Limited-duration Teclistamab

NCT05932680 | Recruiting Phase 2 DMC

• 2 other identifiers: UPCC 08423IRB 853459
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (1)

• Failure free at six months following teclistamab discontinuation

  Failure-free survival is defined as the rate of evaluable individuals who have not experienced any of the following predefined failure events within 6 months of discontinuing teclistamab. Failure is defined as earliest occurrence of any of the following: Participants who progress by IMWG criteria after discontinuing teclistamab, failure to achieve at least minimal response within 90 days after reinitiating teclistamab or failure to resume teclistamab within 90 days of IMWG-defined disease progression. Participants who reinitiate teclistamab due to rise in disease markers before IMWG criteria for disease progression are met, disease progression by IMWG criteria after reinitiation of teclistamab. Initiation of non-teclistamab systemic multiple myeloma therapy. Failure date will be defined as the date of initiating subsequent therapy. Death due to complications of multiple myeloma, teclistamab therapy, or infection

  Six months after teclistamab discontinuation

Secondary Outcomes (8)

• Time to progression and progression-free survival

  Two years after teclistamab discontinuation.

• Time-to-treatment failure

  Two years after teclistamab discontinuation

• Re-initiation rate

  Six months after teclistamab discontinuation

• Rate of response to teclistamab re-initiation

  Two years after teclistamab discontinuation

• Rate of infectious complications

  12 months after teclistamab discontinuation

Study Arms (1)

Off Drug Surveillance

EXPERIMENTAL

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.

Other: Off Drug Surveillance

Interventions

Off Drug Surveillance 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.

Off Drug Surveillance

Eligibility Criteria

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

You may qualify if:

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

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (5)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

Columbia University

New York, New York, 10032-3702, United States

RECRUITING

Abramson Cancer Center at University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Thomas Jefferson University, Honickman Center

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

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

Study Officials

• Alfred Garfall, MD

  Penn Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leonard Fiannaca, MS

CONTACT

215-662-3173; Leonard.Fiannaca@pennmedicine.upenn.edu

Alfred Garfall, MD

CONTACT

215-349-8334; Alfred.Garfall@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Teclistamab is the study drug. The intervention is the cessation of the drug.

Study Record Dates

• First Submitted: June 8, 2023
• First Posted: July 6, 2023
• Study Start: July 5, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Locations

US (5)