A Study of OL-101 Injection in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

A Pilot Clinical Study of OL-101 Injection in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

This clinical trial aims to characterize the safety of OL-101 and establish the recommended dose for future research and to evaluate the efficacy of OL-101 (Dose expansion).

This study will evaluate the safety and efficacy of OL-101, a chimeric antigen receptor T cell (CAR-T) therapy directed against B-Cell Maturation Antigen (BCMA) and G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D). This study is a single-arm, open-label, early exploratory clinical trial, conducted in two phases: dose escalation and dose expansion in adults with multiple myeloma. The trial begins with the dose-escalation phase that focus on safety and tolerability, with interval assessments for potential dose escalation or de-escalation. Recommended dose will be selected at the completion of the dose escalation stage in the dose expansion stage. The study aims to assess safety, pharmacokinetic/pharmacodynamic profiles, and efficacy.

Inclusion Criteria:

• Documented diagnosis of multiple myeloma according to the 2014 IMWG diagnostic criteria

• Relapsed/refractory multiple myeloma as defined by:

  1) Received at least 3 prior lines of MM treatment (must include a PI, an IMiD, and an anti-CD38 antibody).

  2）Disease progression within 12 months of the most recent anti-MM therapy; or disease progression within the past 6 months and subsequently lack response to the most recent line of therapy.

• Measurable disease at screening as defined by any of the following:

  1. Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
  2. Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.

• Positive expression of either BCMA or GPRC5D on bone marrow plasma cells; must be GPRC5D expression positive if previously received BCMA targeted therapy

• ECOG 0-1

• Expected life expectancy exceeds 12 weeks

• Adequate bone marrow reserve or organ function meeting the following criteria:

  1. Hemoglobin ≥ 70 g/L
  2. Platelet count ≥ 50 × 10^9/L
  3. Absolute lymphocyte count ≥ 0.3×10^9/L
  4. Absolute neutrophil count ≥ 1.0 × 10^9/L
  5. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN)
  6. Total bilirubin ≤ 2 times ULN; except in subjects with congenital bilirubinemia (such as Gilbert syndrome, in which case the direct bilirubin ≤1.5 × ULN is required)
  7. Creatinine clearance ≥ 60 mL/min (calculated by Cockcroft-Gault equation).
  8. corrected serum calcium ≤12.5 mg/dL (≤3.1 mmol/L) or free ionized calcium ≤6.5 mg/dl (≤1.6 mmol/L)
  9. SpO2>92% on room air
  10. Left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram; no clinically meaningful pericardial effusion by ultrasound

Exclusion Criteria:

• Solitary plasmacytoma
• Known active central nervous system (CNS) involvement or exhibits clinical signs of CNS involvement of multiple myeloma.
• Received allogeneic stem cell transplant; received autologous stem cell transplant within 12 weeks before screening
• Active second primary malignant tumor, exclude the following: cured non- melanoma skin cancer, non-metastatic prostate cancer, cervical carcinoma in situ, ductal or lobular carcinoma in situ of the breast
• Any other significant medical disease, abnormality, or condition that, in the investigator judgment, may make the patient unsuitable for participation in the study or put the patient at risk.
• Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or primary AL amyloidosis.