Limited-duration Teclistamab

Phase 2, Single-Arm, Non-Inferiority Study Of Limited-Duration Teclistamab For Relapsed Refractory Multiple Myeloma

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.

Study Overview

• Status: Recruiting
• Conditions: Myeloma Multiple
• Intervention / Treatment: Other: Off Drug Surveillance

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alfred Garfall, MD; Phone Number: 215-349-8334; Email: alfred.garfall@pennmedicine.upenn.edu
• Study Contact Backup: Name: Leonard Fiannaca, MS; Phone Number: 215-662-3173; Email: Leonard.Fiannaca@pennmedicine.upenn.edu

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas for Medical Sciences
      • Contact: Carolina Schinke, MD; Phone Number: 501-686-8230; Email: CDSchinke@uams.edu
      • Principal Investigator: Carolina Schinke, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals and Clinics
      • Principal Investigator: Hira Shaikh, MD
      • Principal Investigator: Christopher Strouse, MD
      • Contact: Francesca Nugent; Phone Number: 319-356-1727; Email: francesca-nugent@uiowa.edu
  • New York
    • New York, New York, United States, 10032-3702
      • Recruiting
      • Columbia University
      • Principal Investigator: Divaya Bhutani, MD
      • Principal Investigator: Rajshekar Chakraborty, MD
      • Contact: George Mellgard; Phone Number: 212-342-5162; Email: sym9026@nyp.org
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Abramson Cancer Center at University of Pennsylvania
      • Contact: Alfred Garfall, MD; Phone Number: 215-349-8334; Email: alfred.garfall@pennmedicine.upenn.edu
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University, Honickman Center
      • Contact: Lizza Waugh; Email: Elizabeth.Waugh@jefferson.edu
      • Principal Investigator: Beatrice Razzo, MD
      • Principal Investigator: Adam Binder, MD
      • Contact: Ariel Kobylak; Phone Number: 267-408-7961; Email: Ariel.Kobylak@jefferson.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression and progression-free survival	Time-to-progression and progression-free survival by IMWG criteria from time of teclistamab discontinuation, using the best response to initial teclistamab course as the baseline for scoring disease progression.	Two years after teclistamab discontinuation.
Time-to-treatment failure	Time-to-treatment failure as defined in the primary endpoint	Two years after teclistamab discontinuation
Re-initiation rate	Proportion of subjects who re-initiate teclistamab within six months following discontinuation	Six months after teclistamab discontinuation
Rate of response to teclistamab re-initiation	Among subjects with IMWG-defined measurable disease at time of teclistamab re-initiation, overall response rate (PR or better) and clinical benefit rate (minimal response or better) to teclistamab upon re-initiating therapy.	Two years after teclistamab discontinuation
Rate of infectious complications	Frequency of infectious complications from time of teclistamab discontinuation.	12 months after teclistamab discontinuation
Rate and type of clinical complications of progressive disease	Frequency of the type and rate of clinical complications of progressive disease (e.g., new osteolytic lesions) from time of teclistamab discontinuation through 6 months post-discontinuation.	Six months after teclistamab discontinuation
Mean percent change in peripheral blood studies	Mean percent change in peripheral blood cell counts, immunoglobulin levels, and T cell counts (total and CD4/CD8 subsets) from the time of enrollment through teclistamab resumption and through the end-of-study.	Two years after teclistamab discontinuation
Quality of life	QOL is measured using the MM-FACT instrument. Health-related quality of life (HRQoL) as measured by Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) questionnaire score at enrollment and monthly post-enrollment assessments. The higher the score, the better the quality of life. Two scores will be derived - FACT-MM Trial Outcome Index (TOI) (range: 0-112) and FACT-MM total score (range: 0-164).	Two years after teclistamab discontinuation

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Alfred Garfall, MD, Penn Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: June 8, 2023
• First Submitted That Met QC Criteria: June 27, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma
• Other Study ID Numbers: UPCC 08423; IRB 853459 (Other Identifier: University of Pennsylvania)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No