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

Jinzhou Medical University80 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

NSCLC, Stage III

Eligibility

Sex: MALEMin age: 60 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Number of Participants with Complete Response (CR)

Disappearance of all target lesions, with nodular diseases excluded and target nodules reduced to \<10mm in short axis.

Time frame: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment

Number of Participants with Partial Response (PR)

Reduction of at least 30% in the sum of diameters of all measurable target lesions compared to baseline

Time frame: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment

Number of Participants with Disease Progression (PD)

A 20% increase in the sum of the diameters of all measurable target lesions over the entire study period (using the smallest baseline value if it is the smallest), coupled with an absolute increase in the sum of diameters of at least 5mm. The appearance of one or more new lesions is also considered disease progression.

Time frame: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment

Number of Participants with Stable Disease (SD)

Lesion reduction not meeting PR criteria nor sufficient increase for PD, falling in between these two endpoints. The minimum sum of diameters during the study period can be used as a reference.

Time frame: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment

Quantity of Peripheral Blood Lymphocytes

Assessment of peripheral blood lymphocyte quantity, comparing patients before and after a treatment cycle

Time frame: Laboratory evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment

Composition of Peripheral Blood Lymphocytes

Assessment of peripheral blood lymphocyte composition, comparing patients before and after a treatment cycle

Time frame: Laboratory evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment.

Status of Recent Thymic Emigrants (RTEs)

Assessment of the status of Recent Thymic Emigrants (RTEs), comparing patients before and after a treatment cycle

Time frame: Evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment.

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Central Contacts