Trial Title:
Testing Teclistamab (TECVAYLI) in Combination With Iberdomide for Relapsed or Refractory Multiple Myeloma
NCT ID:
NCT06465316
Condition:
Recurrent Multiple Myeloma
Refractory Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood and urine sample collection
Arm group label:
Treatment (iberdomide, teclistamab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow aspiration and biopsy
Arm group label:
Treatment (iberdomide, teclistamab)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow aspiration and biopsy
Arm group label:
Treatment (iberdomide, teclistamab)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT or PET/CT
Arm group label:
Treatment (iberdomide, teclistamab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Iberdomide
Description:
Given PO
Arm group label:
Treatment (iberdomide, teclistamab)
Other name:
CC 220
Other name:
CC-220
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (iberdomide, teclistamab)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Treatment (iberdomide, teclistamab)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Drug
Intervention name:
Teclistamab
Description:
Given SC
Arm group label:
Treatment (iberdomide, teclistamab)
Other name:
JNJ 64007957
Other name:
JNJ-64007957
Other name:
JNJ64007957
Other name:
Teclistamab-cqyv
Other name:
Tecvayli
Summary:
This phase Ib trial tests the safety, side effects, and best dose of iberdomide in
combination with teclistamab in treating multiple myeloma that has come back after a
period of improvement (relapsed) or that does not respond to treatment (refractory).
Iberdomide is a medication that belongs to a group of drugs known as cereblon E3 ligase
modulators. Iberdomide works by targeting and destroying proteins that help myeloma
cancer cells to survive. A monoclonal antibody is a type of protein that can bind to
certain targets in the body, such as molecules that cause the body to make an immune
response (antigens). Immunotherapy with monoclonal antibodies, such as teclistamab, may
help the body's immune system attack the cancer, and may interfere with the ability of
cancer cells to grow and spread. Giving iberdomide in combination with teclistamab may be
safe and tolerable in treating patients with relapsed or refractory multiple myeloma.
Detailed description:
PRIMARY OBJECTIVE:
I. Estimate the recommended phase 2 dose (RP2D) of iberdomide in combination with
teclistamab.
SECONDARY OBJECTIVES:
I. To evaluate the safety and toxicity profile of iberdomide in combination with
teclistamab.
II. To observe and record antitumor activity.
CORRELATIVE OBJECTIVES:
I. To evaluate the changes in the tumor immune microenvironment (exhausted T-cell
phenotypes, percent T regulatory cells [T regs], T-cell activation) in peripheral blood
and bone marrow caused by the addition of iberdomide to teclistamab and how they relate
to minimal residual disease (MRD) status, responses rates and survival outcomes.
II. To evaluate soluble B-cell maturation antigen (sBCMA) levels at baseline and how they
correlate to response rates and survival outcomes in patients treated with teclistamab
plus iberdomide.
III. To identify the immunophenotypic and transcriptomic characterization of malignant
plasma cells that are resistant to teclistamab and iberdomide.
OUTLINE: This is a dose-escalation study of iberdomide in combination with teclistamab.
Patients receive teclistamab subcutaneously (SC) on days 1, 4, 7, 15 and 22 for cycle 1
and days 1, 8, 15 and 22 for subsequent cycles. Patients also receive iberdomide orally
(PO) once daily (QD) on days 1-21 for cycle 2 and beyond. Cycles repeat every 28 days for
up to 4 years in the absence of disease progression or unacceptable toxicity.
Additionally, patients undergo blood and urine sample collection, bone marrow aspiration
and biopsy and computed tomography (CT), positron emission tomography (PET)/CT or
magnetic resonance imaging (MRI) throughout the trial.
