Trial Title:
External Beam Radiation Therapy in Combination With Talquetamab for the Treatment of Multiple Myeloma Patients With Extramedullary Disease
NCT ID:
NCT06572605
Condition:
Extramedullary Disease in Multiple Myeloma
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Antibodies
Immunoglobulins
Antibodies, Bispecific
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet 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 collection of blood samples
Arm group label:
Treatment (EDM-EBRT, talquetamab)
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
Arm group label:
Treatment (EDM-EBRT, talquetamab)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Treatment (EDM-EBRT, talquetamab)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT and/or PET/CT
Arm group label:
Treatment (EDM-EBRT, talquetamab)
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:
Other
Intervention name:
Electronic Health Record Review
Description:
Ancillary studies
Arm group label:
Treatment (EDM-EBRT, talquetamab)
Intervention type:
Radiation
Intervention name:
External Beam Radiation Therapy
Description:
Undergo EMD-EBRT
Arm group label:
Treatment (EDM-EBRT, talquetamab)
Other name:
Definitive Radiation Therapy
Other name:
EBRT
Other name:
External Beam Radiation
Other name:
External Beam Radiotherapy
Other name:
External Beam Radiotherapy (conventional)
Other name:
External Beam RT
Other name:
external radiation
Other name:
External Radiation Therapy
Other name:
external-beam radiation
Other name:
Radiation, External Beam
Other name:
Teleradiotherapy
Other name:
Teletherapy
Other name:
Teletherapy Radiation
Intervention type:
Procedure
Intervention name:
Image Guided Biopsy
Description:
Undergo image-guided EMD biopsy
Arm group label:
Treatment (EDM-EBRT, talquetamab)
Other name:
Image-Guided Biopsy
Other name:
Imaging for Biopsy
Other name:
Imaging Guided Biopsy
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Treatment (EDM-EBRT, talquetamab)
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:
Biological
Intervention name:
Talquetamab
Description:
Given SC
Arm group label:
Treatment (EDM-EBRT, talquetamab)
Other name:
Anti-CD3/Anti-GPRC5D Bispecific Monoclonal Antibody JNJ-64407564
Other name:
GPRC5D x CD3 Bispecific Antibody JNJ-64407564
Other name:
GPRC5D x CD3 DuoBody Antibody JNJ-64407564
Other name:
GPRC5D/CD3 DuoBody Antibody JNJ-64407564
Other name:
Humanized GPRC5D x CD3 DuoBody Antibody JNJ-64407564
Other name:
JNJ 64407564
Other name:
JNJ-64407564
Other name:
JNJ64407564
Other name:
Talquetamab-tgvs
Summary:
This phase I/II trial tests the safety and effectiveness of extramedullary disease
(EMD)-directed external beam radiation therapy (EBRT) in combination with talquetamab for
the treatment of multiple myeloma patients with extramedullary disease. Extramedullary
disease in multiple myeloma involves the infiltration of organs and soft tissues by
malignant plasma cells and has proven difficult to treat. Radiation therapy uses high
energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink cancers.
EBRT is a type of radiation therapy that delivers high-energy beams to the cancer from
outside of the body. In this trial, the EBRT will be directed to a site of extramedullary
disease. Talquetamab is a monoclonal antibody that may interfere with the ability of
cancer cells to grow and spread. 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). Combining EMD-directed EBRT with talquetamab may be safe, tolerable,
and/or effective in treating multiple myeloma patients with extramedullary disease.
Detailed description:
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of single-field, palliative, extramedullary
disease (EMD)-directed external beam radiotherapy (EMD-EBRT) in combination with
talquetamab as assessed by incidence of adverse events (AEs) throughout the trial and
unexpected toxicities (UTs) during step-up and cycle 1. (Phase 1b) II. To evaluate the
systemic anti-tumor activity/preliminary efficacy of EMD-EBRT in combination with
talquetamab as assessed by EMD-modified overall response rate (ORR). (Phase 2)
SECONDARY OBJECTIVE:
I. To additionally evaluate efficacy through International Myeloma Working Group (IMWG)
overall response rate (ORR), duration of response (DOR), progression-free survival (PFS),
and overall survival (OS).
