PROPHET Study: ctDNA-Guided Personalized Induction Immunochemotherapy for NSCLC

Phase 2

Recruiting

• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Interventions: Drug: PD-1 inhibitor; Drug: Platinum Doublet

• Registration Number: NCT06977074
• Lead Sponsor: Sun Yat-sen University

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.

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-01
• Study Start: 2025-05-10
• Study First Submitted QC: 2025-05-10
• Last Update Submitted: 2025-05-10
• Study First Posted: 2025-05-16
• Last Update Posted: 2025-05-16
• Primary Completion: 2028-05-10
• Study Completion: 2030-05-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 83

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Induction immunochemotherapy	PD-1 inhibitor	-
Induction immunochemotherapy	Platinum Doublet	-

Primary Outcome Measures

Name	Time	Method
MPR	From date of enrollment until one month after resection	MPR is defined as ≤10% residual viable tumor in the resected specimen

Secondary Outcome Measures

Name	Time	Method
R0 resection rate	From date of enrollment to an average of 18 weeks after the first dose	defined as the percentage of patients that undergo R0 surgical resection after neoadjuvant treatment
pCR rate	From date of enrollment until one month after resection	PCR rate is defined the percentage of patients with no residual viable tumor in the resected specimen
24-month EFS	36 months following initial treatment	24-month event-free survival rate in ITT population, defined as the interval between the start of neoadjuvant treatment and any progression of disease precluding surgical resection, progression of disease in the absence of surgery, progression or recurrence after surgery, or death from any cause, whichever occurred first

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China