After completion of study treatment, patients are followed up every 3-6 months for up to
2 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed multiple myeloma (MM),
as defined in the International Myeloma Working Group (IMWG) criteria
- If patients have undergone stem cell transplant (SCT), day 0 of SCT must be > 100
days to be eligible for the study
- Patients must have had disease progression after ≥ 4 prior lines of anti-myeloma
treatments including one proteasome inhibitor (e.g., bortezomib, carfilzomib,
ixazomib), one immunomodulatory imide drug (ImiD) (e.g., thalidomide, lenalidomide,
pomalidomide [POM]), and one anti-CD38 monoclonal antibody (e.g., daratumumab,
isatuximab)
- Patients must have measurable disease, defined as:
- Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L)
- Urine M-protein ≥ 200 mg/24 h
- Serum free light chain (FLC) assay: "involved" FLC level ≥ 10 mg/dL (≥ 100
mg/L) and an abnormal serum free light chain ratio (< 0.26 or > 1.65)
- Note: Patients with non-secretory disease will be allowed to participate
- Age ≥ 18 years
- Because no dosing or adverse event data are currently available on the use of
iberdomide in combination with teclistamab in patients < 18 years of age,
children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60)
- Hemoglobin ≥ 7.0 g/dL (≤ 28 days prior to registration) (Without growth factor
support, blood transfusion, or platelet stimulating agents for the past 7 days,
excluding erythropoietin)
- Absolute neutrophil count ≥ 1,000/mcL (≤ 28 days prior to registration) (Without
growth factor support, blood transfusion, or platelet stimulating agents for the
past 7 days, excluding erythropoietin)
- Platelets ≥ 50,000/mcL (≤ 28 days prior to registration) (Without growth factor
support, blood transfusion, or platelet stimulating agents for the past 7 days,
excluding erythropoietin)
- Total bilirubin ≤ 2 x institutional upper limit of normal (ULN) (≤ 28 days prior to
registration)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤
3 x institutional ULN (≤ 28 days prior to registration)
- Estimated glomerular filtration rate (eGFR) > 30 mL/min (≤ 28 days prior to
registration)
- Spot urine (albumin/creatine ratio) ≤ 500mg/g (56 mg/mmol) OR urine dipstick
negative/trace (if > 1+ only eligible if confirmed ≤ 500 mg/g (56 mg/mmol) by
albumin/creatinine ratio (spot urine from first void) (≤ 28 days prior to
registration)
- Note: Laboratory results obtained during screening should be used to determine
eligibility criteria. In situations where laboratory results are outside the
permitted range, the investigator may re-test the subject and the subsequent within
range screening result may be used to confirm eligibility
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patients with treated brain metastases are eligible if follow-up brain imaging done
a minimum of 28 days after completion of central nervous system (CNS)-directed
therapy shows no evidence of progression
- Patients with new or progressive brain metastases (active brain metastases) or
leptomeningeal disease are eligible if the treating physician determines that
immediate CNS specific treatment is not required and is unlikely to be required
during the first cycle of therapy
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class II or better
- Based on the mechanism of action, teclistamab may cause fetal harm when administered
to a pregnant woman. Females of child-bearing potential (FCBP): should use effective
contraception during treatment with teclistamab and for 5 months after the last
dose. FCBP should not breast feed during treatment with teclistamab and for 5 months
after the last dose. Should a FCBP become pregnant or suspect she is pregnant while
she or her partner is participating in this study, she should inform her treating
physician immediately. The effects of iberdomide on the developing human fetus are
unknown. However, IMiDs are known to be teratogenic. FCBP must have a negative serum
or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days
prior to starting iberdomide, and again within 24 hours. FCBP must either commit to
continued abstinence from heterosexual intercourse or begin two acceptable methods
of birth control-one highly effective method and one additional effective method-at
the same time, at least 28 days before starting iberdomide, while taking iberdomide,
and for 28 days following discontinuation from the study. Examples of highly
effective methods are intrauterine device, hormonal contraceptives, tubal ligation,
or partner's vasectomy. Examples of barrier method are male condom, diaphragm, or
cervical cap. FCBP must also agree to ongoing pregnancy testing. Men must practice
complete abstinence or agree to use a condom during sexual contact with FCBP while
participating in the study, during dose interruptions, and for at least 28 days
following discontinuation from the study, even if he has undergone a successful
vasectomy. All patients must be counseled at a minimum of every 28 days about
pregnancy precautions and risk of fetal exposure
- Men must agree to abstain from donating and semen or sperm while taking iberdomide,
during dose interruptions, and for at least 28 days after the last dose of
iberdomide. FCBP must agree not to donate eggs (ova, oocytes) for the purpose of
reproduction during this period
