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

NCT07463807 | Not Yet Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2026-01300EAA242U10CA180820
• Study Type: interventional
• Target: 162
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Refractory Multiple Myeloma; Recurrent Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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.

  During cycle 2 (cycle length = 28 days)

• 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.

  After 9 cycles of treatment (cycle length = 28 days)

Secondary Outcomes (4)

• Progression-free survival

  From randomization until the earlier of progression or death due to any cause or censored at date of last disease evaluation, assessed up to 10 years

• Overall survival

  From randomization to death due to any cause, or censored at date last known alive, assessed up to 10 years

• Incidence of adverse events (AE)

  Up to 30 days after last dose of study treatment

• Best response

  By cycles 12 and 24 (cycle length = 28 days)

Study Arms (3)

Arm D (carfilzomib, pomalidomide, dexamethasone)

ACTIVE COMPARATOR

Patients receive carfilzomib 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, FDG PET/CT, and bone marrow biopsy and/or aspiration throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Carfilzomib; Procedure: Computed Tomography; Drug: Dexamethasone; Procedure: FDG-Positron Emission Tomography; Other: Fludeoxyglucose F-18; Drug: Pomalidomide

Arms A and B (teclistamab, pomalidomide)

EXPERIMENTAL

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 remaining cycles. Starting with cycle 2, patients receive pomalidomide PO 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. Additionally, patients undergo urine and blood sample collection, FDG PET/CT, and bone marrow biopsy and/or aspiration throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: FDG-Positron Emission Tomography; Other: Fludeoxyglucose F-18; Drug: Pomalidomide; Drug: Teclistamab

Arms C (teclistamab, pomalidomide)

EXPERIMENTAL

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. Additionally, patients undergo urine and blood sample collection, FDG PET/CT, and bone marrow biopsy and/or aspiration throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: FDG-Positron Emission Tomography; Other: Fludeoxyglucose F-18; Drug: Pomalidomide; Drug: Teclistamab

Interventions

Pomalidomide DRUG

Given PO

Also known as: 4-Aminothalidomide, Actimid, CC 4047, CC-4047, CC4047, Imnovid, Pomalyst

Arm D (carfilzomib, pomalidomide, dexamethasone); Arms A and B (teclistamab, pomalidomide); Arms C (teclistamab, pomalidomide)

Teclistamab DRUG

Given SC

Also known as: JNJ 64007957, JNJ-64007957, JNJ64007957, Teclistamab-cqyv, Tecvayli

Arms A and B (teclistamab, pomalidomide); Arms C (teclistamab, pomalidomide)

Biospecimen Collection PROCEDURE

Undergo urine and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm D (carfilzomib, pomalidomide, dexamethasone); Arms A and B (teclistamab, pomalidomide); Arms C (teclistamab, pomalidomide)

Carfilzomib DRUG

Given IV

Also known as: Carfilnat, CFZ, Kyprolis, PR 171, PR-171, PR171

Arm D (carfilzomib, pomalidomide, dexamethasone)

Computed Tomography PROCEDURE

Undergo FDG PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm D (carfilzomib, pomalidomide, dexamethasone); Arms C (teclistamab, pomalidomide)

Dexamethasone DRUG

Given PO or IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, LenaDex, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm D (carfilzomib, pomalidomide, dexamethasone)

FDG-Positron Emission Tomography PROCEDURE

Undergo FDG PET/CT

Also known as: FDG, FDG-PET, FDG-PET Imaging

Arm D (carfilzomib, pomalidomide, dexamethasone); Arms A and B (teclistamab, pomalidomide); Arms C (teclistamab, pomalidomide)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and/or aspiration

Arm D (carfilzomib, pomalidomide, dexamethasone); Arms A and B (teclistamab, pomalidomide); Arms C (teclistamab, pomalidomide)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and/or aspiration

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Arm D (carfilzomib, pomalidomide, dexamethasone); Arms A and B (teclistamab, pomalidomide); Arms C (teclistamab, pomalidomide)

Fludeoxyglucose F-18 OTHER

Given FDG

Also known as: 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18

Arm D (carfilzomib, pomalidomide, dexamethasone); Arms A and B (teclistamab, pomalidomide); Arms C (teclistamab, pomalidomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patient must have multiple myeloma and meet both of the following criteria for the original diagnosis of myeloma following the International Myeloma Working Group (IMWG) myeloma diagnostic criteria:
• Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma.
• Tissue biopsy of any bone lesion or extramedullary plasmacytoma if applicable (positive/negative for clonal plasma cells)
• Any one or more of the following symptomatic myeloma-defining events that prompted initiation of therapy as well as end-organ damage:
• Anemia (hemoglobin value of \> 2 g/dL below the lower limit of normal, or a hemoglobin value \< 10 g/dL)
• Hypercalcemia (serum calcium \> 1 mg/dL higher than the upper limit of normal or \> 11 mg/dL)
• Bone disease (one or more osteolytic lesions on skeletal radiography, CT, or FDG-PET/CT)
• Renal dysfunction (creatinine clearance \< 40 mL/min or serum creatinine \> 2 mg/dL).
• Clonal bone marrow plasma cells (BMPCs) ≥ 60%
• Involved/uninvolved serum free light chain ratio ≥ 100
• \> 1 focal lesions on magnetic resonance imaging (MRI) studies ≥ 5 mm
• NOTE: Patients with smoldering myeloma (serum m protein ≥ 3 gm/dL or bone marrow plasma cells ≥ 10% or greater plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) and monoclonal gammopathy of undetermined significance (serum m protein \< 3 gm/dL and bone marrow plasma cells \< 10% or greater plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) are not eligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Specimen Handling; Biopsy; carfilzomib; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Fluorodeoxyglucose F18; pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Deoxyglucose; Deoxy Sugars; Carbohydrates

Study Officials

• Murali Janakiram

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Phase Ib safety lead in dose finding phase followed by a randomized phase II study

Study Record Dates

• First Submitted: March 7, 2026
• First Posted: March 11, 2026
• Study Start (Estimated): June 26, 2026
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: May 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share