Solid Tumor
Conditions
Brief summary
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.
Interventions
BIOLOGICALLM103
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.
Sponsors
Suzhou BlueHorse Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. The expected survival time is not less than 3 months. 2. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-1. 3. 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. 4. 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. 5. At least one measurable lesion as the target lesion after collecting tumor tissue from the patient (RECIST v1.1 criteria). 6. Laboratory tests results during the screening period indicate that the subjects have sufficient organ function.
Exclusion criteria
1. 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). 2. 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. 3. 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). 4. Previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events (AE), Serious adverse event (SAE) and immune related adverse events (irAE) | through study completion, an average of 1 year estimate | Incidence and severity of AE, SAE and irAE; Abnormal changes in laboratory and other tests with clinical significance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DOR) | through study completion, an average of 1 year estimate | 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. |
| Disease control rate (DCR) | through study completion, an average of 1 year estimate | 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. |
| Time to response (TTR) | through study completion, an average of 1 year estimate | Time to response (TTR) is defined as the time from randomization until the first documented evidence of CR or PR. |
| Time to disease progression (TTP) | through study completion, an average of 1 year estimate | 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. |
| Progression free survival (PFS) | through study completion, an average of 1 year estimate | 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. |
| Overall survival (OS) | through study completion, an average of 1 year estimate | OS was defined as the time from first dose to date of death from any cause. |
| Objective response rate (ORR) | through study completion, an average of 1 year estimate | 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. |
| Lymphocyte subpopulations | through study completion, an average of 1 year estimate | CD3+, CD4+, CD8+, CD4+/CD8+.Detection using flow cytometry |
| Cytokines | through study completion, an average of 1 year estimate | IFN- γ、 TGF- β. Detection using flow cytometry |
| Diversity of Immune repertoire | through study completion, an average of 1 year estimate | Sequence and abundance of T Cell Receptor,B Cell Receptor |
| Changes in T cell transcriptome | through study completion, an average of 1 year estimate | 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. |
| Level of tumor markers | through study completion, an average of 1 year estimate | 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 |
| Peripheral blood TILs cell survival | through study completion, an average of 1 year estimate | Detection using flow cytometry |
Countries
China
Contacts
Primary ContactFeng'e LI
Outcome results
None listed