Clinical trial NCT05932680: Limited-duration Teclistamab
Official title: Phase 2, Single-Arm, Non-Inferiority Study Of Limited-Duration Teclistamab For Relapsed Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myeloma Multiple
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2023-07-06
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Failure free at six months following teclistamab discontinuation
timeFrame: Six months after teclistamab discontinuation
Secondary outcomes:
measure: Time to progression and progression-free survival
timeFrame: Two years after teclistamab discontinuation.
measure: Time-to-treatment failure
timeFrame: Two years after teclistamab discontinuation
measure: Re-initiation rate
timeFrame: Six months after teclistamab discontinuation
measure: Rate of response to teclistamab re-initiation
timeFrame: Two years after teclistamab discontinuation
measure: Rate of infectious complications
timeFrame: 12 months after teclistamab discontinuation
measure: Rate and type of clinical complications of progressive disease
timeFrame: Six months after teclistamab discontinuation
measure: Quality of life
timeFrame: Two years after teclistamab discontinuation
measure: Mean percent change in peripheral blood studies
timeFrame: Two years after teclistamab discontinuation
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center at University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Penn Medicine
name: Alfred Garfall, MD
role: PRINCIPAL_INVESTIGATOR
References: