QLS4131 for Relapsed/Refractory Multiple Myeloma With Extramedullary Disease

Prior treatment

• Previous treatment with simultaneous BCMA and GPRC5D targeting therapies, including separate treatment targeting BCMA and GPRC5D, or treatment with dual-target BCMA and GPRC5D therapies.
• Radiotherapy: In principle, participants should not have received radiotherapy within 3 months before enrollment. If the lesion has previously received radiotherapy, radiographic evidence of clear progression after radiotherapy is required before it can be considered a baseline target lesion.
• Major surgery within 4 weeks before the first administration of study drug, or planned major surgery during the study period.
• Concurrent other malignancies; or serious concomitant diseases that, in the investigator's assessment, seriously threaten participant safety or affect completion of the study.

Other illness

• Diagnosis of smoldering multiple myeloma (SMM), monoclonal gammopathy of undetermined significance (MGUS), Waldenström macroglobulinemia, POEMS syndrome, amyloidosis, or primary/secondary plasma cell leukemia.
• Severe and/or uncontrolled cardiac disease.
• Active infection, including HIV infection, active hepatitis B (HBV-DNA positive), active hepatitis C (HCV-RNA positive), active or latent syphilis, active tuberculosis, or other active infections considered unsuitable by the investigator.
• History of severe allergy or hypersensitivity to study drug components.
• Any other conditions that, in the investigator's judgment, make the participant unsuitable for enrollment.

Other

• Central nervous system involvement or clinical evidence of meningeal involvement.
• Pregnant or breastfeeding women.

• 1\. Participants who are aware of and voluntarily sign the informed consent form (ICF), aged ≥18 years at the time of signing the ICF; male or female.
• 2\. ECOG performance status of 0-2. 3. Diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) criteria, and meeting the following criteria:
• Received at least 1 line of systemic anti-myeloma therapy, previously exposed to proteasome inhibitors (PI), immunomodulatory drugs (IMiD), and anti-CD38 monoclonal antibodies, and refractory to the most recent line of therapy or progressed within the specified time after completion of the most recent line of therapy;
• Extramedullary disease identified by imaging examination, including the following two categories:
  • True extramedullary disease (true EMD): soft tissue or organ plasmacytoma not contiguous with bone, with at least one lesion measuring ≥2 cm in the longest diameter;
  • Paraskeletal disease (PSD): lesions formed by extension of bone lesions through the cortical bone into adjacent soft tissue, with at least one lesion measuring ≥5 cm in the longest diameter, or more than 2 paraskeletal lesions measuring ≥2 cm in the longest diameter.
  • 4\. Participants who have previously received CAR-T cell therapy or bispecific antibody therapy are allowed. For participants who have previously received BCMA- or GPRC5D-targeted therapy, prior targeted therapy must involve only one of the targets, BCMA or GPRC5D. The interval from CAR-T cell infusion to the first administration of study drug must be ≥3 months, and the interval from the last dose of bispecific antibody to the first administration of study drug must be ≥28 days.
  • 5\. Participants without measurable hematologic disease are allowed to enroll. Measurable hematologic disease is defined as meeting any one or more of the following criteria:
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  • Serum M protein level ≥1.0 g/dL;
  • Urine M protein level ≥200 mg/24 hours;
  • Serum free light chain level ≥10 mg/dL with an abnormal serum free light chain ratio.
  • 6\. Adequate organ function. 7. Participants must voluntarily participate and be able to complete the study procedures and follow-up examinations.