This study has been transitioned to CTIS with ID 2023-503444-13-00 check the CTIS register for the current data. The primary objective of this study is to compare the efficacy of teclistamab monotherapy (Arm A) with that of an investigator*s choice…
ID
Source
Brief title
Condition
- Haematopoietic neoplasms (excl leukaemias and lymphomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is PFS, defined as the time from the date of randomization
to the date of first documented disease progression, as defined in the IMWG
2016 criteria, or death due to any cause, whichever occurs first. For
participants who have not progressed and are alive, data will be
censored at the last disease assessment before the start of any subsequent
antimyeloma therapy. Participants without any post-baseline disease assessment
will be censored at the date of randomization.
Secondary outcome
- CR or better (sCR+CR) is defined as participants who achieve a CR or better
response prior to subsequent antimyeloma therapy in accordance with the IMWG
2016 criteria.
- OS is measured from the date of randomization to the date of the
participant*s death due to any cause. If the participant is alive or the vital
status is unknown, then the participant*s data will be censored at the date the
participant was last known to be alive.
- Time to worsening of symptoms is defined as the interval from the date of
randomization to the start date of worsening in the MySIm-Q total symptom
score. Worsening is defined as a decrease in score that is at least half of
standard deviation from baseline values. Death due to disease progression will
be considered as worsening. Participants who have not met the definition of
worsening will be censored as of the last assessment date of the MySIm-Q prior
to start of subsequent anticancer treatment.
Background summary
A Phase 3 Randomized Study Comparing Teclistamab Monotherapy versus
Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone
(Kd) in Participants with Relapsed or Refractory Multiple Myeloma who have
Received 1 to 3 Prior Lines of Therapy, Including an Anti-CD38 Monoclonal
Antibody and Lenalidomide.
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 2023-503444-13-00 check the CTIS register for the current data.
The primary objective of this study is to compare the efficacy of teclistamab
monotherapy (Arm A) with that of an investigator*s choice of PVd or Kd (Arm B:
termed PVd/Kd hereafter) as assessed by PFS.
Study design
This is a randomized, Phase 3, multicenter, open-label study to evaluate
teclistamab monotherapy versus investigator*s choice of PVd or Kd. The study
will be conducted in 3 phases: Screening (up to 28 days), Treatment (until
confirmed progressive disease, death, intolerable toxicity, withdrawal of
consent, or end of the study, whichever occurs first), and Follow-up (until
death, withdrawal of consent, loss to follow-up, or end of the study, whichever
occurs first). Participants who discontinue study treatment for any reason
other than progressive disease or withdrawal of consent for study participation
will continue to be followed for response assessment until confirmed
progressive disease or start of subsequent antimyeloma therapy. After confirmed
progressive disease, participants will be followed for survival status,
subsequent antimyeloma therapies, and the occurrence of second primary
malignancies every 16 weeks until the end of the study.
An IDMC will be commissioned for this study to review cumulative safety data
periodically and the results from the prespecified interim analyses.
The overall duration of the study will be approximately 9 years.
Intervention
Study treatment will be administered on 28-day cycles for teclistamab (Arm A)
and Kd (Arm B). For PVd (Arm B), study treatment will be administered on 21-day
cycles.
At the time of screening, the investigator must declare whether the participant
will be treated with PVd or Kd should they be randomized to Arm B. The protocol
includes eligibility criteria related to investigator*s choice of PVd or Kd.
Teclistamab monotherapy (group A)
Teclistamab SC (weight-based dosing) in 28 Day Cycles
PVd (group B); 21 day cycle
Pomalidomide, Bortezomib and Dexamethasone
Kd (Group B) Includes 2 dosing options (once or twice weekly) in 28 day cycles
Carfilzomib and Dexamethasone
Study burden and risks
Arm A (Teclistamab Monotherapy)
Based on the results of Study 64007957MMY1001 (MajesTEC-1), teclistamab
monotherapy has demonstrated a high rate of deep and durable response in
heavily pre-treated patients. As teclistamab relies on the immune system of the
patient, it will be investigated if receiving teclistamab monotherapy at
earlier lines of therapy could lead to improved antimyeloma effects.
The study population for Study 64007957MMY3006 (MajesTEC-9) has a high unmet
medical need as all patients will have relapsed or refractory myeloma and prior
therapy will have included an anti-CD38 monoclonal antibody and lenalidomide,
which limits future treatment options.
Participants will be closely monitored throughout the study for both safety and
clinical benefit.
