A Study on the Efficacy of Androgen Deprivation Therapy Combined With Anti-PD-1 Therapy in Advanced Lung Cancer

Jinzhou Medical University

Status: Enrolling

Conditions: NSCLC, Stage IV; NSCLC, Stage III

Treatments: Drug: Sintilimab; Drug: Leuprorelin acetate + Sintilimab

Study type: Interventional

Funder types: Other

Identifiers

NCT06512207

NSFC-32230037

Details and patient eligibility

About

Androgen Deprivation Therapy (ADT) triggers thymic revitalization and increases thymic output, enhancing baseline anti-tumor immunity and responses to immunotherapies. Anti-tumor synergism has been identified by combining ADT with anti-PD-1 immunotherapy for androgen-independent tumors. This study is to investigate the combination of Leuprorelin ADT and Sintilimab (anti-PD-1) therapy in patients with advanced lung cancer.

Full description

Immune checkpoint blockades (ICBs) are widely used in the clinical treatment of lung cancer. Studies have shown that the quantity and function of tumor-infiltrating lymphocytes (TILs) are associated with the effectiveness of PD-1 inhibitors in treating advanced NSCLC. The thymus is crucial for the differentiation, development, and maturation of T cells. With age, thymic atrophy leads to immunosenescence, significantly affecting baseline anti-tumor immunity and responses to immunotherapies. Preliminary findings have indicated that androgen deprivation therapy (ADT) not only directly induces apoptosis in prostate cancer cells but also may exert anti-tumor effects by promoting thymic regeneration. Furthermore, anti-tumor synergism has been identified by combining ADT with anti-PD-1 immunotherapy for androgen-independent tumors. Therefore, this study aims to investigate the combination of Leuprorelin ADT and Sintilimab (anti-PD-1) therapy in patients with advanced lung cancer.

Enrollment: 80 estimated patients

Sex: Male

Ages: 60+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

3.Inclusion Criteria:

1. Male patients aged ≥60 years.

2. ECOG performance status score of 0 ~1.

3. Expected survival time of more than 3 months.

4. Histologically or cytologically diagnosed advanced lung cancer according to the TNM staging system established by AJCC.

5. Patients who have not previously received any anti-PD-1 treatment.

6. Patients with adequate bone marrow function, no significant hepatic, renal, or coagulation dysfunction as per laboratory test criteria.

7. At least one tumor lesion meeting the following criteria:

   • No prior local treatments such as radiotherapy
   • Not biopsied during the screening period (if biopsy needed, baseline tumor assessment at least 14 days after the screening biopsy).
   • Measurable at baseline (longest diameter of the lesion ≥10 mm; For a lymph node, short diameter ≥15 mm).
   • If only one measurable lesion, no prior local treatments such as radiotherapy.

8. Ability to understand and voluntarily sign a written informed consent form.

9. Willingness to follow the study protocol and follow-up examinations.

Exclusion Criteria:

• Exclusion of cases that do not meet the inclusion criteria

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

Conventional Treatment Group

Active Comparator group

Description:

40 cases in this group to receive the standard conventional treatment (Chemotherapy + PD-1 Monoclonal Antibody)

Treatment:

Drug: Sintilimab

Conventional Treatment Combined with Leuprolide Group

Experimental group

Description:

40 cases in this group to receive the standard conventional therapy (Chemotherapy + PD-1 Monoclonal Antibody) combined with Leuprorelin acetate, 3.75 mg

Treatment:

Drug: Leuprorelin acetate + Sintilimab