A Multicenter, Randomized, Controlled,Open Label, Phase II Trial of Autologous Tumor Infiltrating Lymphocytes (GC101 TIL) in Subjects With Advanced Melanoma

Phase 2

Recruiting

• Conditions: Melanoma
• Interventions: Biological: GC101 TIL; Drug: dacarbazine, temozolomide, paclitaxel ,platinum or cisplatin

• Registration Number: NCT06703398
• Lead Sponsor: Shanghai Juncell Therapeutics

Brief Summary

98 participants will be randomly assigned 1:1 to the experimental group and the control group for the Phase II clinical trial，this trail is expected to be finished in 24 months

Detailed Description

This study is to investigate the efficacy and safety of autologous tumor infiltrating lymphocyte (GC101 TIL) therapy versus investigator's choice of chemotherapy in patients with advanced melanoma. Autologous TILs are expanded from tumor resections or biopsies and infused i.v. into the patient after NMA lymphodepletion treatment with cyclophosphamide and hydroxychloroquine.

Study Timeline

• Study First Submitted: 2024-11-21
• Study First Submitted QC: 2024-11-22
• Study First Posted: 2024-11-25
• Study Start: 2024-12-20
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-23
• Last Update Posted: 2025-01-27
• Primary Completion: 2026-07-10
• Study Completion: 2026-12-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

• Signed the informed consent form (ICF) and able to comply with the visits and related procedures specified in the protocol;
• Aged ≥18 years and ≤75 years, regardless of gender;
• Patients with unresectable advanced, recurrent or metastatic melanoma (excluding uveal melanoma) ;
• Patients who have failed or resisted to PD-1 antibodies；
• TILs can be isolated from a surgically resectable tumor region: the tissue volume must be >150mm3, and the lesion has not received local treatment (such as radiotherapy, radiofrequency ablation, oncolytic virus, etc.) or progressed after local treatment;There are still at least 1 measurable lesion (according to RECIST1.1 criteria [see Appendix 4]) even after TIL sampling and resection of surgically resectable tissue;
• ECOG performance status 0-1;
• Expected survival time >3 months;
• With sufficient hematology and end-organ function;
• Good compliance and able to adhere to the study visit plan and other agreement requirements.

Exclusion Criteria

• Participation in a clinical trial of another drug or biologic therapy or receipt of a comparable cellular therapy within 28 days prior to screening;
• Combination of 2 or more malignant tumors, except: Eradicated malignant tumors that have been inactive for ≥5 years prior to study entry and are at minimal risk of recurrence; adequately treated non-melanoma skin cancer or malignant nevus of freckle-like nevus without evidence of disease recurrence; adequately treated carcinoma in situ without evidence of disease recurrence;
• Has received live attenuated vaccination after signing informed consent or is scheduled to receive it during the study;
• Has not recovered from a prior procedure or treatment-related adverse reaction to ≤ grade 1 nci ctcae 5.0 (except for toxicities such as alopecia, etc., which in the judgment of the investigator pose no safety risk);
• Known history of allergy to streptomycin, ciprofloxacin, or micafungin or allergy to any component of the infused product formulation;
• Uncontrolled co-morbidities including, but not limited to, uncontrolled arterial hypertension (systolic blood pressure ≥160 mmhg and/or diastolic blood pressure ≥100 mmhg) even with standardized treatment or any unstable cardiovascular disease including transient ischemic attack, cerebrovascular accident, myocardial infarction, unstable angina pectoris within 6 months prior to enrollment; new york heart association ( nyha class iii or iv congestive heart failure with an ejection fraction <50%; or severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias, degree ii-iii atrioventricular block, etc., requiring clinical intervention; ecg results showing clinically significant abnormalities or a qtcf ≥450ms (if the first test is abnormal, it may be retested at least 5 minutes apart twice and the combined result/mean value to determine eligibility) ;
• Patients with esophageal or gastric varices that require immediate intervention (e.g., taping or sclerotherapy) or are considered to be at high risk for bleeding based on the opinion of the investigator or consultation with a gastroenterologist or hepatologist, have evidence of portal hypertension (including splenomegaly detected on imaging), or have a prior history of variceal bleeding must have undergone endoscopic evaluation within 3 months prior to enrollment;
• Uncontrolled metabolic disorders, such as diabetes mellitus known to be uncontrolled, or other non-malignant organ or systemic diseases or secondary reactions to cancer, and which can lead to higher medical risk and/or uncertainty in survival evaluation;
• Hepatic encephalopathy, hepatorenal syndrome or child-pugh class b or more severe cirrhosis, liver failure;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GC101 TIL group	GC101 TIL	A tumor sample is resected from each participant and cultured ex vivo to expand the population of autologous tumor infiltrating lymphocytes injection (GC101 TIL). After lymphodepletion, patients are infused GC101 TIL followed sintilimab.
Investigator's choice of chemotherapy	dacarbazine, temozolomide, paclitaxel ,platinum or cisplatin	monotherapy or combination of dacarbazine, temozolomide, paclitaxel,carboplatin or cisplatin, and the chemotherapy's dosage could refer to the drug label or the relevant treatment guideline, the final decision is up to investigator.

Primary Outcome Measures

Name	Time	Method
Progression-free survival	Every 6 weeks for 12 months	Progression-free survival (PFS) confirmed by the Independent Review Committee (IRC) according to RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
Overall survival	Maximum 2 years	Overall survival (OS) and OS rates at 6, 12, and 18 months
Progression-free survival	Every 6 weeks for 12 months	PFS assessed by investigators according to RECIST 1.1 and PFS assessed by IRC and investigators according to iRECIST
Objective Response Rate	Maximum 360 days	Objective Response Rate (ORR) assessed by IRC and investigators according to RECIST 1.1 and iRECIST
Disease Control Rates	Every 6 weeks for 12 months	Disease Control Rates (DCR) assessed by IRC and investigators according to RECIST 1.1 and iRECIST
Duration of Response	Every 6 weeks for 12 months	Duration of Response (DoR) assessed by IRC and investigators according to RECIST 1.1 and iRECIST
Adverse Events	Maximum 360 days	Incidence of adverse events associated with GC101 TIL retransfusion

Trial Locations

Locations (1)

Beijing Cancer Hospital; 🇨🇳 Beijing, China