An Evaluation of LY007 Cell Injection for r/r B-NHL

NCT06279611 | Recruiting Phase 1 DMC

• 1 other identifier: LY007C1101
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

An evaluation of LY007 cell injection for recurrent/refractory CD20 was positive Tolerability, safety, and efficacy of B-cell non-Hodgkin lymphoma in open, single-arm Phsea I Clinical research

Conditions

B-NHL

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose or clinically recommended dose

  No more than 1 out of 6 subjects experienced the highest dose of DLT. At least 6 subjects need to be evaluated at the MTD dose.

  Day0 to 2year

• Dose limiting toxicity

  Adverse events (AEs) that meet the following criteria and occur within 28 days after the subject receives LY007 cell injection reinfusion will be classified using the ASTCT 2018 standard for CRS and neurotoxicity, while the remaining AEs will be evaluated using the CTCAE 5.0 standard: 1. Any grade 4 or 5 AE related to LY007 cell injection after treatment, excluding no clinically significant laboratory test indicators; 2. Any grade 3 AE related to LY007 cell injection that does not improve to ≤ grade 2 within 7 days after treatment, excluding laboratory test indicators with no clinical significance; 3. Any grade 3 seizures that occur after treatment and cannot be relieved to ≤ grade 2 within 3 days; 4. Any ≥ level 3 autoimmune toxicity (excluding B cell dysgenesis) that occurs after treatment.

  Day0 to 2year

• Adverse Events , Serious Adverse Events , Adverse Events of Particular Concern

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0".

  Day0 to 2year

Secondary Outcomes (6)

• PK aspect

  Day0 to 2year

• PK aspect

  Day0 to 2year

• PD aspect

  Day0 to 2year

• therapeutic effect

  Day0 to 2year

• Anti LY007 antibody

  Day0 to 2year

Other Outcomes (1)

• Exploratory study endpoint

  Day0 to 2year

Study Arms (1)

LY007

EXPERIMENTAL

The CAR T cell preparation to be evaluated in this study is LY007, developed and produced by Shanghai Longyao Biotechnology Co., LTD Cell injection. LY007 cell injection is a chimeric antigen receptor targeting CD20 genetically modified using lentiviral vectors (CAR) Autologous T cells are CD20 CAR-T independently developed by Shanghai Longyao Biotechnology Co., LTD., in the CAR facility The independent co-stimulatory signal receptor OX40 was introduced to increase the proliferation and killing function of CAR-T cells. Table of CAR gene The frame comprises the following elements: (1) MSCVEF1α fusion promoter; (2) Single-chain antibody CD20 scFv targeting CD20; (3) CD8 junction and transmembrane region; (4) Intracellular region of 4-1BB; (5) CD3ζ intracellular region; (6) P2A self-shearing peptide; (7) Co-stimulated receptor OX40

Drug: LY007

Interventions

LY007 DRUG

FC and LY007 infusion

LY007

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years old (including 18 years old and 70 years old), regardless of gender;
• Can understand the study and have signed the informed consent;
• Expected survival time \> 3 months;
• The American Eastern Oncology Consortium (ECOG) score was 0-1;
• Cd20-positive B-NHL was confirmed cytologically or histologically according to WHO 2016 criteria These include diffuse large B-cell lymphomas (including histologically transformed forms) and transformed follicular lymphomas (TFL); (For the expression status of CD20, the histological diagnosis of CD20 has been clearly documented in the past Positive subjects (diagnosis within 3 months prior to screening); Subjects without prior records, Pathological specimens provided or collected by our hospital were diagnosed as CD20 positive; Not without a clear record For those who provide or collect specimens, the researchers and sponsors will decide whether to be included according to their medical records);
• For recurrent or refractory B-cell non-Hodgkin lymphoma, subjects must have at least been treated with anthracene Treatment with cyclodrugs and rituximab (or other CD20-targeting drugs), and have already received them At least two cycles of treatment; Refractory is defined as the best response to the most recent treatment regimen as disease progression, or the last treatment The optimal response of the regimen (at least 2 cycles) was stable disease with a duration of less than 6 months.
• Does not meet the criteria for autologous hematopoietic stem cell transplantation (auto-HSCT) or is unwilling to perform autologous transplantation Patients with recurrence or progression after blood stem cell transplantation or autologous hematopoietic stem cell transplantation;
• The venous access required for mononuclear cell collection can be established, and the hemoglobin is ≥70 g/L and neutral Granulocyte ≥ 1.0×109/L, platelet ≥50×109/L, a single nucleus can be performed by the investigator's judgment Cell collection;
• Evaluable lesions identified according to the 2014 Lugano efficacy evaluation criteria;
• Organ functions meet the following requirements:
• The investigator assessed sufficient bone marrow function to receive lymphocyte clearance chemotherapy;
• Serum creatinine ≤1.5× upper limit of normal (ULN) or creatinine clearance (Cockcroft and Gault) \> 30 mL/min/1.73 m2;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× ULN (ALT and AST in patients with liver metastasis ≤5×ULN);
• Total bilirubin ≤2.0 × ULN (for patients with Gilbert's syndrome or lymphoma invading the liver≤3 × ULN);
• Lung function: ≤CTCAE grade 1 dyspnea and oxygen saturation of basic finger pulse in indoor air environment Sum degree ≥92%;

