NCT07463807

Testing the Investigational Medication Combination of Teclistamab and Pomalidomide Compared to the Usual Treatment (Carfilzomib, Pomalidomide, and Dexamethasone) for Patients With Multiple Myeloma Who Have Relapsed Shortly After Treatment

Phase Ib/II Fixed Duration Study of Teclistamab/Pomalidomide (TP) Versus Carfilzomib/Pomalidomide/Dexamethasone (KPd) in Early Relapse of Multiple Myeloma

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 162 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the toxicity of teclistamab and pomalidomide (TP) combination therapy in multiple myeloma (MM) patients in early relapse after one or two lines of therapy and establish the pomalidomide dose to be used with teclistamab in the Phase II portion of the trial. (Phase Ib) II. To determine whether patients with MM in early relapse after one or two lines of therapy who are randomized to teclistamab and pomalidomide (TP) compared to carfilzomib, pomalidomide, and dexamethasone (KPd) have superior efficacy measured by minimal residual disease (MRD)-negative complete response status after 9 cycles of treatment. (Phase II) SECONDARY OBJECTIVES: I. To determine whether patients with MM in early relapse who are randomized to TP compared to KPd have superior progression-free survival (PFS). II. To determine whether patients with MM in early relapse who are randomized to TP compared to KPd have superior overall survival (OS). III. To evaluate safety and compare toxicity rates between TP and KPd arms. IV. To evaluate response by International Myeloma Working Group (IMWG) uniform response criteria. OUTLINE: PHASE IB: Patients are assigned to 1 of 2 arms. ARM A and B: Patients teclistamab subcutaneously (SC) on days 1, 4, 7, 14, and 21 of cycle 1, days 1, 8, 15, and 22 of cycle 2, days 1 and 15 of cycles 3-6, then on day 1 of remaining cycles. Starting with cycle 2, patients receive pomalidomide orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are randomized to 1 of 2 arms. ARM C: Patients teclistamab SC on days 1, 4, 7, 14, and 21 of cycle 1, days 1, 8, 15, and 22 of cycle 2, days 1 and 15 of cycles 3-6, then on day 1 of subsequent cycles. Starting with cycle 2, patients receive pomalidomide PO QD on days 1-21 of subsequent cycles. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM D: Patients receive carfilzomib intravenously (IV) on days 1, 2, 8, and 15 of cycle 1, on days 1, 8, and 15 of cycle 2, then on days 1 and 15 of subsequent cycles, pomalidomide PO QD on days 1-21 and dexamethasone PO or IV on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo urine and blood sample collection, fludeoxyglucose F-18 (FDG) positron emission tomography (PET)/computed tomography (CT), and bone marrow biopsy and/or aspiration throughout the study. After completion of study treatment, patients are followed every 3 months for up to year 2, every 6 months for years 2-5, then yearly for up to 10 years from date of registration/randomization.

Conditions

• Recurrent Multiple Myeloma
• Refractory Multiple Myeloma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo urine and blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow biopsy and/or aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy and/or aspiration
DRUG	Carfilzomib	Given IV
PROCEDURE	Computed Tomography	Undergo FDG PET/CT
DRUG	Dexamethasone	Given PO or IV
PROCEDURE	FDG-Positron Emission Tomography	Undergo FDG PET/CT
OTHER	Fludeoxyglucose F-18	Given FDG
DRUG	Pomalidomide	Given PO
DRUG	Teclistamab	Given SC

Timeline

• Start date: 2026-06-26
• Primary completion: 2026-08-31
• Completion: 2026-08-31
• First posted: 2026-03-11
• Last updated: 2026-04-13

Regulatory

• FDA-regulated drug study