Clinical trial NCT06644118: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: OL-101
Multiple myeloma
Phase 1
single arm
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Overland Therapeutics
First posted: 2024-10-16
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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:

  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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Within 28 days post CAR-T infusion
measure: Treatment emergent adverse event (TEAE) incidence and severity
timeFrame: From aphresis till 1 year after CAR-T infusion or start of a new anti-cancer therapy, whichever is earlier
Secondary outcomes:
measure: Level of Immunogenicity
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
measure: Level of RCL
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
measure: Overall response rate (ORR)
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
measure: Minimal residual disease (MRD) negative rate
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
measure: Duration of response (DOR)
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
measure: Progression-free survival (PFS)
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
measure: Overall survival (OS)
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
measure: Cmax of OL-101
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
measure: Tmax of OL-101
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
measure: AUC 0-28days of OL-101
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
measure: Serum cytokines
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
measure: Serum soluble circulating BCMA (sBCMA)
timeFrame: Baseline until 2 years after CAR-T infusion or withdrawn from the study, whichever comes first
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Gobroad Boren Hospital
state: Beijing
city: Xi'an
country: China
facility: The Affiliated Hospital of Northwest University Xi'an No.3 Hospital
state: Shanxi
city: Hangzhou
country: China
facility: The first affiliated hospital, College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
References: