CAR-T cell therapy is an emerging treatment modality in relapsed and refractory multiple myeloma (MM). CAR-T therapy in MM relies on directing autologous T-cells to detect and clear myeloma cells expressing B-cell Maturation Antigen (BCMA). While BCMA CAR-T cell-treated patients achieve an excellent overall response rate, their response is often not durable. NT-I7 promotes CAR-T cell expansion and efficacy in pre-clinical lymphoma models. In patients receiving CD19-directed CAR-T therapy for lymphoma, NT-I7 augmented CAR-T expansion while being safe and tolerable. The impact of NT-I7 on BCMA CAR-T cells in multiple myeloma is unknown.
This is a two-stage, multicenter, phase IB study, with a dose escalation stage leading into a two-arm, double blind, placebo-controlled, randomized dose expansion stage testing the safety and toxicity of adding NT-I7 to BCMA CAR-T therapy in patients with relapsed and refractory multiple myeloma. The hypothesis is that NT-I7 will promote CAR-T expansion and persistence which will enhance clearance of MM, while maintaining a favorable safety and toxicity profile. Patients receiving standard of care BCMA CAR-T (cilta-cel) will be randomized to either NT-I7 or placebo. Correlative studies will evaluate CAR-T cell expansion, persistence, immune-phenotype, function and correlate with clinical outcomes.
Diagnosis of multiple myeloma with measurable disease by IMWG criteria.
Eligible for standard of care, FDA-approved BCMA CAR-T cell therapy with ciltacabtagene autoleucel.
Patients enrolling in the dose escalation stage must have received at least two prior lines of treatment and be penta-drug exposed (i.e. exposure to at least 5 active anti-myeloma drugs, excluding corticosteroids and melphalan and including, at minimum, a proteasome inhibitor, an immunomodulatory drug, and a CD38 monoclonal antibody).
Life expectancy ≥ 12 weeks per assessment from the enrolling physician.
Received prior BCMA-directed therapy.
Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
Currently receiving or have received any other investigational agents within 14 days prior to CAR-T infusion.
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to NT-I7or other agents used in the study.
Sequential
NT-I7
DrugNT-I7 will be supplied by NeoImmuneTech Inc
Placebo
DrugPlacebo will be supplied by NeoImmuneTech Inc
Rate of non-hematologic grade ≥3 treatment-related adverse events (excluding expected conditioning-related AEs)
Graded per CTCAE v 5.0.
Recommended phase II dose (Dose escalation stage only)
The recommended phase II dose (RP2D) is defined as the highest tested dose level or the dose level immediately below the dose level at which 2 or more patients experience dose-limiting toxicity during the dose-limiting toxicity (DLT) assessment period.
MRD negativity by clonoSEQ (10^5 cutoff)
MRD negativity by clonoSEQ (10^6 cutoff)
Number of participants with stringent complete response (sCR) by IMWG criteria
* Stringent complete response requires all of the following: * CR as defined below * Normal free light chain ratio (0.26-1.65) * Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence * Complete response (CR) requires all of the following: * Negative immunofixation on the serum and urine * \<5% plasma cells in the bone marrow aspirate * Disappearance of any soft tissue plasmacytomas * Normalization of the serum free light chain ratio in patients who lack measurable M protein in the serum and urine at baseline
Progression-free survival (PFS)
* PFS is defined as the length of time between randomization and disease progression or death from any cause. * Progressive disease per IMWG criteria.
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Washington University School of Medicine
Lead sponsor
NeoImmuneTech
Collaborator
Swim Across America
Collaborator
