External Beam Radiation Therapy in Combination With Talquetamab for the Treatment of Multiple Myeloma Patients With Extramedullary Disease

NCT06572605 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 23931NCI-2024-06707P30CA033572
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Extramedullary Disease in Multiple Myeloma; Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (phase 1b)

  Toxicity will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome. Toxicity information recorded in each patient will include the type, severity, and the probable association with the study regimen. Tabular and graphical summaries will be used to represent the observed incidence by severity and type of toxicity.

  From start of protocol therapy until cycle 1 day 28

• Extramedullary disease (EMD)-modified overall response rate (ORR) (phase 2)

  EMD-modified ORR will be defined as the proportion of patients meeting the criteria for partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR). Disease response will be evaluated per International Myeloma Working Group (IMWG) response criteria and Response Criteria for EMD. Clopper-Pearson 95% confidence intervals will be calculated for these estimates.

  Up to 12 months

Secondary Outcomes (5)

• Progression-free survival

  From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 12 months

• Overall survival

  From first day of treatment to time of death due to any cause, assessed up to 12 months

• Duration of response

  From first response documented until disease progression, assessed up to 12 months

• Clinical benefit rate

  Up to 12 months

• Incidence of adverse events

  Up to 12 months

Study Arms (1)

Treatment (EDM-EBRT, talquetamab)

EXPERIMENTAL

STEP-UP PERIOD: Patients undergo EMD-EBRT QD for 5 treatment fractions on weekdays (Monday to Friday), and receive talquetamab 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 CT and/or 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.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Other: Electronic Health Record Review; Radiation: External Beam Radiation Therapy; Procedure: Image Guided Biopsy; Procedure: Positron Emission Tomography; Biological: Talquetamab

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (EDM-EBRT, talquetamab)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (EDM-EBRT, talquetamab)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (EDM-EBRT, talquetamab)

Computed Tomography PROCEDURE

Undergo CT and/or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (EDM-EBRT, talquetamab)

Electronic Health Record Review OTHER

Ancillary studies

Treatment (EDM-EBRT, talquetamab)

External Beam Radiation Therapy RADIATION

Undergo EMD-EBRT

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam Radiotherapy (conventional), External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

Treatment (EDM-EBRT, talquetamab)

Image Guided Biopsy PROCEDURE

Undergo image-guided EMD biopsy

Also known as: Image-Guided Biopsy, Imaging for Biopsy, Imaging Guided Biopsy

Treatment (EDM-EBRT, talquetamab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (EDM-EBRT, talquetamab)

Talquetamab BIOLOGICAL

Given SC

Also known as: Anti-CD3/Anti-GPRC5D Bispecific Monoclonal Antibody JNJ-64407564, GPRC5D x CD3 Bispecific Antibody JNJ-64407564, GPRC5D x CD3 DuoBody Antibody JNJ-64407564, GPRC5D/CD3 DuoBody Antibody JNJ-64407564, Humanized GPRC5D x CD3 DuoBody Antibody JNJ-64407564, JNJ 64407564, JNJ-64407564, JNJ64407564, Talquetamab-tgvs

Treatment (EDM-EBRT, talquetamab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Specimen Handling; Biopsy; Congresses as Topic; Radiation; Image-Guided Biopsy; X-Rays; Magnetic Resonance Spectroscopy; talquetamab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Organizations; Health Care Economics and Organizations; Physical Phenomena; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Radiation, Ionizing; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Scott R Goldsmith

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 27, 2024
• Study Start: August 29, 2025
• Primary Completion (Estimated): January 18, 2030
• Study Completion (Estimated): January 18, 2030
• Last Updated: September 19, 2025

Record last verified: 2025-09

Locations

US (1)