WAST Cell-Docetaxel Combination Therapy in PD-1 Inhibitor-Resistant Advanced NSCLC

Официальное название

Phase II Clinical Trial Evaluating Whole Agonist-Stimulated T (WAST) Cells in Combination With Docetaxel as a Second-line Treatment for Advanced Non-small Cell Lung Cancer (NSCLC) Resistant to PD-1 Inhibitors

Обзор

This prospective Phase II study aims to evaluate the preliminary efficacy and safety of WAST cells combined with docetaxel as second-line therapy in patients with advanced NSCLC resistant to PD-1 inhibitors.

Вмешательства

• Биопрепарат Whole Agonist-Stimulated T (WAST) cells injection
  WAST cells (≥4.0 × 10⁹ cells), intravenous infusion, d14, Q3W for 4 cycles.
• Препарат Docetaxel
  75 mg/m², intravenous infusion, day 1, Q3W.

Первичные конечные точки

• Objective Response Rate (ORR) [Срок оценки: Time Frame: Up to 24 months]

Вторичные конечные точки (5)

• Progression-free survival (PFS) [Срок оценки: up to 24 months]
• Overall Survival (OS) [Срок оценки: up to 3 years]
• Disease Control Rate (DCR) [Срок оценки: up to 24 months]
• Duration of response (DOR) [Срок оценки: up to 24 months]
• Number of Participants Who Experienced an Adverse Event (AE) [Срок оценки: up to 24 months (Serious AEs: Up to 90 days after last dose of study treatment (Other AEs: Up to 30 days after last dose of study treatment)]

Критерии участия

Критерии включения

• At screening, patients must meet the following diagnostic and treatment criteria: 1) Histologically or cytologically confirmed NSCLC, 2) Advanced NSCLC as determined by imaging according to AJCC V8, 3) Disease progression after first-line treatment with a PD-1 inhibitor; Expected survival time greater than 3 months;
• At screening, measurable target lesions on imaging with the longest diameter greater than 1.0 cm;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 at screening;
• Adequate bone marrow reserve at screening, defined as:

Absolute neutrophil count (ANC) >1.5×10⁹/L; Absolute lymphocyte count (ALC) ≥0.3×10⁹/L; Platelets (PLT) ≥100×10⁹/L; Hemoglobin (HGB) ≥100g/L;

• Adequate organ function at screening, meeting the following criteria:

Aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal (ULN) (≤5 ULN if due to tumor infiltration); Alanine aminotransferase (ALT) ≤2.5 times ULN (≤5 ULN if due to tumor infiltration); Total serum bilirubin ≤1.5 times ULN (≤3 ULN if due to tumor infiltration); Serum creatinine (Scr) ≤1.5 times ULN, or creatinine clearance rate ≥60 mL/min; Minimum lung reserve level, defined as ≤Grade 1 dyspnea and oxygen saturation >91% without supplemental oxygen; International Normalized Ratio (INR) ≤1.5 times ULN, and activated partial thromboplastin time (APTT) ≤1.5 times ULN;

• Women of childbearing potential must have a negative urine pregnancy test, and any male or female patient capable of having children must agree to use effective contraception throughout the study and for at least 1 year after the last dose of study treatment.

Критерии исключения

• Patients with symptomatic central nervous system (CNS) metastases at screening (patients with asymptomatic CNS metastases, or those who have been treated locally and are stable without symptoms for 4 weeks, are eligible);
• History of CNS disorders prior to screening, such as epilepsy, cerebrovascular ischemia/hemorrhage, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar diseases, organic brain syndromes, psychiatric disorders, or any autoimmune diseases affecting the CNS;
• Received immunotherapy, targeted therapy, chemotherapy, or radiotherapy within 4 weeks before screening, and deemed unsuitable for enrollment by the investigator;
• Discontinued systemic corticosteroid therapy less than 72 hours before cell infusion; however, physiological replacement doses of steroids (e.g., prednisone <10 mg/day or equivalent) are allowed;
• Any history of adoptive cell therapy prior to screening;
• History of organ/tissue transplantation prior to screening;
• Known active systemic autoimmune diseases under treatment prior to screening;
• At screening, meets any of the following criteria:

Hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg) positive; Hepatitis B e antibody (HBe-Ab) and/or hepatitis B core antibody (HBc-Ab) positive, with HBV-DNA copy numbers above the lower limit of quantification; Hepatitis C antibody (HCV-Ab) positive; Treponema pallidum antibody (TP-Ab) positive; HIV antibody test positive; EBV-DNA, CMV-DNA copy numbers above the lower limit of quantification;

• Undergone major surgery within 4 weeks prior to screening and deemed unsuitable for enrollment by the investigator;
• History of other malignancies within the past 2 years (except successfully treated non-melanoma skin cancer or in situ carcinoma);
• At screening, meets any of the following cardiac conditions:

Left ventricular ejection fraction (LVEF) ≤50% (by ECHO); New York Heart Association (NYHA) class III or IV congestive heart failure; Uncontrolled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) or pulmonary hypertension despite standard treatment; Myocardial infarction or cardiac surgery within 12 months prior to cell infusion; Clinically significant valvular heart disease;

• Tumor involvement of the atrium or ventricle at screening;
• History of pulmonary interstitial fibrosis or severe chronic obstructive pulmonary disease (COPD);
• Presence of clinical emergencies requiring urgent intervention due to tumor obstruction or compression (e.g., bowel obstruction or vascular compression) at screening;
• Active bleeding at screening;
• History of deep vein thrombosis or pulmonary embolism within 6 months prior to screening;
• Vaccinated with live vaccines within 6 weeks prior to screening;
• Active infection requiring treatment at screening;
• Participation in another interventional clinical study within 4 weeks prior to screening;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Tianjin Medical University Cancer Institute and Hospital — Тяньцзинь

Идентификаторы

NCT: NCT07330050 · E20251324

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