Sinai /ID# 277844 — New York
• … and 9 more centers

France · 15 centers

• Centre Hospitalier Annecy Genevois /ID# 278406 — Epagny Metz Tessy
• Centre Hospitalier De Dunkerque-Hospital Alexandra Lepeve /ID# 278399 — Dunkirk
• Chu De Lille - Hopital Claude Huriez /ID# 278413 — Lille
• CHU de Montpellier - Hopital Saint Eloi /ID# 278415 — Montpellier
• CHRU Tours - Hopital Bretonneau /ID# 279274 — Tours
• CH Bretagne Atlantique /ID# 278422 — Vannes
• Centre Hospitalier Universitaire de Bordeaux /ID# 278419 — Pessac
• Centre Hospitalier Universitaire de Poitiers /ID# 278398 — Poitiers
• … and 7 more centers

Spain · 12 centers

• Complejo Hospitalario Universitario de Santiago /ID# 278531 — Santiago de Compostela
• Institut Catala d'Oncologia (ICO) - Badalona /ID# 278522 — Badalona
• Hospital Universitario Marques de Valdecilla /ID# 278535 — Santander
• Hospital Universitario de Gran Canaria Doctor Negrín /ID# 278527 — Las Palmas de Gran Canaria
• Clinica Universidad de Navarra - Pamplona /ID# 278583 — Pamplona
• Hospital Clinic de Barcelona /ID# 278532 — Barcelona
• Complejo Asistencial Universitario de Leon - Hospital de Leon /ID# 278534 — León
• Hospital General Universitario Gregorio Maranon /ID# 278551 — Madrid
• … and 4 more centers

Japan · 5 centers

• Nagoya City University Hospital /ID# 278188 — Nagoya
• Matsuyama Red Cross Hospital /ID# 278660 — Matsuyama
• Kurume University Hospital /ID# 278209 — Kurume-shi
• Tokai University Hospital /ID# 278157 — Isehara
• University Hospital Kyoto Prefectural University of Medicine /ID# 278156 — Kyoto

Identifiers

NCT: NCT07095452 · M25-586 · 2025-520897-21 · 2025-520897-21-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