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Recruiting Phase 1

A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Participants With Multiple Myeloma That is Resistant to Current Standard of Care Treatments

NCT05137054 · tracked via the Priya Life Science Spain tracker
Phase
Phase 1
Started
2022-08-17
Last updated
2026-07-08

Condition(s) studied

Multiple Myeloma

Investigational drug(s) / intervention(s)

Linvoseltamab →Daratumumab →Carfilzomib →Lenalidomide →Bortezomib →Pomalidomide →Isatuximab →Fianlimab →Cemiplimab →Nirogacestat →Cevostamab →

Linvoseltamab: Administered per the protocol

Daratumumab: Administered per the protocol

Carfilzomib: Administered per the protocol

Lenalidomide: Administered per the protocol

Bortezomib: Administered per the protocol

Pomalidomide: Administered per the protocol

Isatuximab: Administered per the protocol

Fianlimab: Administered per the protocol

Cemiplimab: Administered per the protocol

Nirogacestat: Administered per the protocol

Cevostamab: Administered per the protocol

Study summary

This study is researching an experimental drug called linvoseltamab in combination with other drugs for the treatment of a blood cancer called multiple myeloma. Linvoseltamab has previously been studied as a single agent (without other cancer treatments) in participants with multiple myeloma that returned after prior therapies and needed to be treated again.

In the initial study, some participants treated with linvoseltamab had improvement of their myeloma, including complete responses (no evidence of myeloma in their bodies).

This study is the first time linvoseltamab will be combined with other cancer therapies.

The main goal is to understand if linvoseltamab can be given safely with other cancer treatments, and if so, what dose of linvoseltamab should be used for each combination.

The study is looking at several other research questions, including:

* How many participants treated with linvoseltamab in combination with each of the other cancer treatments have improvement of their multiple myeloma
* What side effects may happen from taking linvoseltamab together with another cancer treatment
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) less effective or could lead to side effects)

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
General Key Inclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 2. Participants must have measurable disease as defined in the protocol according to IMWG consensus criteria 3. Adequate creatinine clearance, hematologic function and hepatic function, as defined in protocol 4. Life expectancy of at least 6 months Cohort Specific Inclusion Criteria: For cohorts 1-6, each participant must have RRMM with progression following at least 3 lines of therapy, or at least 2 lines of therapy and either prior exposure to at least 1 anti-CD38 antibody, 1 immunomodulatory imide drug (IMiD) and 1 Proteasome Inhibitor (PI), or double-refractory to 1 PI and 1 IMiD, or the combination of 1 PI and 1 IMiD Cohort 1: Prior treatment with daratumumab is allowed if previously tolerated, as described in the protocol Cohort 2: Prior treatment with carfilzomib is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 3: Prior treatment with lenalidomide is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 4: Prior treatment with bortezomib is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 5: Prior treatment with pomalidomide is allowed if previously tolerated at the approved full dose, as described in the protocol Cohort 6: Prior treatment with isatuximab is allowed if previously tolerated, as described in the protocol Cohort 7 and 8: 1. For participants without measurable disease by biochemical parameters \[serum or urine M-protein, or serum involved Free Light Chain (FLC)\], presence of at least 1 soft tissue plasmacytoma with a single diameter of ≥2 cm 2. RRMM with progressive disease and received at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 IMiD, and 1 PI or triple-class refractory disease (anti-CD38 antibody, IMiD, PI) Cohort 9: Progressive RRMM in participants with triple-class refractory disease (anti-CD38 antibody, IMiD, PI) after at least 3 lines of therapy Cohort 10: Progressive RRMM after at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 IMiD, and 1 PI General Key Exclusion Criteria: 1. Diagnosis of plasma cell leukemia, primary light-chain amyloidosis (excluding myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes) 2. Participants with known MM brain lesions or meningeal involvement 3. Treatment with any systemic anti-myeloma therapy within 5 half-lives or within 21 days prior to first administration of study drug regimen, whichever is shorter 4. History of allogeneic and autologous stem cell transplantation, as described in the protocol 5. Unless stated otherwise in a specific sub-protocol, prior treatment with a T cell-based immunotherapy directed against B-Cell Maturation Antigen (BCMA) bispecific antibodies and Bispecific T-cell Engagers (BiTEs), and BCMA Chimeric Antigen Receptor (CAR) T cells (Note: BCMA antibody-drug conjugates are not excluded) 6. History of progressive multifocal leukoencephalopathy, neurodegenerative condition or Central Nervous System (CNS) movement disorder or participants with a history of seizure within 12 months prior to study enrollment are excluded 7. Live or attenuated vaccination within 28 days prior to first study drug regimen administration with a vector that has replicative potential 8. Cardiac ejection fraction \<40% by Echocardiogram (Echo) or Multigated Acquisition (MUGA) scan Cohort Specific Exclusion Criteria: Cohort 2: Dose expansion: Prior treatment with a BCMA-directed CAR T-cell therapy will not be exclusionary if completed at least 12 weeks prior to first study treatment Cohort 3: Known malabsorption syndrome or pre-existing gastrointestinal (GI) condition that may impair absorption of lenalidomide; delivery of lenalidomide via nasogastric tube or gastrostomy tube is not allowed Cohort 4: Peripheral neuropathy grade ≥2 Cohort 5: Known malabsorption syndrome or pre-existing GI conditions that may impair absorption of pomalidomide; delivery of pomalidomide via nasogastric tube or gastrostomy tube is not allowed Cohort 7: 1. Prior treatment with anti-Lymphocyte Activation Gene 3 (LAG-3) agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-Programmed cell Death Protein 1 (PD-1) antibodies is permitted, as described in the protocol 2. Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol 3. Prior solid organ transplant 4. History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies Cohort 8: 1. Prior treatment with anti-PD-1 or anti-PD-L1 agents. Prior exposure to vaccine therapies or other immune checkpoint modulating therapies such as anti-Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) antibodies is permitted, as described in the protocol 2. Encephalitis or meningitis in the year prior to enrollment 3. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to enrollment 4. Ongoing or recent (within 2 years) evidence of an autoimmune disease that has required systemic treatment with immunosuppressive agents, as described in the protocol. 5. Prior solid organ transplant 6. History of grade ≥3 immune-mediated adverse events (with the exclusion of endocrinopathies that are fully controlled by hormone replacement) from prior checkpoint inhibitor therapies Cohort 9: 1. Abnormal QT interval corrected by Fridericia's formula (QTcF), as described in the protocol 2. Use of concomitant medications that are known to prolong the QT/QTcF interval including Class Ia and Class III antiarrhythmics at the time of informed consent 3. Ongoing use or anticipated use of food or drugs that are known strong/moderate cytochrome P450 (CYP)3A4 inhibitors, or strong CYP3A inducers within 14 days prior to first dose of nirogacestat 4. Known malabsorption syndrome or existing gastrointestinal GI condition that may impair absorption of nirogacestat; delivery of nirogacestat via nasogastric tube or gastrostomy tube is not allowed Cohort 10: 1. Known or suspected active Epstein-Barr Virus (EBV) infection 2. Known history of Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) 3. Prior treatment with cevostamab or another agent with the same target \[Fragment crystallizable Receptor-like 5 (FcRH5)\] Dose finding portion: Prior treatment with any BCMA-directed immunotherapy will not be exclusionary, as described in the protocol Dose expansion portion: Prior treatment with any T cell-engaging bispecific antibody directed against BCMA will be exclusionary, as described in the protocol NOTE: Other protocol defined inclusion/exclusion criteria apply

