PROPHET Study: ctDNA-Guided Personalized Induction Immunochemotherapy for NSCLC

Sun Yat-sen University

Status and phase: Enrolling; Phase 2

Conditions: Non-small Cell Lung Cancer (NSCLC)

Treatments: Drug: PD-1 inhibitor; Drug: Platinum Doublet

Study type: Interventional

Funder types: Other

Identifiers

NCT06977074

B2025-176-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 83 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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83 participants in 1 patient group

Induction immunochemotherapy

Experimental group

Treatment:

Drug: Platinum Doublet

Drug: PD-1 inhibitor