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

Phase 1

Recruiting

• Conditions: Multiple Myeloma
• Interventions: Biological: OL-101 infusion

• Registration Number: NCT06644118
• Lead Sponsor: Zhejiang University

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.

Study Timeline

• Study First Submitted: 2024-09-28
• Study First Submitted QC: 2024-10-14
• Study First Posted: 2024-10-16
• Study Start: 2024-10-23
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-06
• Last Update Posted: 2024-11-08
• Primary Completion: 2027-10
• Study Completion: 2028-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 58

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
OL-101 infusion	OL-101 infusion	This arm provides CAR-T treatment at the dose the patient is assigned to.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
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
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
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.
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.
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.

Trial Locations

Locations (3)

Beijing Gobroad Boren Hospital; 🇨🇳 Beijing, Beijing, China

The Affiliated Hospital of Northwest University Xi'an No.3 Hospital; 🇨🇳 Xi'an, Shanxi, China

The first affiliated hospital, College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China