This study has been transitioned to CTIS with ID 2023-503441-55-00 check the CTIS register for the current data. The primary objective is to compare the efficacy of Tec-Dara (Arm A) with DPd/DVd (Arm B) in participants who have received 1 to 3 prior…
ID
Source
Brief title
Condition
- Haematopoietic neoplasms (excl leukaemias and lymphomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to compare the efficacy of teclistamab
in combination with daratumumab SC (Tec-Dara; Arm A) with that of an
investigator*s choice of DPd or DVd (Arm B; termed DPd/DVd hereafter) as
assessed by PFS
Secondary outcome
Key secondary objectives include further comparison of efficacy as assessed by
overall response (PR or better) rate, CR or better rate,MRD -negativity rate,
PFS2, Overall survival, Time to next treatment and duration of response.
Background summary
Although the treatment of patients with multiple myeloma is getting better,
patients cannot be cured from the disease. That is why we are constantly
looking for better treatment options. One of the possibilities is to treat
people with so-called antibodies. One of the antibodies is the study drug
teclistamab.
Teclistamab (also known as JNJ-64007957) is a humanized IgG4-PAA bispecific
antibody that binds the CD3 receptor complex on T cells and BCMA on plasma
cells. With its dual binding sites, teclistamab is able to draw myeloma cells
in close proximity to CD3+ T cells, resulting in T cell activation and
subsequent lysis of BCMA+ cells that is mediated by secreted perforin and
various granzymes stored in the secretory vesicles of cytotoxic T cells.
Study objective
This study has been transitioned to CTIS with ID 2023-503441-55-00 check the CTIS register for the current data.
The primary objective is to compare the efficacy of Tec-Dara (Arm A) with
DPd/DVd (Arm B) in participants who have received 1 to 3 prior lines of
therapy, including a PI and lenalidomide.
Study design
A Phase 3 Randomized Study Comparing Teclistamab in Combination with
Daratumumab SC (Tec-Dara)
versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC,
Bortezomib,
and Dexamethasone (DVd) in Participants with Relapsed or Refractory Multiple
Myeloma.
The study will be conducted in 3 phases: Screening, Treatment, and Follow-Up.
Approximately 560 subjects will be randomized 1:1 to receive either standard
therapy with DVd or DPd (Arm B) or to receive Tec-Dara (Arm A). Decision DVd or
DPd treatment is by investigator's choice.
Intervention
Study treatment will be administered on 28-day cycles for Tec-Dara (Arm A) and
DPd (Arm B). For DVd (Arm B), study treatment will be administered on 21-day
cycles for Cycles 1 to 8 and 28-day cycles for Cycles 9+. Teclistamab will be
administered subcutaneously using a weight-based dose schedule as detailed in
the protocol.
Study burden and risks
Taking into account the measures taken to minimize risk to participants in this
study, the potential risks identified for combination therapy of teclistamab
and daratumumab are justified by the anticipated benefits that may be afforded
to participants with relapsed/refractory multiple
myeloma. The addition of teclistamab to daratumumab SC offers a unique
mechanism of action of T -cell redirection that could lead to synergistic
antimyeloma effects. A short course of steroids may prevent long-term
steroid-induced toxicities.
There is potential risk for overlapping toxicities with the planned study
drugs, specifically the unknown effect of daratumumab SC on CRS (which is the
main toxicity of concern with teclistamab) and sARRs. The risk mitigation
measures planned for the experimental arm:
- Implementation of step-up doses of teclistamab to reduce risk or severity of
CRS
- Note that teclistamab has demonstrated mostly low-grade CRS in studies to date
- Staggered initiation of daratumumab SC and teclistamab therapy to reduce the
risk of overlapping toxicity
- Implementation of pretreatment medications to reduce risk or severity of
sARRs and CRS for the first 2 weeks of therapy
- Provision of specific monitoring guidelines for participants during the first
few doses of teclistamab when CRS risk is highest
- SC administration of daratumumab reduces the risk of high-grade sARRs
- Note that sARRs have been observed at low frequency and low grade to date
with participants treated with teclistamab in studies.
- Robust management strategies for potential toxicities
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Listed location countries
Age
Inclusion criteria
- >=18 years of age.
- Documented multiple myeloma as defined by the criteria below:
a. Multiple myeloma diagnosis according to the IMWG diagnostic criteria
b. Measurable disease at screening as defined by any of the following:
1) Serum M-protein level >=0.5 g/dL (central laboratory); or
2) Urine M-protein level >=200 mg/24 hours (central laboratory); or
3) Serum immunoglobulin free light chain >=10 mg/dL (central laboratory) and
abnormal serum immunoglobulin kappa lambda free light chain ratio.
- Received 1 to 3 prior line(s) of antimyeloma therapy (Appendix 6) including a
PI and lenalidomide.
a. Participants who have received only 1 line of prior line of antimyeloma
therapy must be lenalidomide refractory (ie, have demonstrated progressive
disease by IMWG criteria during treatment or within 60 days of completion of
lenalidomide-containing regimen). Progression on or within 60 days of the last
dose of lenalidomide given as maintenance will meet this criterion.
- Documented evidence of progressive disease based on investigator*s
determination of response by IMWG criteria on or after their last regimen.
- Have an ECOG performance status score of 0, 1, or 2 at screening and
immediately prior to the start of administration of study treatment (Appendix
7).
- Have clinical laboratory values meeting the criteria specified in the
protocol.
Exclusion criteria
- Contraindications or life-threatening allergies, hypersensitivity, or
intolerance to any study drug or its excipients,
Additional exclusion criteria pertaining to specific study drugs include:
a. A participant is not eligible to receive DPd as control therapy if any of
the following are present:
1) Contraindications or life-threatening allergies, hypersensitivity, or
intolerance to pomalidomide (intolerance defined as prior therapy discontinued
due to any AE related to pomalidomide)
2) Disease that is considered refractory to pomalidomide per IMWG (progression
during treatment or within 60 days of completing treatment with pomalidomide).
b. A participant is not eligible to receive DVd as control therapy if any of
the following are present:
1) Contraindications or life-threatening allergies, hypersensitivity, or
intolerance to bortezomib (intolerance defined as prior therapy discontinued
due to any AE related to bortezomib)
2) Grade 1 peripheral neuropathy with pain or Grade >=2 peripheral neuropathy as
defined by NCI-CTCAE Version 5.0
3) Disease that is considered refractory to bortezomib per IMWG (progression
during treatment or within 60 days of completing treatment with bortezomib).
4) Received a strong CYP3A4 inducer (see Section 6.12.3.3) within 5 half-lives
prior to randomization.
c. A participant is not eligible for this study if they are refractory to both
pomalidomide and bortezomib.
- Received any prior BCMA-directed therapy.
- Has disease that is considered refractory to an anti-CD38 monoclonal antibody
per IMWG (progression during treatment or within 60 days of completing therapy
with an anti-CD38 monoclonal antibody).
- Received a cumulative dose of corticosteroids equivalent to >=140 mg of
prednisone within 14 days before randomization.
- Received a live, attenuated vaccine within 4 weeks before randomization.
- Plasma cell leukemia at the time of screening, Waldenström*s
macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, M-protein, and skin changes), or primary amyloid light chain
amyloidosis.
For a full list of exclusion criteria, please refer to section 5.2 of the study
protocol
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-503441-55-00 |
| EudraCT | EUCTR2020-004742-11-NL |
| ClinicalTrials.gov | NCT05083169 |
| CCMO | NL78480.056.21 |