Trial Title:
Outpatient Administration of Teclistamab or Talquetamab for Multiple Myeloma
NCT ID:
NCT05972135
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Conditions: Keywords:
Teclistamab (TECVAYLI™)
Humanized IgG-4 PAA bispecific antibody
CD3 receptor complex
RRMM-Relapsed or Refractory Multiple Myeloma
MM-Multiple Myeloma
Tocilizumab prophylaxis
CRS- Cytokine Release Syndrome
Neurologic toxicity
ICANS-Immune Effector Cell-associated Neurotoxicity Syndrome
Talquetamab (TALVEY™)
GPRC5D
BCMA
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Teclistamab
Description:
Teclistamab will be administered subcutaneously at step-up doses on Day 1, Day 4 and Day
8, one week after first treatment dose and weekly thereafter. In participants who have a
partial response (PR) or better after 6 months of therapy, dosing frequency may be
reduced to every 2 weeks.
Arm group label:
Teclistamab
Other name:
(TECVAYLI™)
Intervention type:
Drug
Intervention name:
Talquetamab
Description:
Talquetamab will be administered subcutaneously at step-up doses on Day 1, Day 4, Day 8
and Day 15, one week after first treatment dose and every 2 weeks thereafter. In
participants who have a very good partial response (VGPR) or better after Cycle 4, dosing
frequency may be reduced to every 4 weeks
Arm group label:
Talquetamab
Other name:
TALVEY™
Intervention type:
Drug
Intervention name:
Tocilizumab
Description:
Tocilizumab will be administered as a pretreatment medication in advance of
administration of the first step-up dose of teclistamab or talquetamab on Cycle 1 Day 1.
Arm group label:
Talquetamab
Arm group label:
Teclistamab
Other name:
Actemra
Summary:
This is a phase II study to evaluate the outpatient administration of Teclistamab or
Talquetamab in Multiple Myeloma patients
Detailed description:
- This is a two-arm, non-randomized, multicenter, prospective study in adult patients
with RRMM, who are administered Teclistamab (TECVAYLI™) or Talquetamab (TALVEY™), in
the post-marketing setting.
- Teclistamab (TECVAYLI™) is a humanized IgG-4 PAA bispecific antibody desitned to
target the CD3 receptor complex on T cells and BCMA on B-lineage cells.
- Talquetamab (TALVEY™) is a humanized IgG-4 bispecific antibody designed to target
the CD3 receptor complex on T cells and GPRC5D-expressing multiple myeloma (MM)
cells This study will investigate the use of prophylactic tocilizumab to reduce the
incidence and severity of CRS associated with teclistamab or talquetamab
administration, to enable administration of the step-up dosing regimen of
teclistamab or talquetamab in an outpatient setting.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Be ≥18 years of age (or the higher legal age in the jurisdiction in which the study
is taking place) at the time of informed consent
- Has documented diagnosis of MM according to the IMWG diagnostic criteria (Rajkumar
2011).
- Has received 4 or more prior MM therapies including a PI, IMiD and CD38 antibody.
- Has an ECOG performance status (Oken 1982) of 0 to 1.
- Measurable disease at screening, as assessed by local laboratory, defined by any of
the following:
- Serum M-protein level ≥0.5 g/dL; or
- Urine M-protein level ≥200 mg/24 hours; or
- Light chain multiple myeloma without measurable M-protein in the serum or the
urine: sFLC ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
- For participants without measurable disease in the serum, urine, or involved
FLC, presence of plasmacytomas (≥2 cm).
- Human immunodeficiency virus-positive participants are eligible if they meet all of
the following:
- No detectable viral load (i.e., <50 copies/mL) at screening
- CD4+ count >300 cells/mm3 at screening
- No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection
within 6 months of screening
- Receiving highly active antiretroviral therapy (HAART). Any changes in HAART
due to resistance/progression should occur at least 3 months prior to
enrollment. A change in HAART due to toxicity is allowed up to 4 weeks prior to
enrollment.
- Adequate organ system function
- Body weight >35 kg.
- A participant of childbearing potential must have a negative highly sensitive serum
(β-hCG) at screening and within 72 hours of the start of study treatment and must
agree to further serum or urine pregnancy tests during the study.