The risk mitigation measures planned for the experimental arm include:
implementation of step-up doses of teclistamab and pretreatment medications for
the first 3 doses of teclistamab to reduce risk or severity of CRS; provision
of specific monitoring guidelines for participants during the first few doses
of teclistamab when CRS risk is highest. ICANS is a potential risk to T cell
redirector therapy, often observed concurrently with or following CRS. The
above risk mitigation measures for CRS will also address the risk of ICANS
associated with teclistamab. Other measures include specification of
recommended concomitant therapies, including antimicrobial prophylaxis to
reduce risk of infection and management strategies for potential toxicities.
Taking into account the measures taken to minimize risk to participants in this
study, the potential risks identified for teclistamab monotherapy are justified
by the anticipated benefits that may be afforded to participants with
relapsed/refractory multiple myeloma.
Arm B (Investigator*s Choice of PVd or Kd)
Favorable benefit and risk profiles for PVd and Kd have been demonstrated. Kd
is approved in both the US and EU, and PVd is approved in the EU for this
patient population.
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Listed location countries
Age
Inclusion criteria
Inclusion Criteria: - Documented diagnosis of multiple myeloma as defined by
the criteria below: (a)Multiple myeloma diagnosis according to International
Myeloma Working Group (IMWG) diagnostic criteria (b) Measurable disease at
screening as defined by any of the following: (1) Serum M-protein level greater
than or equal to (>=)0.5 grams per deciliter (g/dL) (central laboratory); or
(2) Urine M-protein level >=200 milligrams (mg)/24 hours (central laboratory);
or (3) Serum immunoglobulin free light chain >=10 milligrams per deciliter
(mg/dL) (central laboratory) and abnormal serum immunoglobulin kappa lambda
free light chain ratio - Received 1 to 3 prior lines of antimyeloma therapy
including a minimum of 2 consecutive cycles of an anti- cluster of
differentiation 38 (CD38) monoclonal antibody at the approved dosing regimen in
any prior line and 2 consecutive cycles of lenalidomide in any prior line -
Documented evidence of progressive disease or failure to achieve a response to
last line of therapy based on investigator*s determination of response by
International myeloma working group (IMWG) criteria - Have an Eastern
Cooperative Oncology Group (ECOG) performance status score of 0 to 2 - A female
participant must agree not to be pregnant, breast-feeding, or plan to become
pregnant while enrolled in this study or within 6 months after the last dose of
study treatment - Must be willing and able to adhere to the lifestyle
restrictions specified in this protocol. Please refer to the protocol for full
inclusion criteria.
Exclusion criteria
Exclusion Criteria: - Received any prior B cell maturation antigen
(BCMA)-directed therapy -A participant is not eligible to receive PVd as
control therapy if any of the following are present: (1) Received prior
pomalidomide therapy, (2) Does not meet criteria for bortezomib retreatment (3)
Contraindications or life-threatening allergies, hypersensitivity, or
intolerance to pomalidomide or bortezomib, (4) Grade 1 peripheral neuropathy
with pain or Grade greater than or equal to (>=) 2 peripheral neuropathy as
defined by National Cancer Institute Common Terminology Criteria for Adverse
Events (NCI-CTCAE) Version 5.0, (5) Received a strong cytochrome P (CYP) 3A4
inducer within 5 half-lives prior to randomization; A participant is not
eligible to receive Kd as control therapy if any of the following are present:
(1) Received prior carfilzomib therapy, (2) Uncontrolled hypertension, defined
as an average systolic blood pressure greater than (>)159 millimeters of
mercury (mmHg) or diastolic blood pressure >99 mmHg despite optimal treatment
(3) Grade 2 peripheral neuropathy with pain or Grade >=3 peripheral neuropathy
as defined by NCI-CTCAE Version 5.0, (4) Contraindications or life-threatening
allergies, hypersensitivity, or intolerance to carfilzomib (intolerance defined
as prior therapy discontinued due to any adverse event [AE] related to
carfilzomib) - Central nervous system (CNS) involvement or clinical signs of
meningeal involvement of multiple myeloma. - Received a live, attenuated
vaccine within 4 weeks before randomization - Plasma cell leukemia at the time
of screening, Waldenstrom*s macroglobulinemia, polyneuropathy, organomegaly,
endocrinopathy, M-protein (POEMS) syndrome and skin changes, or primary amyloid
light chain amyloidosis - Received a maximum cumulative dose of corticosteroids
of >=140 mg of prednisone or equivalent within 14 days prior to randomization
Please refer to the protocol for full exclusion criteria.
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 | CTIS2023-503444-13-00 |
| EudraCT | EUCTR2022-000928-37-NL |
| CCMO | NL82458.056.22 |