ELDORADO: Elranatamab Versus Daratumumab in Combination With RVd Lite for Newly Diagnosed Transplant Ineligible/Deferred Multiple Myeloma

NCT07247097 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-699
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is being done to compare the efficacy and safety of the combination of elranatamab, lenalidomide, bortezomib, dexamethasone versus the combination of daratumumab, lenalidomide, bortezomib, dexamethasone for patients with newly diagnosed, transplant ineligible/deferred multiple myeloma.

Conditions

Multiple Myeloma; Newly Diagnosed Multiple Myeloma; Transplant Ineligible; Newly Diagnosed Multiple Myeloma (NDMM)

Keywords

NDMM; multiple myeloma; ELDORADO; RVd lite; transplant ineligible/deferred

Outcome Measures

Primary Outcomes (1)

• Proportion Patients who test Negative for Minimal Residual Disease (MRD) at 10^-5 after 4 Treatment Cycles

  Evaluated at 1 x 10\^-5 using next generation sequencing (NGS) to detect clonal sequences. The proportions will be compared using the Cochran-Mantzel-Haenszel test, stratified by the randomization stratification factors. A one-sided significance level of 0.05 will be used. Patients without successful baseline minimal residual disease (MRD) testing will not be evaluated for MRD response. Proportion patients who test negative for MRD at 10\^-5 after 4 treatment cycles will be compared between the elran-RVd lite arm and the dara-RVd lite arm.

  Day 1 of Cycle 1 (each cycle is 28 days) to Day 28 of Cycle 4.

Secondary Outcomes (10)

• Progression-Free Survival (PFS)

  Day 1 of Cycle 1 (each cycle is 28 days) to documentation of disease progression or death from any cause (up to 5 years). Patients who have not progressed or died are censored at the date last known progression-free.

• Overall Survival (OS)

  Day 1 of Cycle 1 (each cycle is 28 days) to documentation of death due to any cause or censored at the date last known alive, up to 5 years from study registration.

• Overall Response Rate (ORR)

  Day of initiation of first response to the first documentation of disease progression or death, up to 5 years after registration. Patients who have not progressed or died are censored at the date last known progression-free.

• Proportion Patients who test Negative for Minimal Residual Disease (MRD) at 10^-5 after 12 Treatment Cycles

  Day 1 of Cycle 1 (each cycle is 28 days) to Day 28 of Cycle 12.

• Proportion Patients who test Negative for Minimal Residual Disease (MRD) at 10^-6 after 4 Treatment Cycles

  Day 1 of Cycle 1 (each cycle is 28 days) to Day 28 of Cycle 4.

Study Arms (2)

Elranatamab with lenalidomide, bortezomib, and dexamethasone (elra-RVd lite)

EXPERIMENTAL

The first 10 patients will enroll in the elranatamab arm for a one 14-day safety run-in cycle. Elranatamab and dexamethasone will be administered at pre-determined doses on days 1, 4, and 8 of the cycle. After randomization occurs, patients in the elra-RVd lite arm will complete 24 cycles (each cycle is 28 days) of treatment. On day 1 of each cycle and day 15 of cycle 1, the pre-determined dose of elranatamab will be administered via subcutaneous injection. On days 1-21 of each cycle, patients will take the pre-determined dose of oral lenalidomide. One days 1, 8, and 15 of cycles 1-8, the pre-determined dose of bortezomib will be administered via subcutaneous injection. After completion of 24 treatment cycles, patients who have had two MRD negative tests, one year apart, may discontinue treatment and enter the observation phase of the trial. Patients who have not had two MRD negative tests one year apart, may continue elranatamab lenalidomide treatment for another 24 cycles.

Drug: Elranatamab (PF-06863135); Drug: Lenalidomide; Drug: Bortezomib for Injection; Drug: Dexamethasone

Daratumumab with lenalidomide, bortezomib, and dexamethasone (dara-RVd lite)

EXPERIMENTAL

After randomization occurs, patients in the dara-RVd lite arm will complete 24 cycles (each cycle is 28 days) of treatment. On days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+, the pre-determined dose of daratumumab will be administered via subcutaneous injection. On days 1-21 of each cycle, patients will take the pre-determined dose of oral lenalidomide. One days 1, 8, and 15 of cycles 1-8, the pre-determined dose of bortezomib will be administered via subcutaneous injection. On days 1, 2, 8, 9, 15, 16 of cycles 3+, as well as days 22 and 23 of cycles 1 and 2, patients will take the pre-determined dose of oral dexamethasone.

Drug: Daratumumab and Hyaluronidase-fihj; Drug: Lenalidomide; Drug: Bortezomib for Injection; Drug: Dexamethasone

Interventions

Elranatamab (PF-06863135) DRUG

Elranatamab is a bispecific IgG2 kappa monoclonal antibody.

Elranatamab with lenalidomide, bortezomib, and dexamethasone (elra-RVd lite)

Daratumumab and Hyaluronidase-fihj DRUG

Daratumumab is an immunoglobulin G1 kappa human monoclonal antibody against CD38 antigen.

