LM103 treatment for advanced melanoma (Phase II)

A Multicenter, Randomized, Controlled, Open-label, Phase II Trial on Autologous Tumor Infiltrating Lymphocyte Injection (LM103 TILs) for the Treatment of Advanced Melanoma

This study will test whether LM103 tumor‑infiltrating lymphocytes (TIL) given with chemotherapy can help adults with advanced melanoma who have not responded to at least two prior treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 92 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Suzhou BlueHorse Therapeutics Co., Ltd. (Industry-sponsored)
• Drugs / interventions: Tunlametinib, immunotherapy
• Locations: 13 sites (Beijing, Beijing Municipality and 12 other locations)
• Trial ID: NCT07310784 on ClinicalTrials.gov

What this trial studies

In this randomized Phase II trial, 92 adults with unresectable or metastatic melanoma who have failed at least two prior systemic therapies will be assigned 1:1 to receive LM103 TIL injections or a control regimen. The control arm involves standard chemotherapies such as dacarbazine, temozolomide, paclitaxel, or platinum agents per protocol. Participants must have tumor tissue available for TIL generation and at least one measurable lesion by RECIST 1.1 after biopsy or resection. Safety and tumor response will be followed for up to 24 months after treatment.

Who should consider this trial

Good fit: Adults 18–75 with unresectable recurrent or metastatic melanoma (excluding uveal melanoma), ECOG 0–1, expected survival >3 months, adequate organ function, and who have failed at least two prior lines of therapy including PD‑1 antibodies are ideal candidates.

Not a fit: Patients with recent other malignancies, poor organ function, ECOG >1, or who cannot provide tumor tissue for TIL production are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, LM103 could produce tumor shrinkage and longer disease control for patients who have exhausted standard therapies.

How similar studies have performed: Other TIL therapies have produced durable responses in some heavily pretreated melanoma patients, so the approach has precedent although LM103 itself remains investigational.

Eligibility criteria

Inclusion Criteria:

* At the date of signing Informed Consent Form (ICF), 18 \~75 years old, male or female;
* Expected survival time \>3 months;
* ECOG performance status 0-1;
* Patients with unresectable recurrent/metastatic melanoma (excluding uveal melanoma) who have failed at least two lines of standard treatment: • Patients need to have failed or be intolerant to PD-1 antibody treatment; • If the BRAF V600 mutation is positive, treatment with BRAF±MEK inhibitors must fail; • If the NRAS mutation is positive, treatment with Tunlametinib must fail;
* Patients have lesions that can be used for surgical resection or biopsy puncture;
* Even after tumor tissue resection/biopsy puncture, there should still be at least one measurable lesion (according to RECIST1.1);
* Patients have sufficient hematology and organ functions;
* Voluntarily sign a written informed consent form (ICF).

Exclusion Criteria:

* A history of other malignant tumors within the past 5 years, excluding malignant tumors that can be expected to heal after treatment (including but not limited to well-treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated by radical surgery);
* Adverse reactions caused by previous treatments have not been recovered to grade ≤1(CTCAE V5.0) (excluding the laboratory tests from the inclusion criteria, alopecia and neurotoxicity, and hypothyroidism, adrenal insufficiency and hypopituitarism that cannot be restored to grade 2 as determined by the investigators for a long time);
* Any immune-related adverse reaction (irAE) with a severity level greater than grade 3 that has occurred during any previous immunotherapy and has been permanently discontinued;
* Have received vaccination within two months prior to tumor tissue procurement surgery, or plan to receive vaccination during the study;
* Have received TIL cell therapy, allogeneic T cell therapy or NK cell therapy within 6 months prior to signing the ICF;
* Have received allogeneic hematopoietic stem cell transplantation or solid organ transplantation in the past;
* Suffering from central nervous system metastases and/or cancerous meningitis. Patients who have received brain metastasis treatment and whose conditions have been stable for at least 6 months, and there is no evidence of new or expanded brain metastases may consider participating in this study;
* Suffering from or suspected of having an active autoimmune disease;
* Suffering from a large amount of pleural effusion or ascites with clinical symptoms or requiring symptomatic treatment;
* Patients with current or previous irreversible interstitial lung disease;
* Suffering from serious cardiovascular and cerebrovascular diseases;
* Suffering from an active infection that requires systemic treatment;
* Suffering from infectious diseases such as hepatitis B, hepatitis C, syphilis, AIDS;
* Patients with esophageal or gastric varices requiring immediate intervention (such as ligation or sclerotherapy), or those with a higher risk of bleeding as recommended by the investigator or gastroenterologist or hepatologist, evidence of portal hypertension (including splenomegaly found in imaging examinations), or a history of variceal bleeding must undergo endoscopic assessment within 3 months before enrollment;
* Uncontrolled metabolic disorders, such as diabetes, or other non-malignant organ or systemic diseases or secondary reactions to cancer, can lead to higher medical risks and/or uncertainties in survival assessment;
* Those who are known to be allergic to any component of the investigational drug and the LM103 product formula;
* Women who are pregnant or breastfeeding;
* As determined by the investigators, there are other severe, acute or chronic medical diseases, mental disorders or laboratory abnormalities that may increase the risks related to participation in the study or may interfere with the interpretation of the study results.

Where this trial is running

Beijing, Beijing Municipality and 12 other locations

• Beijing Go Broad Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (Recruiting)
• Sun Yat-Sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• Guangxi Medical University Cancer Hospital — Nanning, Guangxi, China (Recruiting)
• The First Affiliated Hospital of Guangxi Medical University — Nanning, Guangxi, China (Recruiting)
• The Third People's Hospital of Zhengzhou — Zhengzhou, Henan, China (Recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Nanjing Drum Tower Hospital — Nanjing, Jiangsu, China (Recruiting)
• The Second Affiliated Hospital of Xi'an Jiaotong University — Xi’an, Shanxi, China (Recruiting)
• West China Hospital of Sichuan University — Chengdu, Sichuan, China (Recruiting)
• Tianjin Medical University Cancer Institute & Hospital — Tianjin, Tianjin Municipality, China (Recruiting)
• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)
• Beijing Cancer Hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Jun Guo, Prof. Dr. Med

Conditions Advanced Melanoma