LINVOSELTAMAB for Relapsed/refractory multiple myeloma

Inclusion criteria

• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1\n- Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria\n- Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria as defined in the protocol.\n- Phase 1, Part 1 (Dose Escalation): Patients with MM who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease or intolerance of the therapy and including either: a. Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a PI, an IMiD, and an anti-CD38 antibody, OR b. Progression on or after an anti-CD38 antibody and have disease that is \"double refractory\" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The anti-CD38 antibody may have been administered alone or in combination with another agent such as a proteasome inhibitor (PI). Refractory disease is defined as lack of response or relapse within 60 days of last treatment.\n- Phase 1, Part 2 (SC Administration): Patients with MM whose disease meets the following criteria: a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple-refractory, defined as being refractory to prior treatment with at least 1 anti-CD38 antibody, a PI, and an IMiD.\n- Phase 2 (Cohorts 1 and 2): Patients with MM whose disease meets the following criteria: a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody. *Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.\n- Phase 2 (Cohort 3): Patients with MM whose disease meets the following criteria: Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody. * Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.\n- AND, if patients have relapsed after a BCMA-directed CAR-T cellular therapy then: • Treatment with a CAR-T must have been associated with a response of PR or better, and • If CAR-T cellular therapy was the most recent prior therapy, excluding corticosteroids, then treatment must have been a minimum of 60 days prior to treatment with linvoseltamab\n- Other protocol defined inclusion criteria apply"}

Exclusion criteria

• {"criterion_text":"- Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis, (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)\n- Patients with known MM brain lesions or meningeal involvement\n- Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA)\n- Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs. Note: BCMA antibody-drug conjugates are not excludedand BCMA-directed CAR-T treatment is not excluded in Phase 2 Cohort 3.\n- History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment\n- Other protocol defined exclusion criteria apply"}

Primary endpoints

• {"endpoint_text":"- Phase 1: Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period","definition_or_measurement_approach":"Incidence measured from first dose through end of the DLT observation period (as defined in protocol)."}
• {"endpoint_text":"- Phase 1: Incidence and severity of treatment-emergent adverse events (TEAEs)","definition_or_measurement_approach":"Assessment of incidence and severity of TEAEs (treatment-emergent adverse events) during Phase 1."}
• {"endpoint_text":"- Phase 1: Incidence and severity of adverse events of special interest (AESI)","definition_or_measurement_approach":"Assessment of incidence and severity of AESIs during Phase 1."}
• {"endpoint_text":"- Phase 1, Part 2: Assessment of the pharmacokinetics (PK) of linvoseltamab","definition_or_measurement_approach":"Pharmacokinetic characterization of linvoseltamab in Part 2 (SC administration) measured by serum concentrations over time."}
• {"endpoint_text":"- Phase 2, cohorts 1 and 2: Objective response rate (ORR) as determined by an Independent Review Committee (IRC)","definition_or_measurement_approach":"ORR determined by IRC using IMWG response criteria."}
• {"endpoint_text":"- Phase 2, cohort 3: Incidence and severity of cytokine release syndrome (CRS) with linvoseltamab","definition_or_measurement_approach":"Assessment of incidence and severity of CRS in cohort 3 as observed during treatment."}
• {"endpoint_text":"- Phase 2, cohort 3: ORR of IV linvoseltamab as assessed by investigator","definition_or_measurement_approach":"Investigator-assessed ORR using IMWG criteria."}

