Limited-duration Teclistamab

Official title

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

Overview

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.

Interventions

• 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 biom

Primary outcome measures

• Failure free at six months following teclistamab discontinuation [Time frame: Six months after teclistamab discontinuation]

Secondary outcome measures (8)

• Time to progression and progression-free survival [Time frame: Two years after teclistamab discontinuation.]
• Time-to-treatment failure [Time frame: Two years after teclistamab discontinuation]
• Re-initiation rate [Time frame: Six months after teclistamab discontinuation]
• Rate of response to teclistamab re-initiation [Time frame: Two years after teclistamab discontinuation]
• Rate of infectious complications [Time frame: 12 months after teclistamab discontinuation]
• Rate and type of clinical complications of progressive disease [Time frame: Six months after teclistamab discontinuation]
• Quality of life [Time frame: Two years after teclistamab discontinuation]
• Mean percent change in peripheral blood studies [Time frame: Two years after teclistamab discontinuation]

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:

• ≥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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

United States · 5 centers

• University of Arkansas for Medical Sciences — Little Rock
• University of Iowa Hospitals and Clinics — Iowa City
• Columbia University — New York
• Abramson Cancer Center at University of Pennsylvania — Philadelphia
• Thomas Jefferson University, Honickman Center — Philadelphia

Publications

• Razzo BM, Midha S, Portuguese AJ, Grajales-Cruz AF, De Menezes Silva Corraes A, Costello P, Liu Y, Sperling AS, Nadeem O, Dima D, Banerjee R, Cowan AJ, Afrough A, Anderson LD Jr, Lieberman-Cribbin A, Kaur G, Goyal A, Atrash S, Ferreri CJ, Voorhees PM, Pasvolsky O, Lee HC, Patel KK, Julian KL, Forsberg PA, Herr MM, Chhabra S, Parrondo RD, Lin Y, Chen A, Susanibar-Adaniya SP, Khouri J, Raza S, Anwer PMID 40629516

Identifiers

NCT: NCT05932680 · UPCC 08423 · IRB 853459

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