You may not qualify if:

• Subjects who meet any of the following criteria are excluded from the study:
• Fully treated cervical carcinoma in situ and a history of other malignant tumors within 5 years prior to screening Adeno-papillary carcinoma, basal cell or squamous cell skin cancer, local front line after radical surgery Except adenocarcinoma and ductal carcinoma in situ after radical surgery;
• Hepatitis B surface antigen (HBsAg) positive, or Hepatitis B core antibody (HBcAb) positive and peripheral The blood HBV DNA titer was higher than the lower limit. Hepatitis C virus (HCV) antibody positive and HCV RNA titer was higher than the lower limit of detection. Positive for human immunodeficiency virus (HIV) antibodies; Serological test positive for syphilis;
• Any of the following unstable diseases (including but not limited to) have occurred in the 6 months prior to screening Stable angina pectoris; Cerebral ischemia or cerebral vascular accident; Myocardial infarction; Congestive heart failure (New York Heart Association \[NYHA\] classification ≥III); Severe cardiac arrhythmia requiring medical treatment Often; After heart angioplasty or coronary stent implantation or heart bypass surgery; mining History of deep vein thrombosis or pulmonary embolism within 6 months prior to cell collection;
• Lymphoma involving the central nervous system (CNS) only (subjects with secondary CNS lymphoma) Allow to be included);
• Previous or clinically significant central nervous system history or disease at the time of screening, such as epilepsy, epilepsy Seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, Organic syndrome or mental illness;
• Active autoimmune disease (including but not limited to systemic lupus erythematosus, dry disease) within 2 years Dryness syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, Hashimoto Thyroiditis, etc., except for hypothyroidism that can only be controlled by hormone replacement therapy);
• Active or uncontrolled infection requiring systemic treatment within 14 days prior to apheresis;
• There are active tuberculosis patients in the screening period;
• During the screening period, there are lymphoma lesions in the lung or gastrointestinal tract that are considered by investigators to be at risk of bleeding Of patients;
• Was receiving systemic steroid therapy prior to screening and was determined by the investigator to be prolonged during the study period Subjects treated with systemic steroids; Systemic treatment was used within 72 hours before cell transfusion Alcohol-treated subjects (except for inhalation or topical use);
• Pre-amperectomy CAR-T therapy (except previous CD19-targeted CAR-T therapy) Efficacy was evaluated as disease stable or at any time at 3 months after CD19 CAR-T reinfusion Efficacy evaluation for patients with disease progression) or other genetically modified T cell therapy;
• Received autologous stem cell transplantation within 6 weeks before anapheresis;
• Presence of grade ≥2 acute graft-versus-host disease (GVHD) requiring treatment within 4 weeks prior to anaphermology (Glucksberg standard) or generalized chronic GVHD (Seattle Standard) or by researchers Who may need anti-GVHD therapy during the trial;
• Treatment with alenzumab 6 months before monocyst, or fludarabine or Fludarabine within 3 months before monocyst Cladobine treatment;

Sponsors & Collaborators

• Shanghai Longyao Biotechnology Inc., Ltd.: lead
• The First Affiliated Hospital with Nanjing Medical University: collaborator
• Ruijin Hospital: collaborator

Study Sites (1)

Ruijin hospital

Shanghai, Shanghai Municipality, China

RECRUITING

Study Officials

• Zhao Weili, MD

  Ruijin Hospital, Shanghai Jiaotong University School of Medicine Recruiting Shanghai, Shanghai, China, 200025

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhao Weili, MD

CONTACT

+862164370045; zwl_trial@163.com

Yan Zixun, MD

CONTACT

+8613482056727; yanzixun125@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2024
• First Posted: February 28, 2024
• Study Start: December 25, 2021
• Primary Completion: August 31, 2024
• Study Completion (Estimated): May 31, 2026
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

CN (1)