Melanoma
Conditions
Interventions
Control group:Comparator drugs include dacarbazine, temozolomide, paclitaxel, and carboplatin/cisplatin. They can be used as monotherapy or in combination chemother
Experimental group:LM103 Injection
Sponsors
Beijing Cancer Hospital (Peking University Cancer Hospital)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Must be aged >=18 and = 3 months; 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 4. Patients with unresectable recurrent/metastatic melanoma (except uveal melanoma) who failed to respond to at least two lines of standard therapy: (1) failed to respond to or were intolerant to PD-1 antibody therapy. Details of treatment failures are provided in Appendix 4. Intolerance was defined as the occurrence of immune-related adverse events (irAE) of grade >=3 after PD-1 antibody treatment leading to the discontinuation of PD-1 antibody. (2) If BRAF V600 mutation is positive, BRAF±MEK inhibitor therapy should be failed; (3) If NRAS mutation is positive, treatment failure with tollatinib is required. 5. Have a needle that can be used for surgical resection (> 1.0cm3) or biopsy (needle specimen: 16G>=4, 18G>=6, and the specific type of puncture needle and the number of puncture specimens could also be communicated with the sponsor according to the puncture site and the size of the puncture specimen) and measurable residual lesions after resection for TILs collection and efficacy evaluation. The sampled lesions had not received local treatment (such as radiotherapy, radiofrequency therapy, oncolytic virus, etc.). 6. At least one measurable lesion (according to RECIST1.1 criteria) even after resection/biopsy; 7. Good organ function according to screening laboratory results: (1) Hematology (no blood transfusion and no treatment with blood components or granulocyte colony-stimulating cytokines within 14 days) : absolute neutrophil count (ANC) >=1.0×10^9/L; Platelet count (PLT) >=80×10^9/L; Hemoglobin (HGB) >=90 g/L; Absolute lymphocyte count >=0.8×10^9/L, or lymphocyte percentage >=20%; White blood cell count >=3.0×10^9/L. (2) Liver: 1)Serum total bilirubin (TBil) =60 mL/min (calculated by Cockcroft-Gault formula);2)Urine protein 1.0g/L, 24-hour urine protein should be collected for determination, and the total amount of urine protein should be =1g to allow enrollment). (4) Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (APTT) 60% or FEV1/FVC > 0.7; (7) Blood oxygen saturation >=93% in non-oxygen inhalation state; (8) Left ventricular ejection fraction (LVEF) >=50% was detected by echocardiography. 8. Male participants with reproductive capability or female participants who could become
Exclusion criteria
Exclusion criteria: 1. A history of malignant tumors other than the study disease within the past 5 years, except for malignant tumors that are expected to be cured after treatment (including but not limited to adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated with radical surgery); 2. Adverse reactions caused by previous treatments have not recovered to CTCAE (v5.0) grade 1 or below (excluding hair loss and neurotoxicity, as well as hypothyroidism, adrenal insufficiency, and pituitary insufficiency that are determined by the investigator to be long-standing and unable to recover to grade 2). 3. Any CTCAE (v5.0) immune-related adverse events (irAEs) that led to permanent discontinuation during previous immunotherapy, with a severity grade greater than 3; 4. Those who have received a vaccination within 2 months before signing the informed consent form, or plan to receive a vaccination during the study; 5. Within 3 weeks prior to tumor tissue collection, the patient received systemic cytotoxic drug treatment, radiotherapy, targeted therapy (the withdrawal period for small molecule targeted drugs can be shortened to 5 half-lives of the drug used), anti-angiogenic drugs, or herbal/Chinese patent medicines with anti-tumor indications and unknown mechanisms. Within 7 days prior to tumor tissue collection, the patient received systemic corticosteroids (>5 mg/day prednisone or an equivalent dose of other glucocorticoids) or other immunosuppressive drugs; 6. Participation in other drug or biological therapy clinical trials within 4 weeks before the current time or before signing the informed consent; receiving TIL cell therapy, allogeneic T-cell therapy, or NK cell therapy within 6 months before signing the informed consent; 7. If the researcher determines that it is necessary to use glucocorticoids (i.e., >5 mg/day of prednisone or an equivalent dose of other glucocorticoids) or other immunosuppressive drugs during the study period, excluding topically absorbed glucocorticoids; 8. Previously received an allogeneic hematopoietic stem cell transplant or solid organ transplant; 9. Patients with central nervous system metastases and/or carcinomatous meningitis. Subjects who have previously received treatment for brain metastases may be considered for participation in this study, provided that their condition has been stable for at least 6 months, and imaging conducted within 4 weeks prior to LM103 infusion confirms that there has been no disease progression, with no evidence of new or enlarged brain metastases. 10. Having or suspected of having active autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, etc.; 11. Patients with clinical symptoms or a large amount of pleural or abdominal effusion requiring symptomatic treatment; 12. Patients with current or past irreversible interstitial lung disease (excluding those caused by radiotherapy); 13. Patients with severe cardiovascular or cerebrovascular diseases, such as: hypertension that is poorly controlled despite standard treatment (systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg) or pulmonary hypertension; unstable angina or myocardial infarction, coronary artery bypass grafting, or stent implantation within 6 months prior to study medication; chronic heart failure with New York Heart Association (NYHA) class >= II; se
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| IRC-assessed PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Related to adverse events;Investigator-assessed PFS according to RECIST 1.1;Overall survival;Objective response rate as assessed by the IRC and investigators according to RECIST 1.1;Disease control rates as assessed by the IRC and investigators according to RECIST 1.1;Duration of response as assessed by the IRC and investigators according to RECIST 1.1; | — |
Countries
China
Contacts
Public ContactJun Guo
Beijing Cancer Hospital (Peking University Cancer Hospital)
Outcome results
None listed