- All patients must agree to abstain from donating blood products while taking
iberdomide and for at least 28 days after the last dose of iberdomide
- Ability to understand and the willingness to sign a written informed consent
document. Legally authorized representatives may sign and give informed consent on
behalf of study subjects
- Willingness to adhere to the study visit schedule and other protocol requirements
and provide mandatory blood and bone marrow specimens for correlative research
- Willingness to return to the enrolling institution for follow-up
Exclusion Criteria:
- Patients who have active plasma cell leukemia, active amyloid light chain (AL)
(primary) amyloidosis, active polyneurophathy, organomegaly, endocrinopathy,
monoclonal gammopathy and skin changes (POEMS) syndrome (polyneuropathy,
organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, myeloma
protein, and skin changes), and Waldenstrom macroglobulinemia are ineligible
- If a patient develops recurrent/refractory (R/R) disease while receiving the most
recent line of therapy, there is no need for a washout period. Patients who develop
R/R disease while not on treatment must have received an investigational drug or
approved systemic anti-myeloma therapy (including systemic steroids) ≤ 14 days or 5
half-lives (whichever is shorter) prior to registration. This includes prior
treatment with a monoclonal antibody ≤ 30 days before receiving the first dose of a
study drug. The only exception is emergency use of a short course of systemic
corticosteroids (equivalent to, or less than: dexamethasone 40 mg/day for a maximum
of 4 days) before treatment
- Patients who have had prior anti-BCMA directed BsAb therapy exposure (prior
treatment with anti-BCMA directed antibody drug conjugate, or anti-BCMA-directed CAR
T cell therapy are permitted)
- Patients who have had prior treatment with a cereblon E3 ligase modulator, including
mezigdomide, iberdomide, and CFT7455 (all currently in clinical development)
- Patients who received plasmapheresis ≤ 7 days prior to registration
- Patients who received a prior allogeneic stem cell transplant. Autologous stem cell
transplantation (SCT) is allowed
- Patients who received a live or live-attenuated vaccine ≤ 30 days prior to
registration. Patients are allowed to receive a COVID-19 vaccine at any timepoint
during protocol treatment
- Systemic active infection requiring treatment
- Any unresolved toxicity ≥ grade 2 from previous treatment except for alopecia or
peripheral neuropathy up to grade 2
- Patients who have had any major surgery ≤ 4 weeks prior to registration
- Patients with uncontrolled intercurrent illness or any other significant
condition(s) that would make this protocol unreasonably hazardous
- Patients with evidence of active mucosal or internal bleeding
- Current unstable liver or biliary disease per investigator assessment defined by the
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or
gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease
(including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary
involvement of malignancy is acceptable if participant otherwise meets entry
criteria
- Patients with known immediate or delayed hypersensitivity reaction or idiosyncratic
reaction to drugs chemically related to teclistamab or iberdomide, or any of the
components of the study treatment
- Patients who are taking any anticancer therapy other than hormonal therapy (for
prostrate or breast cancer) and palliative radiotherapy (defined as radiation to ≤ 3
sites of active multiple myeloma)
- Patients who require immunosuppressive medications including, but not limited to,
systemic corticosteroids at doses exceeding 10 mg/day of prednisone or equivalent.
Use of immunosuppressive medications for the management of iberdomide-related
adverse events (AEs) or in subjects with contrast allergies is acceptable. In
addition, use of inhaled, topical, intranasal corticosteroids or local steroid
injection (e.g., intra-articular injection) is permitted. Temporary use of
corticosteroids for concurrent illnesses (e.g., food allergies, computed tomography
[CT] scan contrast hypersensitivity, pneumonia, etc.) are acceptable
- Patients who require medications that are strong inhibitors or inducers of CYP3A4/5
- Patients who are receiving any other investigational agents
- Patients with uncontrolled intercurrent illness or any other significant
condition(s) that would make participation in this protocol unreasonably hazardous
- Pregnant women are excluded from this study because iberdomide is a thalidomide
analog and thalidomide is a known human teratogen. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with iberdomide, breastfeeding should be discontinued if the mother is
treated with iberdomide. These potential risks may also apply to other agents used
in this study
- Patients who are unable or unwilling to undergo protocol required thromboembolism
prophylaxis are excluded
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Dana-Farber - Harvard Cancer Center LAO
Address:
City:
Boston
Zip:
02115
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ricardo D. Parrondo
Phone:
904-953-2000
Email:
parrondo.ricardo@mayo.edu
Investigator:
Last name:
Ricardo D. Parrondo
Email:
Principal Investigator
Start date:
July 8, 2025
Completion date:
September 16, 2026
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06465316
