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

Official title

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

Overview

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

• Biological OL-101 infusion
  OL-101 infusion will be administered to patients via IV infusion at the assigned dose.

Primary outcome measures

• Dose-limiting toxicity (DLT) [Time frame: Within 28 days post CAR-T infusion]
• Treatment emergent adverse event (TEAE) incidence and severity [Time frame: From aphresis till 1 year after CAR-T infusion or start of a new anti-cancer therapy, whichever is earlier]

Secondary outcome measures (12)

• Level of Immunogenicity [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Level of RCL [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Overall response rate (ORR) [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Minimal residual disease (MRD) negative rate [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Duration of response (DOR) [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Progression-free survival (PFS) [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Overall survival (OS) [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Cmax of OL-101 [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Tmax of OL-101 [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• AUC 0-28days of OL-101 [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Serum cytokines [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]
• Serum soluble circulating BCMA (sBCMA) [Time frame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first]

Eligibility criteria

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:

• Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
• 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:

• Hemoglobin ≥ 70 g/L
• Platelet count ≥ 50 × 10\^9/L
• Absolute lymphocyte count ≥ 0.3×10\^9/L
• Absolute neutrophil count ≥ 1.0 × 10\^9/L
• Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN)
• 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)
• Creatinine clearance ≥ 60 mL/min (calculated by Cockcroft-Gault equation).
• corrected serum calcium ≤12.5 mg/dL (≤3.1 mmol/L) or free ionized calcium ≤6.5 mg/dl (≤1.6 mmol/L)
• SpO2>92% on room air
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 3 centers

• Beijing Gobroad Boren Hospital — Beijing
• The Affiliated Hospital of Northwest University Xi'an No.3 Hospital — Xi’an
• The first affiliated hospital, College of Medicine, Zhejiang University — Hangzhou

Identifiers

NCT: NCT06644118 · OL-101-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