Neoadjuvant Adebrelimab Plus CRT for Locally Advanced Thymic Carcinoma

Official title

A Single-Arm, Prospective, Phase II Trial of Adebrelimab Plus Albumin-Bound Paclitaxel, Cisplatin, and Concurrent Radiotherapy for Neoadjuvant Treatment of Locally Advanced Thymic Carcinoma

Overview

The goal of this clinical trial (Phase II) is to evaluate the efficacy and safety of neoadjuvant Adebrelimab combined with chemoradiation in patients with locally advanced thymic carcinoma. The main questions it aims to answer are: * Is neoadjuvant therapy with Adebrelimab plus chemoradiation effective? * Is this combination treatment safe and tolerable in this patient population? Participants will: * Receive 2-4 cycles of neoadjuvant Adebrelimab combined with a platinum-based chemotherapy regimen (such as carboplatin plus paclitaxel) and concurrent radiotherapy prior to surgery. * Undergo re-staging imaging to assess tumor response and determine surgical candidacy. * Undergo surgical resection if the tumor is resectable after neoadjuvant treatment. * Receive adjuvant Adebrelimab therapy for up to one year following surgery. * Undergo regular follow-up visits for safety monitoring and survival assessment.

Interventions

• Other adebrelimab plus chemoradiation
  All patients will receive 2 cycles of adebrelimab (1200mg, D1, Q1W) in combination with albumin-bound paclitaxel (70mg/m2, D1/D8/D15/D22)plus cisplatin (25mg/m2, D1/D8/D15/D22), and concurrent radiotherapy (40Gy) before surgery. If tumors are resectable after neoadjuvant therapy, surgery will be scheduled. After surgery, patients will receive adjuvant chemotherapy (2 cycles), radiotherapy (20Gy) (except for PCR disease), and adebrelimab for up to 1 year. If tumors are still unresectable after ne

Primary outcome measures

• the objective response rate to neoadjuvant therapy [Time frame: From enrollment to 2-4 weeks after neoadjuvant therapy]
• the rate of major pathologic response to neoadjuvant therapy [Time frame: From enrollment to 1 month after surgery]

Secondary outcome measures (5)

• the rate of surgery [Time frame: From date of enrollment until the date of surgery, around 4-6 weeks after finishing neoadjuvant treatment]
• the rate of complete pathological response to neoadjuvant therapy [Time frame: From enrollment to 1 month after surgery]
• adverse event [Time frame: From date of enrollment until 3 months after the end of treatment]
• PFS [Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months]
• OS [Time frame: From date of enrollment until the date of death from any cause, whichever came first, assessed up to 36 months]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 and ≤ 75 years old at the time of signing the informed consent form, both male and female are eligible.
• Histologically confirmed thymic carcinoma.
• Potentially resectable locally advanced (T3/4NxM0). No previous treatment for thymic carcinoma, including but not limited to surgery, local radiotherapy, chemotherapy, immunotherapy, targeted drug therapy, and other investigational drug therapy.
• At least one measurable lesion according to RECIST 1.1 criteria.
• ECOG PS score: 0-1.
• Expected survival ≥ 3 months.
• Important organ functions must meet the following standards:

1\) Blood routine test: (No blood transfusion or use of G-CSF and other cytokine drugs for correction within 2 weeks before screening);

• Hemoglobin (HB) ≥ 90 g/L;
• Absolute neutrophil count (ANC) ≥ 1.5×109/L;
• Platelet count (PLT) ≥ 90×109/L;
• White blood cell count (WBC) ≥ 3.0×109/L and < 15×109/L; 2) Other tests: (No human albumin injection within 14 days before screening);

a) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3×ULN; b) Total bilirubin (TBIL) ≤ 1.5×ULN; c) Albumin (ALB) ≥ 30 g/L; d) Creatinine (Cr) ≤ 1.5×ULN, or creatinine clearance rate (CrCL) ≥ 50 mL/min (Cockcroft-Gault formula); e) Thyroid stimulating hormone (TSH) ≤ 1×ULN (If TSH is abnormal, FT3/T3 and FT4/T4 levels should also be examined. If FT3/T3 and FT4/T4 are normal, the patient can be enrolled); f) Activated partial thromboplastin time (APTT) ≤ 1.5×ULN, international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5×ULN (No anticoagulant therapy); g) Left ventricular ejection fraction (LVEF) ≥ 50%. 8. Non-surgically sterilized or female patients of childbearing age must have a negative serum pregnancy test within 3 days before the first dose of the study drug and must not be lactating. Female patients of childbearing age or male patients whose partners are of childbearing age must agree to use highly effective contraceptive methods during the study and for 6 months after the last administration of the study drug.

9\. Patients must voluntarily join this clinical study, sign the informed consent form, have good compliance, and be able to cooperate with follow-up.

Exclusion criteria

• Patients with pathologies of thymoma or thymic neuroendocrine tumor.
• Patients with other malignant tumors within the past 3 years or concurrently, except for those with cured skin basal cell carcinoma, superficial bladder cancer, skin squamous cell carcinoma, cervical carcinoma in situ, and ductal carcinoma in situ of the breast.
• Patients with interstitial pneumonia/interstitial lung disease (excluding those with only imaging changes), those requiring systemic glucocorticoid treatment for pneumonia (such as radiation-induced pneumonia, etc.), those with active pneumonia or severe lung function impairment confirmed by pulmonary function tests.
• Patients with any active or known autoimmune diseases (including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis, vasculitis, glomerulonephritis, uveitis, hypophysitis, hyperthyroidism, etc.). Patients with type 1 diabetes on stable insulin therapy, hypothyroidism requiring only hormone replacement therapy, and skin diseases (such as eczema, vitiligo or psoriasis) that do not require systemic treatment and have not had acute exacerbation within 1 year before screening are allowed to be enrolled. Patients with asthma requiring medical intervention with bronchodilators cannot be included.
• Patients with active pulmonary tuberculosis. Those who have received adequate treatment and have stopped anti-tuberculosis treatment for at least 3 months before treatment can be enrolled.
• Patients with uncontrolled clinical symptoms or diseases of the heart, such as: (1) New York Heart Association (NYHA) class 2 or higher heart failure (2) Unstable angina pectoris (3) Myocardial infarction within 1 year (4) Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
• Patients who have experienced severe infections within 1 month before the start of treatment, including but not limited to infections requiring hospitalization, bacteremia, severe pneumonia, etc.; patients with any active infections, or those with unexplained fever > 38.5°C during the screening period or before the first dose.
• Patients with a known positive history of human immunodeficiency virus (HIV) test or acquired immune deficiency syndrome (AIDS). Patients with active viral hepatitis (for hepatitis B: positive HBsAg and HBV DNA test value exceeds 500 IU; for hepatitis C: positive HCV antibody and HCV virus titer test value exceeds the upper limit of normal).
• Patients with known allergic reactions to adebiralimab or other PD-(L)1 monoclonal antibodies, or with a history of severe allergies to paclitaxel and platinum-based drugs or their prophylactic medications.
• Patients who have undergone major surgical procedures, systemic chemotherapy, immunotherapy, or other clinical trial drugs within 4 weeks before treatment; those who have received palliative radiotherapy within 2 weeks before treatment; those who have taken oral molecular targeted drugs and have stopped for less than 5 half-lives before treatment; or those who have used antibiotics within 1 week before treatment; and those who have not recovered from the toxicity and/or complications of previous interventions to NCI-CTCAE ≤ grade 1 (except for alopecia and fatigue, and the indicators mentioned in the inclusion criteria).
• According to the researcher's judgment, participants with other factors that may affect the research results or lead to the premature termination of this study, such as alcoholism, drug abuse, substance misuse, other serious diseases (including mental disorders) requiring combined treatment, severe laboratory test abnormalities, or those with family or social factors that may affect medication safety, will be excluded.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07479628 · IS26017

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