Daratumumab with lenalidomide, bortezomib, and dexamethasone (dara-RVd lite)

Lenalidomide DRUG

Lenalidomide is a thalidomide analogue and an immunomodulatory agent with antiangiogenic properties.

Daratumumab with lenalidomide, bortezomib, and dexamethasone (dara-RVd lite); Elranatamab with lenalidomide, bortezomib, and dexamethasone (elra-RVd lite)

Bortezomib for Injection DRUG

Bortezomib for injection is a small molecule proteosome inhibitor.

Daratumumab with lenalidomide, bortezomib, and dexamethasone (dara-RVd lite); Elranatamab with lenalidomide, bortezomib, and dexamethasone (elra-RVd lite)

Dexamethasone DRUG

Dexamethasone is a synthetic adrenocortical steroid.

Daratumumab with lenalidomide, bortezomib, and dexamethasone (dara-RVd lite); Elranatamab with lenalidomide, bortezomib, and dexamethasone (elra-RVd lite)

Eligibility Criteria

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

You may qualify if:

• Participants must be at least 18 years of age
• Newly diagnosed multiple myeloma, with monoclonal plasma cells in the bone marrow ≥10% or a biopsy proven plasmacytoma and either CRAB criteria or biomarker of malignancy
• a. CRAB criteria, one or more of the following: i. Hypercalcemia: serum calcium (\>1 mg/dL) higher than the upper limit of normal or \>11 mg/dL ii. Renal insufficiency: creatinine clearance \<40 mL/min (calculated per local practice) or serum creatinine \>2 mg/dL iii. Anemia: hemoglobin value \>2 g/dL below the lower limit of normal or hemoglobin \<10 g/dL iv. Bone lesions: one or more lytic lesions on skeletal radiography, CT, or PET CT b. Biomarker of malignancy (one or more of the following): i. Clonal bone marrow plasma cells ≥60% ii. Involved:uninvolved serum free light chain ratio ≥100 iii. \>1 focal lesion on magnetic resonance imaging (MRI)
• Measurable disease as defined by one of the following:
• Serum monoclonal protein ≥0.5 g/dL. For IgA monoclonal protein, total IgA \>500 mg/dL is allowable.
• Urine monoclonal protein ≥200 mg/24 hours
• Involved serum free light chain ≥100 mg/L with abnormal free light chain ratio
• Not considered eligible for high dose melphalan and autologous stem cell transplant per treating investigator or plan for deferred high dose melphalan and autologous stem transplant
• ECOG performance status of 0-2
• ANC ≥1000/μL. G-CSF is not permitted within 14 days of screening.
• Platelet count ≥75,000/µL. Platelet count ≥50,000/µL is permitted if bone marrow is \>50% involved. Platelet transfusion and thrombopoietin receptor agonists are not permitted within 7 days of screening.
• Hemoglobin ≥ 8 g/dL. Red blood cell transfusions are permitted to meet eligibility criteria.
• Calculated creatinine clearance of ≥ 30 mL/min, not requiring dialysis, with calculation per local practice.
• Serum bilirubin values \< 1.5 x ULN. Isolated bilirubin x 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%. Patients with elevated bilirubin due to Gilbert's syndrome may be permitted with PI approval (e.g. total bilirubin \<3 mg/dL and normal direct bilirubin); and
• Serum aspartate transaminase (ALT) and aspartate transaminase (AST) values \< 2.5 × the upper limit of normal (ULN) of the institutional laboratory reference range.

You may not qualify if:

• Prior or current systemic therapy for any plasma cell disorder. An exception is emergency use of corticosteroids (equivalent to dexamethasone 40 mg daily for four days). After discussion with the principal investigator. one cycle of standard of care myeloma therapy (without anti-CD38 monoclonal antibody) is permissible to allow for stabilization of disease, during screening/prior to enrollment.
• Pregnancy, currently breastfeeding, or planned breastfeeding.
• Participant plans to father a child while enrolled in the study or within 100 days after last dose of study treatment.
• Prior history of malignancies, other than MM, unless the patient has completed definitive treatment and has been free of the disease for ≥3 years. Patients who are free of disease \<3 years may enroll after approval of the PI (e.g. localized breast cancer considered to have very low risk of recurrence). Exceptions include the following (i.e. the following are eligible to participate):
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Ductal carcinoma in situ of the breast
• Incidental histologic finding of prostate cancer (T1a or T1b) managed with surveillance
• Other malignancies of clinically localized disease may be permitted to enroll after discussion with the Sponsor-Investigator
• Patients with plasma cell leukemia at time of screening, POEMS syndrome, or primary AL amyloidosis are excluded from this trial.
• Seropositive for HIV infection.
• Hepatitis B viral load positive.
• Hepatitis C viral load positive.
• Peripheral neuropathy ≥grade 2.
• Patient has a history of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness that could preclude study participation, pose an undue medical hazard, or interfere with the interpretation of the study results, including, but not limited to:

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Pfizer: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Lenalidomide; Bortezomib; Injections; 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; Drug Administration Routes; Drug Therapy; Therapeutics; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Andrew Yee, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Yee, MD

CONTACT

617-726-4000; AYEE1@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: November 25, 2025
• Study Start: April 15, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2035
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (3)