Thymosin Alpha 1 Combined With Anti-PD-1 Monoclonal Antibody in Elderly Patients With Advanced Melanoma

Primary Objective:

To evaluate the effectiveness of Thymosin Alpha-1 combined with PD-1 monoclonal antibody in elderly patients with advanced melanoma .

Secondary Objective:

To evaluate the safety and tolerability of adenpeptide-α1 combined with PD-1 antibody in elderly patients with advanced melanoma .

Study Design：Open-label, single-arm, non-controlled clinical trial.

Primary Inclusion Criteria:

1. Age ≥60 years old;
2. Pathologically confirmed as inoperable or metastatic melanoma;
3. one or more lesions evaluable by RECIST1.1 standards.
4. The Eastern Cooperative Oncology Group (ECOG) scoring system in the United States scores from 0-2;

Main exclusion criteria:

1. Received treatment with a regimen containing PD-1, PD-L1, or CTLA-4 antibodies within the past 6 months;
2. Received thymosin class drug treatment within 3 months before signing the informed consent.
3. Symptomatic, untreated central nervous system metastases. Treatment： Thymosin Alpha 1 1.6mg, sc，QD，d1-7;1.6mg, sc， three times per week, d8-21. Each 21 days is considered one cycle, for a total of 12 weeks.

Anti-PD-1 monoclonal antibody (Toripalimab) 240mg per dose,ivdrip，Q3W，4 cycles.

Primary study endpoints:

Objective Response Rate (ORR: CR+PR)

Secondary study endpoints:

Progression-Free Survival (PFS), Duration of Response (DOR), Overall Survival (OS) Adverse Events (AEs)

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Immune Checkpoint Inhibitor; Immune-related Adverse Event
• Intervention / Treatment: Drug: Thymosin Alpha 1 and Anti-PD-1 monoclonal antibody

• Study Type: Interventional
• Enrollment (Estimated): 55
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xizhi Wen, phD; Phone Number: +8602087343381; Email: wenxzh@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun yat-sen uniersity
      • Contact: Xizhi Wen, phD; Phone Number: +8602087343381; Email: wenxzh@sysucc.org.cn
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Nanshan hospital
      • Contact: qiming zhou, phD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Aged 60 years or older;
2. Diagnosis of malignant melanoma confirmed by pathological histology or cytology examination.
3. According to the 8th edition of AJCC staging, patients with unresectable stage III or IV melanoma;
4. One or more lesions evaluable by RECIST1.1 standards.
5. The Eastern Cooperative Oncology Group (ECOG) scoring system in the United States has a score range of 0-2.
6. Total bilirubin ≤1.5× upper limit of normal (ULN); AST and AST <2.5× upper limit of normal (ULN).(No liver metastasis), or <5 times the upper limit of normal (ULN) (with liver metastasis);

7. Patients with recurrent metastasis who have not previously received immunotherapy such as PD-1, PD-L1, CTLA-4 antibodies，also allowed for the enrollment of patients who had used adjuvant/neoadjuvant therapies

   • If the adjuvant or neoadjuvant treatment plan includes PD(L)-1 or CTLA-4 monoclonal antibodies, it is required that only those who progress more than 6 months after the end of the treatment plan can be included in the study group.
   • If the adjuvant or neo-adjuvant treatment plan does not include PD(L)-1 or CTLA-4 monoclonal antibodies, patients who progress during the adjuvant treatment are allowed to participate in the study.
8. Has signed the informed consent form, able to comply with the study protocol and follow-up plan.

Exclusion Criteria:

1. Received treatment involving PD-1, PD-L1, or CTLA-4 antibody regimen within the past 6 months;
2. Patients who have received treatment with thymosin, thymopentin, or thymosin a-1d within 3 months prior to enrollment.
3. Presence of symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. For subjects with previously treated CNS metastases, if the subject's condition is stable (no evidence of radiographic progression for at least weeks prior to the first administration of the study intervention, and all neurological symptoms have returned to baseline), repeat radiographic examination confirms no evidence of new brain metastases or enlargement of existing brain metastases, and no need for steroid treatment for at least 14 days prior to the first administration of the study intervention, they may participate in the study.
4. Patients with active systemic autoimmune diseases requiring systemic treatment (i.e., using immunomodulators, corticosteroids, or immunosuppressants). Replacement therapies (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are not considered systemic treatment.
5. Has a history of immunodeficiency, including testing positive for HIV, or suffering from other acquired or congenital immunodeficiency diseases, or has a history of organ transplantation and bone marrow transplantation.

6）Allergic to the investigational drug or its components; 7）Presence of active infection requiring systemic treatment; 8) Uncontrolled internal medical complications, such as unstable congestive heart failure, unstable angina, myocardial infarction, cerebrovascular accidents, and hemodynamically unstable arrhythmias, etc.

9) The investigator deems them unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intervention group; Thymosin Alpha 1 and anti-PD-1 monoclonal antibody	Drug: Thymosin Alpha 1 and Anti-PD-1 monoclonal antibody; Thymosin Alpha 1 1.6mg, sc，QD，d1-7;1.6mg, sc，three times per week, d8-21 Anti-PD-1 monoclonal antibody (Toripalimab) 240mg per dose,ivdrip，Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	defined as the best overall response of complete remission or partial remission,	up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)		Assessed until 12 months after the first dose of the last enrolled patient, estimated up to 5 years.
overall survival (OS)	defined as the time from enrollment to death due to any cause.	Assessed until 12 months after the first dose of the last enrolled patient, estimated up to 5 years.
Adverse Events (AEs)	Signs, symptoms or abnormal laboratory test related to treatment	Assessed until 12 months after the first dose of the last enrolled patient, estimated up to 5 years.
Duration of Response (DOR),		Assessed until 12 months after the first dose of the last enrolled patient, estimated up to 5 years.

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Director: Xiaoshi Zhang, phD; Principal Investigator: Penghui Zhou, PhD; Principal Investigator: Ya Ding, PhD; Principal Investigator: Dandan Li, PhD; Principal Investigator: Jingjing Zhao, PhD

Publications and helpful links

General Publications

• Garaci E, Pica F, Serafino A, Balestrieri E, Matteucci C, Moroni G, Sorrentino R, Zonfrillo M, Pierimarchi P, Sinibaldi-Vallebona P. Thymosin alpha1 and cancer: action on immune effector and tumor target cells. Ann N Y Acad Sci. 2012 Oct;1269:26-33. doi: 10.1111/j.1749-6632.2012.06697.x.
• Romani L, Bistoni F, Perruccio K, Montagnoli C, Gaziano R, Bozza S, Bonifazi P, Bistoni G, Rasi G, Velardi A, Fallarino F, Garaci E, Puccetti P. Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance. Blood. 2006 Oct 1;108(7):2265-74. doi: 10.1182/blood-2006-02-004762. Epub 2006 Jun 1.
• Maio M, Mackiewicz A, Testori A, Trefzer U, Ferraresi V, Jassem J, Garbe C, Lesimple T, Guillot B, Gascon P, Gilde K, Camerini R, Cognetti F; Thymosin Melanoma Investigation Group. Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. J Clin Oncol. 2010 Apr 1;28(10):1780-7. doi: 10.1200/JCO.2009.25.5208. Epub 2010 Mar 1.
• Giuliani C, Napolitano G, Mastino A, Di Vincenzo S, D'Agostini C, Grelli S, Bucci I, Singer DS, Kohn LD, Monaco F, Garaci E, Favalli C. Thymosin-alpha1 regulates MHC class I expression in FRTL-5 cells at transcriptional level. Eur J Immunol. 2000 Mar;30(3):778-86. doi: 10.1002/1521-4141(200003)30:33.0.CO;2-I.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2023
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• 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; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Thymosin; Thymus Hormones; Thymalfasin
• Other Study ID Numbers: xizhiwen

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