ctDNA to Predict Response to Chemo-Immunotherapy and Detect Minimal Residual Disease in Non-Small Cell Lung Cancer

NCT06902272 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20240140
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if a blood test called circulating tumor DNA (ctDNA) can be used to predict how well patients will respond to treatment and if there is any cancer left after surgery. The investigators will also study if a drug called pembrolizumab can help prevent the cancer from coming back in patients who are ctDNA-positive or who have evidence of cancer after treatment and surgery.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Change in ctDNA Clearance: Neoadjuvant Phase Measured by Percentage of Participants

  ctDNA clearance is defined as change from detectable ctDNA at start of neoadjuvant treatment to no detectable ctDNA at the end of neoadjuvant treatment or prior to surgery. The percentage of participants experiencing ctDNA clearance will be reported.

  Baseline, 3 months

• Pathologic Complete Response (pCR) As Measured By Percentage of Participants

  Pathologic Complete Response (pCR) is defined as percentage of participants who underwent surgery after neoadjuvant therapy with 0% viable tumor in resected lung and lymph nodes.

  Up to 3 months

Secondary Outcomes (4)

• Recurrence-free survival (RFS)

  Up to 2.5 years

• Overall survival (OS)

  Up to 2.5 years

• Percentage of Participants Achieving ctDNA Clearance: Adjuvant Phase

  Up to 1.5 years

• Percentage of Participants With ctDNA Recurrence: Adjuvant Phase

  Up to 1.5 years

Study Arms (1)

ctDNA Monitoring Group

EXPERIMENTAL

Participants in this group will receive ctDNA monitoring in combination with standard of care (SOC) