PROPHET Study: ctDNA-Guided Personalized Induction Immunochemotherapy for NSCLC

Официальное название

Prospective Phase II Proof-of-Concept Trial on Circulating Tumor DNA (ctDNA)-Optimized Induction Immunochemotherapy Cycle Reduction for Resectable Non-Small Cell Lung Cancer

Обзор

The goal of this clinical trial is to evaluate the clinical value of ctDNA testing in guiding the optimization of immunochemotherapy cycles during induction treatment for resectable patients with NSCLC. The main questions it aims to answer are: * Does ctDNA clearance indicate pathological complete response? * Are additional cycles of immunochemotherapy necessary for patients who have ctDNA clearance after initial cycles of treatment? Researchers will use ctDNA dynamics to guide the cycles of induction treatment to see if some patients can avoid excessive cycles of treatment.

Подробное описание

Advances in precision medicine have highlighted the potential of circulating tumor DNA (ctDNA) detection in NSCLC diagnosis, treatment efficacy monitoring, and prognosis evaluation. Induction immunotherapy combined with chemotherapy is now a standard treatment for patients with resectable NSCLC, but optimizing the number of immunochemotherapy cycles to enhance efficacy and reduce toxicity remains a critical clinical challenge. In this Phase II, proof-of-concept trial, around 83 patients with AJCC stage IIA-IIIB NSCLCs who are deemed resectable by an MDT team will participate to evaluate the potential role of dynamic ctDNA changes in guiding the cycle reduction of induction immunotherapy combined with chemotherapy while maintaining overall efficacy.

Eligible patients will receive 2 cycles (21-day intervals) of PD-1 inhibitor + platinum-based chemotherapy. Subsequent cycles (1-2 additional cycles) are determined by ctDNA status via tumour-agnostic strategies:

1. For patients with ctDNA clearance: Randomized (1:1) to surgery or continued therapy. 2. For patients with ctDNA persistence: Sequential 1-2 additional cycles. For all patients who are available to undergo surgery, the operation will be performed 4-6 weeks following the last cycle of treatment.

Вмешательства

• Препарат PD-1 inhibitor
  Two to four cycles of tislelizumab at a dose of 200 mg every three weeks, along with a platinum-based chemotherapy doublet based on the result of ctDNA dynamics
• Препарат Platinum Doublet
  Platinum-based chemotherapy (carboplatin AUC=5 + pemetrexed 500 mg/m² \[adenocarcinoma\] or nab-paclitaxel 260 mg/m² \[squamous/other subtypes\])

Первичные конечные точки

• MPR [Срок оценки: From date of enrollment until one month after resection]

Вторичные конечные точки (3)

• R0 resection rate [Срок оценки: From date of enrollment to an average of 18 weeks after the first dose]
• pCR rate [Срок оценки: From date of enrollment until one month after resection]
• 24-month EFS [Срок оценки: 36 months following initial treatment]

Критерии участия

Критерии включения

• Histologically/cytologically confirmed, untreated stage IIA-IIIB NSCLC (IASLC 8th edition).
• Deemed resectable by MDT.
• EGFR/ALK wild-type (non-squamous patients; squamous patients exempt).
• ECOG PS 0-1.
• Adequate organ function (neutrophils ≥1.5×10⁹/L, platelets ≥100×10⁹/L, Hb >9 g/dL, Cr ≤1.5×ULN, AST/ALT ≤3×ULN).
• Measurable lesions (RECIST 1.1).

Критерии исключения

• Active autoimmune diseases (exceptions: vitiligo, type I diabetes, stable hypothyroidism).
• Systemic corticosteroids (>10 mg prednisone equivalent/day) within 14 days.
• Grade 3-4 interstitial lung disease.
• Concurrent malignancies requiring treatment.
• Prior anti-PD-1/PD-L1/CTLA-4 therapy.
• Active HBV/HCV, HIV/AIDS, or pregnancy.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sun Yat-sen University Cancer Center — Гуанчжоу

Идентификаторы

NCT: NCT06977074 · B2025-176-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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