Multiple Myeloma
Conditions
Keywords
OL-101, Multiple myeloma, Phase 1, single arm
Brief summary
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).
Detailed description
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.
Interventions
BIOLOGICALOL-101 infusion
OL-101 infusion will be administered to patients via IV infusion at the assigned dose.
Sponsors
Overland Therapeutics
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-limiting toxicity (DLT) | Within 28 days post CAR-T infusion | Adverse events will be assessed based on the CTCAE 5.0 |
| Treatment emergent adverse event (TEAE) incidence and severity | From aphresis till 1 year after CAR-T infusion or start of a new anti-cancer therapy, whichever is earlier | Adverse events will be assessed based on the CTCAE 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Level of Immunogenicity | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | To assess the presence of antibodies to OL-101 (ADA) |
| Minimal residual disease (MRD) negative rate | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | Proportion of subjects with MRD negative status as defined by the IMWG response criteria |
| Duration of response (DOR) | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | The time from the initial response to therapy until the disease progression or relapse. |
| Progression-free survival (PFS) | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | The time from CAR-T cell infusion to the first assessment of disease progression or death from any cause. |
| Overall survival (OS) | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | The time from CAR-T cell infusion to death from any cause. |
| Level of RCL | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | To determine whether Replication Competent Lentivirus (RCL) is present in patient that receive OL-101 |
| Tmax of OL-101 | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | The time of the maximum concentration will be measured to assess OL-101 in vivo expansion and persistence. |
| AUC 0-28days of OL-101 | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | Area under the curve will be measured to assess OL-101 in vivo expansion and persistence. |
| Serum cytokines | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | The levels of cytokines will be measured, such as IL-6 and ferritin. |
| Serum soluble circulating BCMA (sBCMA) | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | Serum soluble circulating BCMA will be measured to explore its potential relationship to response or resistance. |
| Cmax of OL-101 | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | The maximum concentration of the CAR-T cells will be measured to assess OL-101 in vivo expansion and persistence. |
| Overall response rate (ORR) | Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first | Proportion of subjects with PR or above |
Countries
China
Contacts
Primary ContactHe Huang, MD, PhD
Backup ContactYongxian Hu, MD, PhD
Outcome results
None listed