A Clinical Study on LM103 for the Treatment of Advanced Solid Tumors

Study Overview
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Brief Summary
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This study is an open exploratory clinical study to evaluate the safety, tolerance, immune response, and initial efficacy of autologous tumor infiltrating lymphocyte LM103 injection in advanced solid tumor patients . The research treatment includes fludarabine and cyclophosphamide, autologous tumor infiltrating lymphocytes (TILs) infusion, and IL-2 therapy.

Official Title
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An Exploratory Clinical Study Evaluating the Safety, Tolerance, Immune Response, and Initial Efficacy of Autologous Tumor Infiltrating Lymphocytes (TILs) LM103 Injection in Patients With Advanced Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Biological: LM103


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The expected survival time is not less than 3 months. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-1. Patients with advanced solid tumors confirmed by histology or cytology: advanced Melanoma, cervical cancer/ovarian cancer, head and neck squamous cell cancer, non-small cell lung cancer, esophageal cancer and other solid tumors that have failed standard treatment regimens, cannot tolerate standard treatment, refuse or do not have standard treatment regimens available. The patient has lesions that can be used for surgical resection (>1.5 cm3) or biopsy puncture (no less than 6 lesions) for TILs collection. At least one measurable lesion as the target lesion after collecting tumor tissue from the patient (RECIST v1.1 criteria). Laboratory tests results during the screening period indicate that the subjects have sufficient organ function. Exclusion Criteria: Have a medical history of other malignant tumors other than the disease under study in the past 5 years, except for malignant tumors that can be expected to recover after treatment (including but not limited to thyroid cancer, cervical Carcinoma in situ, basal or squamous cell skin cancer or Ductal carcinoma in situ of the breast treated by radical surgery). LM103 received systematic Sex therapy of antineoplastic drugs (including chemotherapy, small molecule targeted drug therapy, Hormone replacement therapy, etc.), or local antineoplastic therapy (such as radiotherapy, palliative radiotherapy for bone metastases>2 weeks before the start of the study and intracranial stereotactic radiotherapy or resection of a single brain metastasis>3 weeks before the start of the study were acceptable) within 4 weeks before LM103 infusion; Or received clinical investigational drugs or equipment treatment. Adverse reactions caused by previous treatment have not recovered to CTCAE (version 5.0) level 1 or below (excluding hair loss and neurotoxicity, which have been determined by the researchers to be irreparable and level 2 hypothyroidism for a long time). Previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous of LM103<br>≥5×10^9 cells (LM103) will be infused i.v. to patients after NMA lymphodepletion treatment with Cyclophosphamide for Injection and Fludarabine Phosphate for Injection. | Biological: LM103<br>* Fresh tumor samples will be resected from enrolled patients. Autologous TILs will be extracted and reinfused to corresponding patients after ex vivo stimulation, activation and extensive expansion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AE), Serious adverse event (SAE) and immune related adverse events (irAE) | Incidence and severity of AE, SAE and irAE; Abnormal changes in laboratory and other tests with clinical significance. | through study completion, an average of 1 year estimate | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by investigator assessment based on RECIST version 1.1. | through study completion, an average of 1 year estimate | 
| Duration of response (DOR) | Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. | through study completion, an average of 1 year estimate | 
| Disease control rate (DCR) | Disease control rate (DCR) was defined as the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST version 1.1. | through study completion, an average of 1 year estimate | 
| Time to response (TTR) | Time to response (TTR) is defined as the time from randomization until the first documented evidence of CR or PR. | through study completion, an average of 1 year estimate | 
| Time to disease progression (TTP) | Time to progression (TTP) is defined as the interval between the date of randomization and the earliest date of progression of disease (PD) or death due to the solid tomor. | through study completion, an average of 1 year estimate | 
| Progression free survival (PFS) | Progression-free survival (PFS) was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST version 1.1) or death due to any cause. | through study completion, an average of 1 year estimate | 
| Overall survival (OS) | OS was defined as the time from first dose to date of death from any cause. | through study completion, an average of 1 year estimate | 
| Peripheral blood TILs cell survival | Detection using flow cytometry | through study completion, an average of 1 year estimate | 
| Lymphocyte subpopulations | CD3+, CD4+, CD8+, CD4+/CD8+.Detection using flow cytometry | through study completion, an average of 1 year estimate | 
| Cytokines | IFN- γ、 TGF- β. Detection using flow cytometry | through study completion, an average of 1 year estimate | 
| Diversity of Immune repertoire | Sequence and abundance of T Cell Receptor,B Cell Receptor | through study completion, an average of 1 year estimate | 
| Changes in T cell transcriptome | Track the changes in the clonal frequency of infused TILs, study the transcriptomic dynamics of memory-, activation-, effector function-, exhaustion-, and metabolic fitness-assocated genes in the infused TILs, GSEA and pathway analysis. | through study completion, an average of 1 year estimate | 
| Level of tumor markers | The expression levels of CA50, CA199 and CEA in Melanoma, CA125, SCC and CA199 in cervical cancer/ovarian cancer, CYFRA21-1, SCC and CEA in non-small cell lung cancer, and CEA, TG and SCC in Head and neck cancer | through study completion, an average of 1 year estimate |