Etenta-Isa-VRd in Newly Diagnosed High-Risk Multiple Myeloma (CONQUISTADOR)

A Clinical Phase I/II, Multicenter, Open-label, National Study Evaluating Quintuplet Treat-ment With ISaTuximab, Bortezomib, Lenalidomide and Dexamethasone Plus Etentamig (Etenta-Isa-VRd) in Primary DiagnOsed High-Risk Multiple Myeloma Patients

This study is researching an experimental five-drug combination called etentamig, isatuximab, bortezomib, lenalidomide, and dexamethasone. The study is focused on participants with newly diagnosed multiple myeloma (NDMM) and high-risk disease who are eligible for autologous stem cell transplantation.

Study Overview

• Status: Not yet recruiting
• Conditions: Myeloma; Myeloma Multiple
• Intervention / Treatment: Drug: Etentamig; Drug: Isatuximab; Drug: Bortezomib + Lenalidomide + Dexamethasone

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Katja Weisel; Phone Number: +4940-7410-0; Email: k.weisel@uke.de
• Study Contact Backup: Name: Lisa Leypoldt; Phone Number: +4940-7410-0; Email: l.leypoldt@uke.de

Study Locations

• Germany
  • Hamburg, Germany
    • University Medical Center Hamburg-Eppendorf
    • Contact: Katja Weisel; Phone Number: +4940-7410-0; Email: k.weisel@uke.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have confirmed diagnosis of symptomatic MM per IMWG criteria.
• Participants must have High-risk myeloma according to IMS/IMWG CGS
• Participants must be considered a candidate for high-dose chemotherapy and ASCT, as described in the protocol.
• Participants must have measurable disease as defined in the protocol. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (WHO=3 is allowed only if caused by MM and not by co-morbid conditions).
• Participants must have clinical laboratory values within a prespecified range.

Exclusion Criteria:

• Known contraindications to the use of any IMP or axMP or required concomitant drugs or supportive treatment.
• known systemic amyloidosis (except for AL amyloidosis of the skin or the bone marrow), POEMS syndrome, Waldenstrom's macroglobulinemia; primary plasma cell leukemia
• Administration of systemic therapy for multiple myeloma except osteoprotective therapy. Emergency myeloma treatment with dexamethasone is allowed according to specifications in the protocol. It is allowed to include patients after 1 cycle of any anti-myeloma first-line treatment within the specifications of the protocol
• known central nervous system involvement by MM.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose level 1 (Phase I); First dose level of etentamig to be explored in combination with Isa-VRd	Drug: Etentamig; Administered per the protocol; Drug: Isatuximab; Administered per the protocol; Drug: Bortezomib + Lenalidomide + Dexamethasone; Administered per the protocol
Experimental: Dose Level 2 (Phase I); Second dose level of etentamig to be explored in combination with Isa-VRd	Drug: Etentamig; Administered per the protocol; Drug: Isatuximab; Administered per the protocol; Drug: Bortezomib + Lenalidomide + Dexamethasone; Administered per the protocol
Experimental: RP2D in Phase II; RP2D of etentamig to be explored in combination with Isa-VRd	Drug: Etentamig; Administered per the protocol; Drug: Isatuximab; Administered per the protocol; Drug: Bortezomib + Lenalidomide + Dexamethasone; Administered per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability (Phase I)	Number of dose-limiting toxicities (DLTs) in participants and rates of adverse events (AEs) of grade ≥2 and of severe AEs in participants	through induction treatment, on average 4 months
MRD negativity (Phase II)	MRD-negativity rate after 12 cycles (with a sensitivity of <10-5)	through consolidation phase completion, an average of 1 year
PFS	Progression-free survival	up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Overall response rate	up to 10 years
CR rate	Complete Response Rate	up to 10 years
VGPR Rate	Very good partial response rate	up to 10 years
DoR	Duration of Response	up to 10 years
TTR	Time to response	up to 10 years
PFS2	Progression free survival 2	up to 10 years
OS	Overall survival	up to 10 years
MRD negativity	Minimal Residual Disease (MRD) Negativity Rate (10-5 to 10-6)	up to 10 years
Sustained MRD	Sustained MRD negativity rate (for a duration of 6-months, and multiples therof)	up to 10 years
MRD-negative CR	Rates of MRD-negative Complete Responses	up to 10 years
Sustained MRD-negative CR	Rate of Sustained MRD-negative Complete Response	up to 10 years

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Collaborators: Sanofi; AbbVie

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): September 30, 2036
• Study Completion (Estimated): December 31, 2036

Study Registration Dates

• First Submitted: April 26, 2026
• First Submitted That Met QC Criteria: May 14, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Neoplasms, Plasma Cell; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Polycyclic Compounds; Piperidines; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Bortezomib; Dexamethasone; isatuximab
• Other Study ID Numbers: CONQUISTADOR trial; 2025-523049-83-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No