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NCT Number: NCT06977074

PROPHET Study: ctDNA-Guided Personalized Induction Immunochemotherapy for NSCLC

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.

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Key information

Conditions

Non-small Cell Lung Cancer (NSCLC) Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location status: Recruiting

Location contact

Ze-Rui Zhao

CONTACT

[email protected]

+86 87343317

About this study

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:

  • For patients with ctDNA clearance: Randomized (1:1) to surgery or continued therapy.
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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).

Exclusion criteria

  • 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.

Treatment and study plan

PD-1 inhibitor

Drug

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

Platinum Doublet

Drug

Platinum-based chemotherapy (carboplatin AUC=5 + pemetrexed 500 mg/m² [adenocarcinoma] or nab-paclitaxel 260 mg/m² [squamous/other subtypes])

Primary outcomes

  1. MPR

    Time frame: From date of enrollment until one month after resection

    MPR is defined as ≤10% residual viable tumor in the resected specimen

Secondary outcomes

  1. R0 resection rate

    Time frame: 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

  2. pCR rate

    Time frame: 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

  3. 24-month EFS

    Time frame: 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

Other outcomes

  1. Efficacy and safety comparisons between 2-cycle vs. >2-cycle groups

    Time frame: 3 months following resection

    Efficacy (MPR, pCR [percentages]) and safety (TRAEs [percentage]) comparisons between 2-cycle vs. >2-cycle groups.

Study contacts

Contact information is provided by the study sponsor or research team.

Ze-Rui Zhao, MD PhD

CONTACT

[email protected]

+86 87343317

Sponsors and collaborators

Lead sponsor

Sun Yat-sen University

Other

Registry information

Official study 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

Acronym: PROPHET

Important dates

Study start
2025
Primary completion
2028
Study completion
2030
First posted
May 16, 2025
Registry last updated
May 23, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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