Primary outcome measure(s)

  • Incidence of Dose Limiting Toxicities (DLTs) for each study regimen during the observation period — Up to 28 Days
    Dose finding portion only
  • Incidence of Treatment-Emergent Adverse Events (TEAEs) — Up to 5 Years
  • Severity of TEAEs — Up to 5 Years
  • Incidence of Serious Adverse Events (SAEs) — Up to 5 Years
  • Severity of SAEs — Up to 5 Years
  • Incidence of Adverse Events of Special Interest (AESIs) — Up to 5 Years
  • Severity of AESIs — Up to 5 Years
  • Incidence of laboratory abnormalities — Up to 5 Years
    ≥ grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE v5.0\]

Trial sites (42)

FacilityCityRegionStatus
Scripps Clinic Torrey Pines La Jolla California Recruiting
Winship Cancer Institute of Emory University Atlanta Georgia Recruiting
Indiana University Health Simon Cancer Center Indianapolis Indiana Recruiting
Dana Farber/Harvard Cancer Center Boston Massachusetts Recruiting
Karmanos Cancer Institute Detroit Michigan Recruiting
Mayo Clinic Rochester Minnesota Recruiting
Weill Cornell Medicine/New York Presbyterian Hospital New York New York Recruiting
New York Presbyterian Hospital Columbia University Medical Center New York New York Recruiting
University of North Carolina at Chapel Hill Chapel Hill North Carolina Recruiting
Wake Forest University Health Sciences Winston-Salem North Carolina Recruiting
The Ohio State University James Cancer Hospital Columbus Ohio Recruiting
University of Texas Southwestern Dallas Texas Recruiting
VA Puget Sound Health Care System Seattle Washington Recruiting
Centre Hospitalier Universitaire (CHU) de Poitiers Poitiers New Aquitaine Recruiting
CHU de Lille - Rue Michel Polonovski Lille Nord Suspended
Nantes University Hospital Nantes Pays de la Loire Region Recruiting
Centre Hospitalier Universitaire Angers Angers France Recruiting
CHU Montpellier - Departement D'Hematologie Montpellier France Recruiting
Saint Antoine Hospital Paris France Recruiting
Institut Gustave Roussy Villejuif France Recruiting
Hospital Henri Mondor Créteil Île-de-France Region Recruiting
Saint Louis Hospital Paris Île-de-France Region Recruiting
Hopital Necker Paris Île-de-France Region Recruiting
Evangelismos General Hospital Athens Attica Recruiting
General Hospital of Athens Alexandra Athens Greece Recruiting
Sheba Medical Center Ramat Gan Central District Recruiting
Rambam Health Care Campus Haifa Israel Recruiting
Hadassah Medical Center Jerusalem Israel Recruiting
Hospital Clinico Universitario de Santiago Santiago de Compostela A Coruna Recruiting
Hospital Germans Trias i Pujol Badalona Barcelona Recruiting
Hospital Universitario Marques de Valdecilla Santander Cantabria Recruiting
Hospital Universitario Quiron Salud Madrid Pozuelo de Alarcón Madrid Recruiting
Clinica Universidad de Navarra Pamplona Navarre Recruiting
Hospital Universitario Vall d'Hebron Barcelona Spain Recruiting
Hospital Clinic de Barcelona Barcelona Spain Recruiting
Institut Catala d'Oncologia (ICO) - Hospital Duran i Reynals, Barcelona Spain Recruiting
Universitaru Hospital La Princesa Madrid Spain Recruiting
Clinica Universidad de Navarra - Madrid Madrid Spain Recruiting
Hospital Universitario Ramon y Cajal - Servicio de Psiquiatria Madrid Spain Recruiting
University Hospital and Research Institute Madrid Spain Recruiting

+ 2 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05137054 on ClinicalTrials.gov ↗ ← All trials in Spain