- A participant must agree to abide by protocol defined contraceptive requirements for
the duration of the study
- A participant must sign an ICF indicating that participant understands the purpose
of, and procedures required for, the study and is willing to participate in the
study.
- A participant is required to stay within 30 minutes of transportation to the site
and remain in the company of a competent adult at all times until 48 hours following
administration of all doses within the teclistamab or talquetamab step-up dosing
schedule
- A participant must agree to carry the study participant identification wallet card
at all times.
- A participant must comply with all the protocol requirement procedures, including
measuring and recording of body temperature and blood oxygen saturation twice daily
(≥8 hours apart) during the first 2 cycles of teclistamab or talquetamab treatment
and coming to the study site for safety assessments.
- A participant and the accompanying competent adult must be made aware of the
presenting sign sand symptoms of teclistamab- or talquetamab- associated toxicities,
including but not limited to CRS, ICANS, infections, etc. The accompanying competent
adult must watch the participant at all times for teclistamab- or talquetamab-
associated toxicities, until 48 hours after the first treatment dose of teclistamab
or talquetamab.
Exclusion Criteria:
- Has high tumor burden, defined as having ≥60% plasma cell infiltrate on the bone
marrow biopsy or aspirate, whichever is higher, or with multiple extramedullary
disease sites or plasmacytomas.
- Has a rapidly progressing disease per investigator assessment.
- Has plasma cell leukemia (>2.0×10^9/L plasma cells by standard differential),
Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, and skin changes), or primary amyloid
light-chain amyloidosis.
- Has known active CNS involvement or exhibits clinical signs of meningeal involvement
of MM.
- Has risk factors for developing clinically significant TLS and requiring management
with increased hydration, allopurinol, or rasburicase.
- Has myelodysplastic syndrome or active malignancies (ie, progressing or requiring
treatment change in the last 12 months) other than RRMM. The only allowed exceptions
are:
- Any malignancy that was not progressing nor requiring treatment change in the
last 12 months.
- Malignancies treated within the last 12 months and considered at very low risk
for recurrence:
- Non-muscle invasive bladder cancer (solitary Ta-PUNLMP or low grade, <3 cm, no
CIS).
- Skin cancer (non-melanoma or melanoma).
- Noninvasive cervical cancer.
- Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma
in situ, localized breast cancer and receiving antihormonal agents.
- Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally
only (RP/RT/focal treatment).
- Other malignancy that is considered at minimal risk of recurrence.
- Has Grade ≥3 hematologic AEs or Grade ≥3, clinically significant non-hematologic
AEs.
- Has fever or active infection (bacterial, viral, or uncontrolled systemic fungal) at
time of study enrollment.
- Has active autoimmune disease or a documented history of autoimmune disease with the
exception of vitiligo, type I diabetes, and prior autoimmune thyroiditis that is
currently euthyroid based on clinical symptoms and laboratory testing.
- Has clinically significant coagulopathy that would increase the risk of bleeding in
the setting of cytopenia.
- Shows a deterioration in neurologic status, including mental status changes such as
confusion or increased somnolence.
- Has psychiatric disorders (eg, alcohol or drug abuse), dementia, or altered mental
status that would compromise the ability to provide informed consent or comply with
the clinical protocol.
- History of stroke, transient ischemic attack or seizure within 6 months of signing
ICF.
- Presence of the following cardiac conditions:
- New York Heart Association stage III or IV congestive heart failure.
- Myocardial infarction or CABG ≤6 months prior to enrollment.
- History of clinically significant ventricular arrhythmia or unexplained
syncope, not believed to be vasovagal in nature or due to dehydration.
- History of severe non-ischemic cardiomyopathy.
- Poorly controlled coronary artery disease and/or congestive heart failure.
- Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities.
- Has hepatitis B infection (ie, HBsAg or HBV-DNA positive). In the event the
infection status is unclear, quantitative viral levels are necessary to determine
the infection status.
- Has active hepatitis C infection as measured by positive HCV-RNA testing.
Participants with a history of HCV antibody positivity must undergo HCV-RNA testing.
If a participant with history of chronic hepatitis C infection (defined as both HCV
antibody and HCV-RNA positive) completed antiviral therapy and has undetectable
HCV-RNA 12 weeks following the completion of therapy, the participant is eligible
for the study.
