This phase Ib trial tests the safety, side effects and best dose of ST-067 in combination with teclistamab and how well it works in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). ST-067 is an engineered variant of the human cytokine interleukin-18 that may help the immune system kill cancer cells. Teclistamab is a bispecific antibody that can bind to two different antigens at the same time. Teclistamab binds to B-cell maturation antigen (BCMA), a protein found on some B-cells and myeloma cells, and CD3 on T-cells (a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Giving ST-067 in combination with teclistamab may be safe, tolerable and/or effective in treating patients with relapsed or refractory multiple myeloma.
OUTLINE: This is a dose-escalation study of ST-067 in combination with teclistamab followed by a dose-expansion study. Patients receive ST-067 subcutaneously (SC) on days 1, 8, 15 and 22 of cycle 1, on days 8, 15 and 22 of cycle 2, then on days 1 and 15 of subsequent cycles. Patients also receive teclistamab SC on days 1, 3, 5, 15 and 22 of cycle 2 then on days 1, 8, 15, and 22 or on days 1 and 15 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the trial and bone marrow aspiration and biopsy during screening and on study. After completion of study treatment, patients are followed every 3 months for up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Given SC
Undergo bone marrow aspiration and biopsy
Undergo bone marrow aspiration and biopsy
Ancillary studies
Given SC
Undergo blood sample collection
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Monotherapy dose-limiting toxicities (DLT) rates
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded using American Society for Transplantation and Cellular Therapy (ASTCT) criteria, while other toxicities will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. DLT rates at each dose level will be estimated by isotonic regression by applying the pooled adjacent violators algorithm.
Time frame: Up to 28 days (cycle 1)
Combination therapy DLT rates
CRS and ICANS will be graded using ASTCT criteria, while other toxicities will be graded using CTCAE v 5.0. DLT rates at each dose level will be estimated by isotonic regression by applying the pooled adjacent violators algorithm.
Time frame: Up to 28 days (cycle 2)
Optimal biological dose (OBD)
OBD will be determined based on a composite of clinical information, including safety, tolerability, optimal biological effects without undesirable clinical effects, and biological response data.
Time frame: Up to 28 days
Incidence of adverse events (AEs)
The types, frequencies and severity of AEs will be analyzed. CRS and ICANS will be graded using ASTCT criteria, while other toxicities will be graded using CTCAE v 5.0.
Time frame: Up to 30 days after last dose of ST-067
Overall response rate (ORR)
Responses will be assessed per International Myeloma Working Group criteria. ORR will be summarized along with the 2-sided 95% exact Clopper-Pearson confidence interval.
Time frame: At months 1 and 3
Minimal residual disease (MRD) negativity
Bone marrow will be assessed using next generation sequencing for achievement of MRD negativity (threshold 10\^-5) and will be compared across all enrolled participants and within each individual.
Time frame: At 1 month after initiation of teclistamab
Duration of response (DOR)
Kaplan-Meier method will be used to analyze DOR.
Time frame: Up to 5 years
Progression-free survival (PFS)
PFS will be calculated using assessments by investigators. Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quartiles (including the median).
Time frame: From first dose of teclistamab to disease progression or death up to 5 years
Overall survival (OS)
Kaplan-Meier methodology will be used to estimate OS curves.
Time frame: From first dose of teclistamab to death up to 5 years
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