A Phase 1b/2 Study of Talquetamab Plus Concomitant Priming Radiotherapy in Multiple Myeloma With Extramedullary Disease
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.
• 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)