- Has COPD with FEV1 <50% of predicted.
- Has eGFR <20 ml/min or is dependent on dialysis.
- Has other medical issue that would impair the ability of the participant to receive
or tolerate the planned treatment at the investigational site, to understand
informed consent or any condition for which, in the opinion of the investigator,
participation would not be in the best interest of the participant (eg, compromise
the well-being) or that could prevent, limit, or confound the protocol-specified
assessments.
- For talquetamab arm only: Prior Grade 3 or higher CRS related to any T-cell
redirection (e.g., CD-3 redirection technology or CAR-T cell therapy), or any prior
GPRC5D-targeting therapy.
- Has received packed RBC or platelet transfusions within the last 7 days prior to
dosing.
- Has contraindications to the use of tocilizumab or IVIG per local prescribing
information.
- Has received live vaccine(s) within 1 month prior to screening or plans to receive
live vaccines during the study.
- Has received live, attenuated vaccine within 30 days before the first dose of
teclistamab or talquetamab. Live, attenuated influenza vaccines are permitted as
late as 30 days before the study treatment.
- Has received an investigational intervention or used an invasive investigational
medical device within 14 days before the planned first dose of study treatment or
received an investigational biological product within 14 days or 5 half-lives,
whichever is longer, before the planned study treatment, or is currently enrolled in
an investigational study.
- History of antitumor therapy as follows, before the first dose of study drug:
- Targeted therapy, epigenetic therapy, or treatment with an investigational drug
or used an invasive investigational medical device within 21 days or at least 5
half-lives, whichever is less.
- Monoclonal antibody treatment for MM within 21 days.
- Cytotoxic therapy within 21 days.
- PI therapy within 14 days.
- Immunomodulatory agent therapy within 7 days.
- For teclistamab arm only: Prior Ggene modified adoptive cell therapy (eg,
chimeric antigen receptor modified [CAR]-T cells, NK cells) within 3 months. or
BCMA therapy).
- Radiotherapy within 14 days or focal radiation within 7 days.
- For talquetamab arm only: Prior CAR-T or BCMAbispecific antibody therapy are
allowed.
- History of stem cell transplant:
- An allogeneic stem cell transplant within 6 months. Participants who received
an allogeneic transplant must be off all immunosuppressive medications for ≥42
days without signs of graft-versus-host disease.
- An autologous stem cell transplant ≤12 weeks before the first dose of study
drug.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Arizona Oncology Associates
Address:
City:
Tucson
Zip:
85711
Country:
United States
Status:
Recruiting
Facility:
Name:
Colorado Blood Cancer Institute
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Recruiting
Facility:
Name:
Rocky Mountain Cancer Center
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Recruiting
Facility:
Name:
Florida Cancer Specialists
Address:
City:
Lake Mary
Zip:
32746
Country:
United States
Status:
Recruiting
Facility:
Name:
Maryland Oncology Hematology
Address:
City:
Columbia
Zip:
21044
Country:
United States
Status:
Recruiting
Facility:
Name:
Oncology Hematology Care
Address:
City:
Cincinnati
Zip:
45242
Country:
United States
Status:
Recruiting
Facility:
Name:
Oncology Associates of Oregon
Address:
City:
Eugene
Zip:
97401
Country:
United States
Status:
Recruiting
Facility:
Name:
TriStar Bone Marrow Transplant
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Facility:
Name:
Texas Oncology - San Antonio
Address:
City:
San Antonio
Zip:
78240
Country:
United States
Status:
Recruiting
Facility:
Name:
Texas Oncology - Northeast Texas
Address:
City:
Tyler
Zip:
75702
Country:
United States
Status:
Recruiting
Facility:
Name:
Virginia Cancer Specialists
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Facility:
Name:
Virginia Oncology Associates
Address:
City:
Norfolk
Zip:
23502
Country:
United States
Status:
Recruiting
Start date:
October 23, 2023
Completion date:
February 2025
Lead sponsor:
Agency:
SCRI Development Innovations, LLC
Agency class:
Other
Collaborator:
Agency:
Janssen Research & Development, LLC
Agency class:
Industry
Source:
SCRI Development Innovations, LLC
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05972135