Secondary endpoints

• {"endpoint_text":"- Phase 1 part 1 and Phase 2: Concentrations of linvoseltamab in the serum over time","definition_or_measurement_approach":"Serum concentration-time profiles of linvoseltamab measured at specified PK timepoints."}
• {"endpoint_text":"- Phase 1 and Phase 2: Incidence over time of anti-drug antibodies (ADAs) to linvoseltamab","definition_or_measurement_approach":"Incidence of ADAs measured longitudinally over study period."}
• {"endpoint_text":"- Phase 1 and Phase 2: Titer of anti-drug antibodies (ADAs) to linvoseltamab over time","definition_or_measurement_approach":"ADA titers measured over time."}
• {"endpoint_text":"- Phase 1 and Phase 2: Incidence of neutralizing antibodies (Nab) to linvoseltamab over time","definition_or_measurement_approach":"Incidence of neutralizing antibodies assessed longitudinally."}
• {"endpoint_text":"- Phase 2, cohorts 1 and 2: Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria","definition_or_measurement_approach":"DOR per IRC using IMWG criteria."}
• {"endpoint_text":"- Phase 1 and Phase 2: DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria","definition_or_measurement_approach":"Investigator-determined DOR using IMWG criteria."}
• {"endpoint_text":"- Phase 2: Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria","definition_or_measurement_approach":"PFS per IRC using IMWG criteria."}
• {"endpoint_text":"- Phase 1 and Phase 2: PFS as determined by an investigator, measured using the IMWG criteria","definition_or_measurement_approach":"Investigator-determined PFS using IMWG criteria."}
• {"endpoint_text":"- Phase 1: Rate of minimal residual disease (MRD) negative status, as determined by the investigator using the IMWG criteria","definition_or_measurement_approach":"Rate of MRD-negative status assessed by investigator using IMWG criteria."}
• {"endpoint_text":"- Phase 2: Rate of MRD negative status","definition_or_measurement_approach":"Rate of MRD-negative status as defined in protocol."}
• {"endpoint_text":"- Phase 1 and Phase 2: Overall survival (OS)","definition_or_measurement_approach":"Overall survival measured from treatment start to death from any cause."}
• {"endpoint_text":"- Phase 1, part 1 dose level 7 (DL7): ORR as measured as determined by blinded IRC, as measured using the IMWG criteria","definition_or_measurement_approach":"ORR at DL7 determined by blinded IRC using IMWG criteria."}
• {"endpoint_text":"- Phase 1 and Phase 2: ORR as determined by the investigator, measured using the IMWG criteria","definition_or_measurement_approach":"Investigator-assessed ORR per IMWG criteria."}
• {"endpoint_text":"- Phase 2: Effects of linvoseltamab on health-related quality of life (HRQoL) and patient-reported symptoms and functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)","definition_or_measurement_approach":"HRQoL assessed by EORTC QLQ-C30 questionnaire."}
• {"endpoint_text":"- Phase 2: Effects of linvoseltamab on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20])","definition_or_measurement_approach":"HRQoL assessed by QLQ-MY20 module."}
• {"endpoint_text":"- Phase 2: Effects of linvoseltamab on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L])","definition_or_measurement_approach":"HRQoL assessed by EQ-5D-3L instrument."}
• {"endpoint_text":"- Phase 2: Change in patient-reported global health status/QoL per EORTC QLQ-C30","definition_or_measurement_approach":"Change from baseline in global health status per EORTC QLQ-C30."}
• {"endpoint_text":"- Phase 2: Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30","definition_or_measurement_approach":"Time to definitive deterioration per EORTC QLQ-C30."}
• {"endpoint_text":"- Phase 2: Effects of linvoseltamab on patient-reported functions and symptoms per EORTC QLQ-C30","definition_or_measurement_approach":"Patient-reported functions and symptoms per EORTC QLQ-C30."}
• {"endpoint_text":"- Phase 2: Effects of linvoseltamab on patient-reported functions and symptoms per QLQ-MY20","definition_or_measurement_approach":"Patient-reported functions and symptoms per QLQ-MY20."}
• {"endpoint_text":"- Phase 2: Incidence and severity of TEAEs with linvoseltamab","definition_or_measurement_approach":"Incidence and severity of treatment-emergent adverse events measured during Phase 2."}
• {"endpoint_text":"- Phase 2: Incidence and severity of AESIs with linvoseltamab","definition_or_measurement_approach":"Incidence and severity of adverse events of special interest measured during Phase 2."}

Spain

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

21-11-2025

Processing Time Days

457

Number Of Sites

6

Number Of Participants

3

Belgium

Earliest CTIS Part Ii Submission Date

21-08-2024

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

600

Number Of Sites

2

Number Of Participants

13

Primary sponsor

Full Name

Regeneron Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Syneos Health Inc.

Responsibilities

Full service CRO, Pharmacovigilance services, Regulatory management and submissions outside US, Translation management.

Name

Parexel International (IRL) Limited

Responsibilities

Full service CRO for Japan only. Regulatory management and submissions, translations of all applicable documents. Safety reporting

Name

Iqvia Rds Inc.

Responsibilities

Independent Scientific Review

Name

Iqvia Inc.

Responsibilities

Sample analysis, lab kits, lab manuals, third party sample management

Third parties

• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Sample analysis, lab kits, lab manuals, third party sample management","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"Assay setup and development, t-cell foundation/MM panel development and counting","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"Independent Scientific Review","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"Assay development and validation","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Full service CRO, Pharmacovigilance services, Regulatory management and submissions outside US, Translation management.","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"Investigational Product Packaging & Labeling","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"Full service CRO for Japan only. Regulatory management and submissions, translations of all applicable documents. Safety reporting","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"IxRS (Interactive Voice/Web Response System)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Inc.","duties_or_roles":"Sample analysis, lab kits, lab manuals, third party sample management","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Management and central review of imaging and efficacy labs, evaluate evidence relating to effectiveness","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"MRD NGS Testing","organisation_type":"Pharmaceutical company"}