Clinical trial NCT06977074: PROPHET Study: ctDNA-Guided Personalized Induction Immunochemotherapy for NSCLC
Official title: Prospective Phase II Proof-of-Concept Trial on Circulating Tumor DNA (ctDNA)-Optimized Induction Immunochemotherapy Cycle Reduction for Resectable Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer (NSCLC)
Keywords: Non-small cell lung cancer
ctDNA
Induction therapy
Immunochemotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2025-05-16
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: MPR
timeFrame: From date of enrollment until one month after resection
Secondary outcomes:
measure: R0 resection rate
timeFrame: From date of enrollment to an average of 18 weeks after the first dose
measure: pCR rate
timeFrame: From date of enrollment until one month after resection
measure: 24-month EFS
timeFrame: 36 months following initial treatment
Other outcomes:
measure: Efficacy and safety comparisons between 2-cycle vs. >2-cycle groups
timeFrame: 3 months following resection
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Ting Zhou
role: STUDY_CHAIR
References: