Testing Teclistamab (TECVAYLI) in Combination With Iberdomide for Relapsed or Refractory Multiple Myeloma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)
About this trial
This phase Ib trial tests the safety, side effects, and best dose of iberdomide in combination with teclistamab in treating multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Iberdomide is a medication that belongs to a group of drugs known as cereblon E3 ligase modulators. Iberdomide works by targeting and destroying proteins that help myeloma cancer cells to survive. 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. Giving iberdomide in combination with teclistamab may be safe and tolerable in treating patients with relapsed or refractory multiple myeloma.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients must have histologically or cytologically confirmed multiple myeloma (MM), as defined in the International Myeloma Working Group (IMWG) criteria
If patients have undergone autologous stem cell transplant (SCT), day 0 of SCT must be > 100 days to be eligible for the study
Patients must have had disease progression after ≥ 4 prior lines of anti-myeloma treatments including one proteasome inhibitor (e.g., bortezomib, carfilzomib, ixazomib), one immunomodulatory imide drug (ImiD) (e.g., thalidomide, lenalidomide, pomalidomide [POM]), and one anti-CD38 monoclonal antibody (e.g., daratumumab, isatuximab)
Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L)
Disqualifiers
Patients who have active plasma cell leukemia, active amyloid light chain (AL) (primary) amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, myeloma protein, and skin changes), and Waldenstrom macroglobulinemia are ineligible
If a patient develops recurrent/refractory (R/R) disease while receiving the most recent line of therapy, there is no need for a washout period
Patients who have had prior anti-BCMA directed bispecific antibody (BsAb) therapy exposure (prior treatment with anti-BCMA directed antibody drug conjugate, anti-BCMA-directed chimeric antigen receptor [CAR] T cell therapy, and prior non-BCMA-targeting BsAb are permitted)
Patients who have had prior treatment with a cereblon E3 ligase modulator, including mezigdomide, iberdomide, and CFT7455 (all currently in clinical development)
Trial design
Design model
Single group
Treatments tested in this trial
Biospecimen Collection
Procedure/SurgeryUndergo blood and urine sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Computed Tomography
Procedure/SurgeryUndergo PET/CT
Iberdomide
DrugGiven PO
Magnetic Resonance Imaging
Procedure/SurgeryUndergo PET/MR
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT or PET/MR
Teclistamab
DrugGiven SC
Treatment groups
26 Participants
are divided into 1 treatment groupGroup A: Treatment (iberdomide, teclistamab)Experimental treatment 8 interventions
Trial outcomes
Primary outcomes
1
Recommended phase 2 dose (RP2D) of iberdomide when combined with teclistamab
The RP2D will be defined as the pharmacologically optimal dose of iberdomide that can be combined with teclistamab and will be selected based on all available pharmacokinetic, pharmacodynamic, target engagement, efficacy, safety and tolerability data.
Time frame
At 28 days2
Maximum tolerated dose (MTD) of iberdomide when combined with teclistamab
The MTD will be is defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 8 new patients).
Time frame
At 28 daysSecondary outcomes
1
Incidence of adverse events (AEs)
AEs will be described and graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine patterns. The relationship of the AEs to the study treatment will be taken into consideration.
Time frame
Up to 4 weeks after last dose of study treatment2
Overall response rate (ORR)
The ORR will be estimated by the total number of patients who achieve a stringent complete response, complete response, very good partial response, or partial response divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Time frame
Up to 2 years after last dose of study treatment3
Minimal residual disease (MRD) negativity
MRD negativity will be summarized descriptively at each specified timepoint.
Time frame
Up to 2 years after last dose of study treatment4
Progression-free survival (PFS)
The distribution of PFS will be estimated using the method of Kaplan-Meier.
Time frame
From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 2 years after last dose of study treatmentOther outcomes
1
Tumor immune microenvironment
Flow cytometry will be utilized to assess the tumor immune microenvironment in the bone marrow and peripheral blood at baseline and during active treatment at specified time points. Values over time will be summarized graphically and descriptively. Paired sample approaches (Wilcoxon signed rank test) will be used to assess differences over time. The relationship between changes over time in each measure with response outcome measures will be explored using Wilcoxon's rank sum test.
Time frame
Up to 2 years after last dose of study treatment2
Soluble B-cell maturation antigen levels
Values over time will be summarized graphically and descriptively. Paired sample approaches (Wilcoxon signed rank test) for these types of quantitative measures will be used to assess differences over time. The relationship between changes over time in each measure with response outcome measures will be explored using Wilcoxon's rank sum test.
Time frame
At baselineSponsors and contacts
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Source ClinicalTrials.gov