Safety and Efficacy of RN9101 in the Treatment of Relapsed/Refractory Multiple Myeloma

Inclusion Criteria:

• Subjects must meet all of the following criteria to be enrolled in this study:

  1. Age ≥18 years, either sex;
  2. Diagnosis of multiple myeloma (MM) according to IMWG response criteria, with BCMA target antigen expression on MM cells confirmed by flow cytometry or bone marrow pathology and immunohistochemistry;
  3. Received at least 2 prior lines of anti-multiple myeloma therapy, with each line containing at least one complete treatment cycle, and documented disease progression during or after the most recent anti-myeloma therapy based on assessment data;

  4. Measurable disease at screening, defined as meeting at least one of the following criteria:

     1. Serum M-protein ≥ 0.5 g/dL;
     2. Urine M-protein level ≥ 200 mg/24 h;
     3. Involved serum free light chain ≥ 10 mg/dL with abnormal serum free light chain κ/λ ratio;
     4. Clinical relapse: a. New bone lesions or soft tissue plasmacytomas (excluding osteoporotic fractures); b. Definite increase in existing plasmacytomas or bone lesions (sum of the products of perpendicular diameters [SPD] of measurable lesions increased by ≥50% with an absolute increase of ≥1 cm);
  5. ECOG performance status of 0-2, with an estimated life expectancy of ≥3 months;

  6. Bone marrow function test results (at screening or within 2 months prior to screening) meeting the following conditions:

     1. Hemoglobin ≥ 6 g/dL (no red blood cell transfusion within 1 week prior to screening), with recombinant human erythropoietin permitted; for patients meeting the hemoglobin ≥ 6 g/dL enrollment criterion, red blood cell transfusions may be allowed to maintain hemoglobin ≥ 6 g/dL;
     2. Absolute neutrophil count (ANC) ≥ 600/μL (no granulocyte colony-stimulating factor [G-CSF] used within 1 week prior to screening, or no pegylated G-CSF used within 2 weeks prior to screening);
     3. Platelet count ≥ 50,000/μL;
     4. Lymphocyte count ≥ 500/μL;
     5. Absolute CD3-positive T-cell count ≥ 150/μL;
  7. Normal renal function during screening or within 2 months prior to screening: creatinine clearance (CrCl) (calculated by the Cockcroft-Gault formula) ≥ 45 mL/min;

  8. Hepatic function during screening or within 2 months prior to screening meeting the following conditions:

     1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal (ULN);
     2. Total bilirubin (TBIL) and alkaline phosphatase (AKP or ALP) ≤ 2.0 × ULN (except for congenital hyperbilirubinemia, such as Gilbert's syndrome, where direct bilirubin may be ≤ 1.5 × ULN);
     3. Albumin ≥ 3 g/dL;

  9. Cardiac function during screening or within 2 months prior to screening meeting the following conditions:

     1. Left ventricular ejection fraction (LVEF) ≥ 40% (assessed by echocardiography or MUGA scan);
     2. No clinically significant pericardial effusion;
     3. No clinically significant electrocardiogram abnormalities;

  10. Pulmonary function during screening or within 2 months prior to screening meeting the following conditions:

      1. Oxygen saturation ≥ 90%;
      2. No clinically significant pleural effusion;
  11. For females of childbearing potential, a negative pregnancy test at screening and prior to dosing, and not currently breastfeeding;
  12. Males and females of childbearing potential must agree to use effective contraception from the date of informed consent signing until 1 year after the end of study treatment;
  13. Males and females of childbearing potential must agree not to donate gametes (including sperm or ova) from the date of informed consent signing until 1 year after the end of study treatment;
  14. The subject or their legally authorized representative has signed the Informed Consent Form (ICF), indicating understanding of the study objectives and procedures, and voluntary participation in this study.

Exclusion Criteria:

• Subjects meeting any of the following criteria will be excluded from the study:

  1. Received other anti-tumor therapy during the screening period (as determined primarily by the investigator):

     1. Received targeted therapy, epigenetic therapy, other investigational drug therapy, or treatment involving invasive investigational medical devices within 5 half-lives;
     2. Received systemic immunologic or non-immunologic therapy within 1 week;
     3. Received cytotoxic therapy within 1 week;
     4. Received proteasome inhibitor and immunomodulatory therapy within 2 weeks;
     5. Received radiotherapy within 4 weeks (except if the radiation field involves ≤5% of bone marrow reserve, in which case there is no restriction on the time since completion of radiotherapy, and the subject may still be enrolled);
  2. Received allogeneic hematopoietic stem cell transplantation within 6 months prior to dosing, or autologous hematopoietic stem cell transplantation within 3 months prior to dosing;
  3. History of malignancy other than multiple myeloma prior to screening, except for the following: malignancies treated with curative intent and with no known active disease for ≥2 years prior to enrollment; adequately treated non-melanoma skin cancer with no current evidence of disease;
  4. Previously received any therapy utilizing vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped virus;
  5. Presence of severe and uncontrolled infection during screening (including bacterial, viral, fungal, etc.);
  6. Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), with peripheral blood hepatitis B virus (HBV) DNA titer above the normal range detected within 6 months prior to infusion; positive hepatitis C virus (HCV) antibody with peripheral blood HCV RNA titer above the normal range; positive human immunodeficiency virus (HIV) antibody; positive syphilis test;

  7. Symptomatic heart failure or other cardiac diseases, such as severe arrhythmias:

     1. New York Heart Association (NYHA) Class III or IV congestive heart failure;
     2. Myocardial infarction within 6 months prior to informed consent signing, or prior coronary artery bypass grafting (CABG) or coronary artery stent implantation;
     3. Clinically significant ventricular arrhythmias or history of unexplained syncope (excluding vasovagal or dehydration-induced syncope);
     4. History of severe non-ischemic cardiomyopathy;

  8. Other clinically significant diseases, including:

     1. Primary immunodeficiency;
     2. Stroke or seizure within 6 months prior to screening;
     3. Definite clinical evidence of dementia or altered mental status;
     4. Parkinson's disease, parkinsonian movement disorders, or relevant history;
  9. Received surgery within 2 weeks prior to dosing, or planned surgery within 2 weeks after dosing (except for local anesthesia procedures);
  10. Received live attenuated vaccines within 1 month prior to dosing;
  11. Known severe allergic reaction to RN9101 or any of its formulation components;
  12. Known severe allergic reaction to tocilizumab;
  13. Patients unsuitable for intravenous infusion;
  14. Other conditions deemed by the investigator as rendering the subject unsuitable for participation in this study.