A Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM)

Phase 3RecruitingNCT07393282

Regeneron Pharmaceuticals270 enrolled

Overview

This study is researching an experimental drug called linvoseltamab (also called "study drug") compared to another drug called daratumumab, in participants with Smoldering Multiple Myeloma (SMM), who are at a High Risk (HR) of developing active multiple myeloma. The aim of this study is to find out whether linvoseltamab is better than daratumumab in delaying the development of MM. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

270

Conditions

High Risk Smoldering Multiple Myeloma (HR-SMM)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Eastern Cooperative Oncology Group performance status score ≤1 2. SMM diagnosis per IMWG criteria as defined in the protocol 3. Meets HR-SMM criteria by 1 of the risk models as defined in the protocol Key Exclusion Criteria: 1. Evidence of myeloma-defining events attributable to the underlying plasma cell dyscrasia, as defined in the protocol 2. Diagnosis of systemic light chain amyloidosis, Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), plasma cell leukemia, or soft tissue plasmacytoma 3. History of neurodegenerative condition, progressive multifocal leukoencephalopathy, or Central Nervous System (CNS) movement disorder 4. History of a seizure within the 12 months of randomization 5. Prior exposure to any approved or investigational treatments directed against a clonal plasma cell disorder (including but not limited to conventional chemotherapies, radiotherapy, immunomodulatory drugs, proteasome inhibitors, anti-CD38 antibodies). Ongoing treatment with other monoclonal antibodies (eg, infliximab, rituximab) or other treatments likely to interfere with study procedures or results, as described in the protocol. NOTE: Other protocol defined inclusion/exclusion criteria apply

Outcomes

Primary Outcomes

Clinical Progression Free Survival (PFS) per International Myeloma Working Group (IMWG) criteria

Time frame: Up to 5 years

Biochemical PFS per IMWG criteria

Time frame: Up to 5 years

Secondary Outcomes

Achievement of Minimal Residual Disease (MRD) Complete Response (CR) at 10^-5 per IMWG criteria

Time frame: Up to 3 years

Time to death

Time frame: Up to 9 years

Overall Response Rate (ORR) of Partial Response or better (≥PR) per IMWG criteria

Time frame: Up to 3 years

Best Overall Response (BOR) per IMWG criteria

Time frame: Up to 3 years

Achievement of MRD-negativity

Time frame: Up to 3 years

Sustained MRD-negativity

Time frame: Up to 3 years

Duration of MRD-negative CR

Time frame: Up to 3 years

Duration Of Response (DOR) per IMWG criteria

Time frame: Up to 5 years

Occurrence of Treatment-Emergent Adverse Events (TEAEs)

Time frame: Up to 3 years

Severity of TEAEs

Time frame: Up to 3 years

Occurrence of Serious Adverse Events (SAEs)

Time frame: Up to 3 years

Change from baseline score in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) scale

The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported QoL using 1 GHS/QoL scale, 5 functioning scales (physical, role, emotional, cognitive and social) and 9 symptom scales / items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer. For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 5 = "excellent" with higher scores indicating better functioning and positive changes from baseline indicate improvement.

Time frame: Up to 5 years

Change from baseline score in EORTC QLQ-C30 physical functioning scale

Time frame: Up to 5 years

Change from baseline score in EORTC QLQ-C30 role functioning scale

Time frame: Up to 5 years

Change from baseline score in EORTC QLQ-C30 emotional functioning scale

Time frame: Up to 5 years

Change from baseline score in EORTC QLQ-C30 pain scale

The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported QoL using 1 GHS/QoL scale, 5 functioning scales (physical, role, emotional, cognitive and social) and 9 symptom scales / items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer. For the 9 symptom scales, scores range from 1 = "not at all" to 9 = "very much" higher scores indicate higher symptom burden and negative changes from baseline indicate improvement.

Time frame: Up to 5 years

Change from baseline score in EORTC QLQ-C30 fatigue scale

Time frame: Up to 5 years

Change from baseline score in EORTC IL478 future perspectives scale

EORTC IL478 corresponds to the EORTC QLQ-Multiple Myeloma Module 20 (MY20) future Perspective Scale. This is a is a self-administered instrument to assess QoL in persons with MM. For the future perspective 3 items are analyzed. A high score for an item represents a high level of symptomatic problem.

Time frame: Up to 5 years

Change from baseline score in EuroQoL-5 Dimensions 5-Level Questionnaire Visual Analogue Scale (EQ-5D-5L VAS )

The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: "no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems". The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labeled "Best imaginable health state" and "Worst imaginable health state".

Time frame: Up to 5 years

Functional Assessment of Cancer Therapy (FACIT)- Item Global Population 5 (GP5) responses

FACIT-Item GP5 will be used to assess the patient-reported impact of treatment toxicity that uses a single item "I am bothered by side effects of treatment" on a 5-point scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much).

Time frame: Up to 5 years

Change from baseline in FACIT- Item GP5 score

Time frame: Up to 5 years

Concentrations of linvoseltamab in serum

Time frame: Up to 5 years

Occurrence of Anti-Drug Antibodies (ADAs) to linvoseltamab in serum

Time frame: Up to 5 years

Magnitude of ADA to linvoseltamab in serum

Time frame: Up to 5 years

A Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts