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

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)

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.