Limited-duration Teclistamab

NCT ID: NCT05932680

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-05
• Study Completion Date: 2027-01-31

Brief Summary

This is a single-arm, non-inferiority study in which patients who have achieved a very good partial response (VGPR) or better, according to International Myeloma Working Group (IMWG) response criteria, following 6 to 9 months of treatment with teclistamab, a B-cell maturation antigen (BCMA)-directed T-cell engager (anti-BCMAxCD3 bispecific antibody), will be offered monitored drug discontinuation. Teclistamab is typically dosed on a regular schedule (every 1-4 weeks) indefinitely until disease progression ("continuous therapy"). Here, a limited-duration regimen will be studied in which patients achieving ≥VGPR after 6-9 months of standard teclistamab dosing will discontinue therapy and resume if laboratory or clinical parameters suggest early disease progression ("limited-duration therapy"). Patients will enter the clinical trial protocol after completing 6-9 months of standard teclistamab monotherapy and achieving ≥VGPR. The study's hypothesis is that the failure probability six months after stopping teclistamab in this patient population will be non-inferior compared to that of historical controls treated with continuous therapy. Reducing drug exposure may be beneficial by reducing risk of infection and reducing anti-BCMA selective pressure toward generation of BCMA-negative relapses. Analysis of minimal residual disease (MRD), tumor features, and bone marrow microenvironment parameters, which will be pursued as exploratory correlative analyses in this study, may identify factors that predict durable response to limited-duration therapy and thereby enable more precise selection of patients likely to benefit from this approach. A subset of patients will be enrolled on a biomarker study for analysis of these exploratory endpoints.

Conditions

Myeloma Multiple

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Off Drug Surveillance

Participants will stop receiving teclistamab and will be monitored closely for growth of their multiple myeloma. Participants will restart teclistamab if their multiple myeloma starts to grow.

Group Type: EXPERIMENTAL

Off Drug Surveillance

Intervention Type: OTHER

After stopping teclistamab, participants will be monitored monthly by standard serum paraprotein studies for disease progression. Participants will resume teclistamab at time of disease progression. After Teclistamab therapy re-initiation on-study, monthly response assessments and data for other study endpoints will be obtained. All participants will undergo peripheral blood collection for correlative research studies at baseline and every two months on-study. Participants who enroll on the biomarker sub-study will undergo bone marrow examination and peripheral blood collection for correlative studies at study entry, at time of disease progression and at six months from enrollment.

Interventions

Off Drug Surveillance

After stopping teclistamab, participants will be monitored monthly by standard serum paraprotein studies for disease progression. Participants will resume teclistamab at time of disease progression. After Teclistamab therapy re-initiation on-study, monthly response assessments and data for other study endpoints will be obtained. All participants will undergo peripheral blood collection for correlative research studies at baseline and every two months on-study. Participants who enroll on the biomarker sub-study will undergo bone marrow examination and peripheral blood collection for correlative studies at study entry, at time of disease progression and at six months from enrollment.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Participants must be age ≥18 and able to give written, informed consent.
• Participants must have initiated teclistamab (first full dose) 6-9 months prior to enrollment and received an average teclistamab dose of at least 1.5 mg/kg/month since the date of the first 1.5 mg/kg dose.
• Participants must have received a teclistamab dose within 4 weeks prior to enrollment.
• Participants must have had measurable disease according to IMWG criteria within 1 month prior to teclistamab initiation or first full teclistamab dose
• Participants must have achieved a confirmed VGPR or better to teclistamab therapy at any assessment prior to enrollment and have ongoing response (i.e., no disease progression) at time of enrollment per IMWG consensus criteria (Appendix 14.3).
• Prior to initiating teclistamab, participants must have received therapy with a proteasome inhibitor, thalidomide analog (lenalidomide or pomalidomide), and an anti-CD38 antibody and meet one of the following criteria:

1. ≥3 prior lines of therapy (with lines-of-therapy delineated according to IWMG guidelines)

2. Refractory to both a proteasome inhibitor and a thalidomide analog.

• Participants must have had an ECOG performance status of 0-2 at time of teclistamab initiation; in addition, ECOG performance status must be 0-1 at time of enrollment.
• Participants must not have known diagnoses of systemic amyloidosis or POEMS syndrome.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abramson Cancer Center at Penn Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alfred Garfall, MD

Role: PRINCIPAL_INVESTIGATOR

Penn Medicine

Locations

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status: RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status: RECRUITING

Columbia University

New York, New York, United States

Site Status: RECRUITING

Abramson Cancer Center at University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Thomas Jefferson University, Honickman Center

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Leonard Fiannaca, MS

Role: CONTACT

Leonard.Fiannaca@pennmedicine.upenn.edu

215-662-3173

Alfred Garfall, MD

Role: CONTACT

Alfred.Garfall@pennmedicine.upenn.edu

215-349-8334

Facility Contacts

Carolina Schinke, MD

Role: primary

CDSchinke@uams.edu

501-686-8230

Francesca Nugent

Role: primary

francesca-nugent@uiowa.edu

319-356-1727

George Mellgard

Role: primary

sym9026@nyp.org

212-342-5162

Alfred Garfall, MD

Role: primary

alfred.garfall@pennmedicine.upenn.edu

215-349-8334

Ariel Kobylak

Role: primary

Ariel.Kobylak@jefferson.edu

267-408-7961

Lizza Waugh

Role: backup

Elizabeth.Waugh@jefferson.edu

Other Identifiers

IRB 853459

Identifier Type: OTHER

Identifier Source: secondary_id

UPCC 08423

Identifier Type: -

Identifier Source: org_study_id