EXPLORATORY OBJECTIVES:
I. To assess the impact of EMD-EBRT combined with talquetamab on peripheral blood immune
cell populations.
II. To assess the spatial transcriptomic changes in the medullary and extramedullary
tumor microenvironment in response to EMD-EBRT combined with talquetamab.
OUTLINE:
STEP-UP PERIOD: Patients undergo EMD-EBRT once daily (QD) for 5 treatment fractions on
weekdays (Monday to Friday), and receive talquetamab subcutaneously (SC) starting after
the first fraction of EMD-EBRT and continuing every 2-4 days for up to 3 step-up doses in
the absence of unacceptable toxicity.
SUBSEQUENT TREATMENT: Starting 2-7 days after step-up dose 3, patients receive
talquetamab SC on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to a
maximum of 13 total cycles in the absence of disease progression or unacceptable
toxicity.
Patients also undergo computed tomography (CT) and/or positron emission tomography
(PET)/CT and collection of blood samples throughout the trial and undergo image-guided
EMD biopsy at screening and on study. Patients undergo bone marrow biopsy/aspiration at
screening and optionally at end of treatment.
After completion of study treatment, patients are followed up every 28 days for up to 12
months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Documented informed consent of the participant and/or legally authorized
representative
- Assent, when appropriate, will be obtained per institutional guidelines
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- If unavailable, exceptions may be granted with study principal investigator
(PI) approval
- Age: ≥ 18 years
- Karnofsky performance status (KPS) ≥ 60%
- Diagnosis of multiple myeloma with extramedullary disease (EMD). EMD is defined as
soft-tissue plasmacytomas NOT arising from skeletal lesions (i.e., the EMD is not
contiguous with any bone/bony lesion)
- Measurable systemic disease defined as serum M-spike ≥ 0.5 g/dl, 24-hour urine
M-spike ≥ 200 mg/24 hours (hr), involved serum free light chain (FLC) ≥ 10 mg/dl
with abnormal FLC ratio, and/or a non-target plasmacytoma ≥ 2 cm in a single
diameter (NOTE: Non-target plasmacytoma must not be included in the EMD-EBRT field)
- At least one site of EMD must have an indication for palliative radiation per the
treating clinicians (e.g., including but not limited to pain, asymmetry, discomfort,
threatening to vital structure, etc.)
- Target EMD site must be encompassed by one radiation field per treating radiation
oncologist
- Subject must have received an immunomodulatory agent, a proteasome inhibitor, and an
anti-CD38 antibody
- Fully recovered from the acute non-hematologic toxic effects (except alopecia) to ≤
grade 1 to prior anti-cancer therapy
- Prior antitumor therapy must have been completed prior to enrollment as follows:
- ≥ 2 weeks for prior external beam radiotherapy (XRT) to non-target site
- ≥ 21 days for cytotoxic chemotherapy (systemic or intrathecal)
- ≥ 28 days for prior adoptive cell therapy or T-cell redirecting therapies
- ≥ 4 weeks or 5 half-lives (whichever is shorter) for other myeloma therapies
- Absolute neutrophil count (ANC) ≥ 1,000/mm^3 (prior growth factor support is
permitted but must be without support for 7 days for granulocyte colony-stimulating
factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF] and for
14 days for pegylated GCSF before the laboratory test)
- Two repeat tests are allowed. If the repeat test satisfies criteria, the
participant may enroll provided all other criteria are met
- Platelets ≥ 50,000/mm^3
- NOTE: No transfusion support or thrombopoietin receptor agonist within 7 days
before laboratory test
- Two repeat tests are allowed. If the repeat test satisfies criteria, the
participant may enroll provided all other criteria are met
- Hemoglobin ≥ 8g/dL
- NOTE: No transfusion support or erythropoietin use within 7 days before the
laboratory test
- Two repeat tests are allowed. If the repeat test satisfies criteria, the
participant may enroll provided all other criteria are met
- Total bilirubin ≤ 2.0 X upper limit of normal (ULN) (unless has congenital
bilirubinemia such as Gilbert's disease, in which case ≤ 1.5 × ULN is required)
- Two repeat tests are allowed. If the repeat test satisfies criteria, the
participant may enroll provided all other criteria are met
- Aspartate aminotransferase (AST) ≤ 2.5 x ULN
- Two repeat tests are allowed. If the repeat test satisfies criteria, the
participant may enroll provided all other criteria are met
- Alanine aminotransferase (ALT) ≤ 2.5 x ULN
- Two repeat tests are allowed. If the repeat test satisfies criteria, the
