A Study of GC101 TIL in Advanced Melanoma (MIZAR-003)

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

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

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Biological: GC101 TIL; Drug: dacarbazine, temozolomide, paclitaxel ,platinum or cisplatin

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 Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jun Guo, Prof. Dr. Med; Phone Number: 86-10-88121122; Email: guoj307@126.com
• Study Contact Backup: Name: Wei Shi; Phone Number: 86-21-69110327; Email: wei.shi1@juncell.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Cancer Hospital
    • Contact: Jun Guo; Phone Number: +861088121122; Email: guoj307@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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；
• Patients must have failed or resisted to at least two frontlines systemic tehrapy(if knowed with BRAF V600 mutate, then need to failed to BRAF/MEK inhibitor; if knowed with NRAS mutate, then need to failed to Tunlametinib) ；
• 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 ) 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:

• Patients receive any drug under study 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, hypothyroidism 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;
• With other serious organic diseases or mental disorders;
• Suffering from systemic active infection requiring treatment, with positive blood culture or imaging evidence of infection, including but not limited to active tuberculosis;
• Suffering from infectious diseases such as hepatitis B, hepatitis C, syphilis, AIDS, etc;
• Individuals with active autoimmune diseases (such as eczema, vitiligo, psoriasis, alopecia or Graves' disease that do not require systemic treatment within the past two years, other autoimmune diseases that are not expected to recur, hypothyroidism that only requires thyroid hormone replacement therapy, and type 1 diabetes that only requires insulin replacement therapy can be enrolled);
• Any NCI CTCAE 5.0 immune-related adverse reaction (iRAE) grade ≥3 occurred during any previous immunotherapy(except for cases where it recovered to ≤1 after treatment or reached stability as assessed by the investigator);
• Those who had undergone organ allotransplantation, allogeneic stem cell transplantation and renal replacement therapy;
• Pulmonary fibrosis, interstitial lung disease (including past history and current condition), acute lung disease;
• Those with leptomeningeal metastasis;
• Patients with clinical symptoms of central nervous system metastases (such as cerebral edema, requiring hormone intervention, or progression of brain metastases), Patients who have previously received treatment for brain metastases, such as those who have maintained clinical stability (MRI) for at least 2 months and have stopped systemic hormone therapy (dose > 10mg/ day prednisone or other equivalent hormones) for more than 4 weeks, can be included;
• Women who are pregnant or breastfeeding;
• There is a history of TIL cell therapy, allogeneic T cell therapy, or NK cell therapy within 6 months;
• Situations that are not suitable for enrollment assesed by investigators;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GC101 TIL group; 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.	Biological: GC101 TIL; Patients with advanced melanoma (excluding uveal melanoma) who have failed to PD-1 antibodies (if BRAF mutation is present, BRAF and MEK inhibitors have failed; if NRAS mutation is present, tunlametinib have failed) and are ineligible for resection
Active Comparator: Investigator's choice of chemotherapy; 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.	Drug: dacarbazine, temozolomide, paclitaxel ,platinum or cisplatin; monotherapy or combination of dacarbazine, temozolomide, paclitaxel, platinum or cisplatun, and the chemotherapy's dosage could refer to the drug label or the relevant treatment guideline, the final decision is up to investigator

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shanghai Juncell Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Estimated): July 10, 2026
• Study Completion (Estimated): December 20, 2026

Study Registration Dates

• First Submitted: November 21, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Actual): November 25, 2024

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Chemotherapy; Tumor Infiltrating Lymphocytes; Randomized-controlled trial
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Triazenes; Imidazoles; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Temozolomide; Dacarbazine; Cisplatin
• Other Study ID Numbers: GC101 TIL-MM-II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No