This phase Ib/II trial compares the effect of teclistamab and pomalidomide to standard treatment with carfilzomib, pomalidomide and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed). 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. Pomalidomide is in a class of medications called immunomodulatory agents. It works by helping the immune system kill cancer cells and by helping the bone marrow to produce normal blood cells. Carfilzomib blocks the action of enzymes called proteasomes, which may help keep cancer cells from growing and may kill them. It is a type of proteasome inhibitor. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving teclistamab and pomalidomide may be safe, tolerable and improve response by lowering myeloma cells to undetectable levels when compared to standard treatment with carfilzomib, pomalidomide and dexamethasone in treating patients with relapsed multiple myeloma.
Patient must be ≥ 18 years of age
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Patient must have an identifiable dominant sequence (clonotype) established based on Adaptive Biotechnologies clonoSEQ® assay for Phase II only
Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma.
None
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo urine and blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow biopsy and/or aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy and/or aspiration
Carfilzomib
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo FDG PET/CT
Dexamethasone
DrugGiven PO or IV
FDG-Positron Emission Tomography
Procedure/SurgeryUndergo FDG PET/CT
Fludeoxyglucose F-18
Other interventionGiven FDG
Pomalidomide
DrugGiven PO
Teclistamab
DrugGiven SC
Incidence of dose limiting toxicities (Phase Ib)
Will be defined by the toxicities (per National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0)possibly, probably, or definitely related to the combination regimen after the teclistamab dose is stable and the combination of teclistamab and pomalidomide has been administered for one full cycle.
Rate of minimal residual disease negativity (Phase II)
Will be determined by the Adaptive Biotechnologies clonoSEQ, registered trademark, assay results. Analysis will be a comparison using Cochran-Mantel-Haenszel (CMH) test, stratified on prior autologous stem cell transplant, CD38 antibody refractory and high risk at registration. The CMH estimate of odds ratio with 80% confidence interval (CI) and p-value will be reported. The treatment effect will be evaluated in select subgroups including stratification factors as well as PI-exposed or not and 1st or 2nd relapse. Additionally, logistic regression will be used to assess the treatment effect after adjusting for known prognostic factors.
Progression-free survival
Will be estimated in the eligible and randomized population using the Kaplan-Meier method and compared between arms using the stratified log-rank test. Stratified cox proportional hazards (PH) regression will be used to produce the treatment hazard ratio (HR; Arm C/Arm D) along with the 90% CI, provided PH assumption is valid. Sensitivity analyses excluding untreated patients will be conducted.
Overall survival
Will be estimated in the eligible and randomized population using the Kaplan-Meier method and compared between arms using the stratified log-rank test. Stratified cox PH regression will be used to produce the treatment HR (Arm C/Arm D) along with the 90% CI, provided PH assumption is valid. Sensitivity analyses excluding untreated patients will be conducted.
Incidence of adverse events (AE)
Will be graded according to NCI CTCAE v 5.0 and classified by Medical Dictionary for Regulatory Activities system organ class. Maximum grade toxicity by AE type will be tabulated. Summaries (count and percentages) will be reported by AE type by arm. Rates of maximum grade 3 or higher (including grade 5) non-hematologic, hematologic and overall toxicity will be calculated along with 90% CIs. AEs will be further analyzed by arm in subsets of serious adverse events per protocol, lethal AEs and treatment-emergent adverse events status.
Best response
Will be based on International Myeloma Working Group uniform criteria and will include rates of partial response (PR), very good PR, complete response (CR) and stringent CR.
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