Informations générales (source: ClinicalTrials.gov)
Phase 1b Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) Plus Other Cancer Treatments for Patients With Relapsed/Refractory Multiple Myeloma
Interventional
Phase 1
Regeneron Pharmaceuticals (Voir sur ClinicalTrials)
août 2022
septembre 2034
02 septembre 2025
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)
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Jean-Marie MICHOT | 04/06/2024 12:28:15 | Contacter | ||
Critères
Tous
1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
2. Participants must have measurable disease as defined in the protocol according to
International Myeloma Working Group (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. However,
participants enrolled in the expansion portion cannot be refractory to an anti-CD38
antibody containing regimen. In addition, all participants must have at least a 6-month
washout from prior anti-CD38 antibody therapy.
Cohort 2: Prior treatment with carfilzomib is allowed if previously tolerated at the
approved full dose. Carfilzomib-refractory participants may enroll in the dose finding
portion provided they are triple-class refractory (PI, IMiD, anti-CD38 antibody).
However, participants enrolled in the dose expansion portion cannot be refractory to
carfilzomib. In addition, all participants must have at least a 6-month washout from
prior carfilzomib therapy.
Cohort 3: Prior treatment with lenalidomide is allowed if previously tolerated at the
approved full dose. However, a participant cannot be refractory to any combination
regimen that included 25 mg of lenalidomide. In addition, participants must have at least
a 6-month washout from any prior lenalidomide therapy (including maintenance therapy).
Cohort 4: Prior treatment with bortezomib is allowed if previously tolerated at the
approved full dose. Bortezomib-refractory participants may enroll in the dose finding
portion provided they are triple-class refractory (PI, IMiD, anti-CD38 antibody).
However, participants enrolled in the dose expansion portion cannot be refractory to
bortezomib. In addition, all participants must have at least a 6-month washout from prior
bortezomib therapy.
Cohort 5: Prior treatment with pomalidomide is allowed if previously tolerated at the
approved full dose. Additionally, participants must undergo at least a 6-month washout
following prior pomalidomide therapy before enrollment.
Cohort 6: Prior treatment with isatuximab is allowed if previously tolerated.
Additionally, participants must undergo at least a 3-month washout following prior
anti-CD38 antibody therapy before enrollment.
Cohort 7 and 8: RRMM with progressive disease and received at least 3 lines of therapy
including exposure to at least 1 anti-CD38 antibody, 1IMiD, 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. Dia
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 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:
1. Dose expansion: Prior treatment with a B-cell maturation antigen (BCMA) -directed CAR
T-cell therapy will not be exclusionary if completed at least 12 weeks prior to first
study treatment
Cohort 3:
1. 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:
1. Peripheral neuropathy grade ≥2
Cohort 5:
1. 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)].
NOTE: Other protocol defined inclusion/exclusion criteria apply