PROPHET Study: ctDNA-Guided Personalized Induction Immunochemotherapy for NSCLC

NCT06977074 | Recruiting Phase 2 DMC

• 1 other identifier: B2025-176-01
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Keywords

Non-small cell lung cancer; ctDNA; Induction therapy; Immunochemotherapy

Outcome Measures

Primary Outcomes (1)

• MPR

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

  From date of enrollment until one month after resection

Secondary Outcomes (3)

• R0 resection rate

  From date of enrollment to an average of 18 weeks after the first dose

• pCR rate

  From date of enrollment until one month after resection

• 24-month EFS

  36 months following initial treatment

Other Outcomes (1)

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

  3 months following resection

Study Arms (1)

Induction immunochemotherapy

EXPERIMENTAL

Drug: PD-1 inhibitor; Drug: Platinum Doublet

Interventions

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

Induction immunochemotherapy

Platinum Doublet DRUG

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

Induction immunochemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Ting Zhou

  Sun Yat-sen University

  STUDY CHAIR

Central Study Contacts

Ze-Rui Zhao, MD PhD

CONTACT

+86 87343317; zhaozr@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Ze-Rui Zhao

Study Record Dates

• First Submitted: May 1, 2025
• First Posted: May 16, 2025
• Study Start: May 10, 2025
• Primary Completion (Estimated): May 10, 2028
• Study Completion (Estimated): May 10, 2030
• Last Updated: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)