participant may enroll provided all other criteria are met
- Creatinine clearance of ≥ 30 mL/min per 24 hour urine test or the Cockcroft-Gault
formula
- Two repeat tests are allowed. If the repeat test satisfies criteria, the
participant may enroll provided all other criteria are met
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
- If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required
- Two repeat tests are allowed. If the repeat test satisfies criteria, the
participant may enroll provided all other criteria are met
- Agreement by females and males of childbearing potential to use an effective method
of birth control or abstain from heterosexual activity for the course of the study
through at least 6 months after the last dose of talquetamab
- Childbearing potential defined as not being surgically sterilized (men and
women) or have not been free from menses for > 1 year (women only)
Exclusion Criteria:
- Prior irradiation to target EMD site or field
- Prior GPRC5D therapy
- Prior radiopharmaceutical therapy
- Patients who have received previous radiation to > 25% of their bone marrow
- Prior allogeneic hematopoietic cell transplantation within the past 6 months or
prior autologous hematopoietic cell transplantation within the past 12 weeks
- A maximum cumulative dose of corticosteroids of ≥ 140 mg of prednisone or equivalent
within 14-day period before the first dose of study drug (does not include
pre-treatment medications)
- Major surgery within 2 weeks prior to the start of administration of study
treatment, or will not have fully recovered from surgery, or has major surgery
planned during the time the participant is expected to be treated in the study, or
within 2 weeks after administration of the last dose of study treatment
- Note: Participants with planned surgical procedures to be conducted under local
anesthesia may participate. Kyphoplasty or vertebroplasty are not considered
major surgery. If there is a question whether a procedure is considered a major
surgery, the investigator must consult with the appropriate representative at
Janssen and resolve any issues before enrolling a participant in the study
- Ongoing or active infection
- Severe persistent asthma or severe chronic obstructive pulmonary disease (COPD)
- Presence of the following cardiac conditions:
- New York Heart Association stage III or IV congestive heart failure
- Myocardial infarction or coronary artery bypass graft ≤ 6 months prior to
randomization
- Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram
(ECG) abnormalities
- 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
- Any of the following:
- Hepatitis B infection (i.e., hepatitis B virus surface antigen [HBsAg] or
hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] positive). In the event the
infection status is unclear, quantitative viral levels are necessary to
determine the infection status
- Active hepatitis C infection as measured by positive hepatitis C virus
[HCV]-ribonucleic acid [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 for at least
12 weeks following the completion of therapy, the participant is eligible for
the study
- Plasma cell leukemia (> 20% circulating plasma cells and/or > 2.0 x 10^9/L plasma
cells) at the time of screening, Waldenström's macroglobulinemia, POEMS syndrome
(polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or
primary amyloid light chain amyloidosis
- Known active central nervous system (CNS) involvement or exhibits clinical signs of
meningeal involvement of multiple myeloma. If either is suspected, negative whole
brain MRI and lumbar cytology are required
- Other active malignancy. 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
- Stroke or seizure within 6 months prior to enrollment
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to study agent
- If HIV positive, any of the following:
- Detectable viral load at screening
- CD4+ T cell count ≤ 300
- AIDS-defining opportunistic infection within 6 months of screening
- Changes in highly active antiretroviral therapy (HAART) due to
resistance/progression that occurred within 3 months prior to screening
- Changes in HAART due to toxicity within 4 weeks prior to screening
- Females only: Pregnant or breastfeeding
- Any other condition that would, in the Investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Contact:
Last name:
Scott R. Goldsmith
Phone:
626-218-2405
Email:
sgoldsmith@coh.org
Investigator:
Last name:
Scott R. Goldsmith
Email:
Principal Investigator
Start date:
December 15, 2024
Completion date:
June 30, 2028
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06572605
