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Limited-Duration Teclistamab for the Treatment of Multiple Myeloma
Trial Status: active
This phase II trial compares the effect of continuing teclistamab to limited duration teclistamab in controlling multiple myeloma. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as teclistamab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Teclistamab is Food and Drug Administration (FDA)-approved as a continuous therapy for multiple myeloma. This means the drug is continued until it stops working (disease progression) to control multiple myeloma or until significant side-effects or complications develop. The information gain from this trial may help researchers learn if stopping teclistamab in multiple myeloma patients who have achieved a good response after completing 6-9 months of therapy works as well as continuing teclistamab until disease progression.
Inclusion Criteria
Participants must be age >= 18 and able to give written, informed consent
Participants must have initiated teclistamab (first full dose) 6-9 months prior to enrollment and received an average teclistamab dose of at least 1.5 mg/kg/month since the date of the first 1.5 mg/kg dose
Participants must have received a teclistamab dose within 4 weeks prior to enrollment
Participants must have had measurable disease according to IMWG criteria within 1 month prior to teclistamab initiation or first full teclistamab dose, defined as one of the following:
* Serum M-spike >= 1 g/dL
* Urine M-spike >= 200 mg/24h (as measured from 24h collection or estimated from random-sample urine protein electrophoresis (UPEP) and paired urine protein/creatinine ratio)
* Involved serum free light chain ≥ 100 mg/L if the serum free light chain ratio is abnormal
Participants must have achieved a confirmed very good partial response (VGPR) or better to teclistamab therapy at any assessment prior to enrollment and have ongoing response (i.e., no disease progression) at time of enrollment per IMWG consensus criteria
Prior to initiating teclistamab, participants must have received therapy with a proteasome inhibitor, thalidomide analog (lenalidomide or pomalidomide), and an anti-CD38 antibody and meet one of the following criteria:
* >= 3 prior lines of therapy (with lines-of-therapy delineated according to IWMG guidelines)
* Refractory to both a proteasome inhibitor and a thalidomide analog
Participants must have had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at time of teclistamab initiation; in addition, ECOG performance status must be 0-1 at time of enrollment
Participants must not have known diagnoses of systemic amyloidosis or polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome
Additional locations may be listed on ClinicalTrials.gov for NCT05932680.
I. To preliminarily assess whether rate of treatment failure of limited-duration teclistamab is non-inferior to that of historical controls who received continuous therapy.
SECONDARY OBJECTIVES:
I. To estimate parameters of disease progression and response following teclistamab discontinuation, including:
Ia. Time to progression;
Ib. Time to treatment failure;
Ic. Proportion of subjects who re-initiate teclistamab in the six months following discontinuation;
Id. Response to re-initiation of teclistamab following discontinuation.
II. To determine the rate and severity of infections, including pneumonia and severe coronavirus disease 2019 (COVID-19) infection, within 12 months of limited-duration dosing.
III. To describe the rate of clinical complications of disease progression with limited-duration therapy.
IV. To determine health-related quality of life (HRQoL) during a treatment-free interval.
V. To describe changes in hematologic and immune parameters after treatment discontinuation.
EXPLORATORY OBJECTIVES:
I. To investigate associations between transcriptomic features of the bone marrow microenvironment (e.g., cell-type composition and transcriptional states, T cell phenotypes, T cell receptor repertoire diversity) and occurrence of early multiple myeloma growth after discontinuation (i.e., need to resume teclistamab <6 months after teclistamab discontinuation due to rise in serum disease biomarkers [with or without meeting International Myeloma Working Group (IMWG) thresholds for disease progression]).
II. To explore the association between clinical re-response and other biological characteristics including BCMA expression on tumor cells and soluble BCMA (sBCMA) concentrations.
III. To evaluate the association between minimal residual disease (MRD) status at time of treatment discontinuation (as assessed by bone marrow flow cytometry with goal sensitivity of 10^-5) and early multiple myeloma growth (i.e., need to resume teclistamab < 6 months after teclistamab discontinuation).
OUTLINE:
Patients discontinue standard of care (SOC) teclistamab use and are followed clinically every month and 3 months for up to 24 months on study. Patients may reinitiate SOC teclistamab for off-drug disease growth or IMWG progression and continue follow-up during the 24 month study period. Patients undergo blood sample collection throughout the trial and may optionally undergo computed tomography (CT) or CT/positron emission tomography (PET) during screening as well as optional bone marrow biopsies and aspiration and additional blood sample collection throughout the trial.
Trial PhasePhase II
Trial TypeNot provided by clinicaltrials.gov
Lead OrganizationUniversity of Pennsylvania/Abramson Cancer Center
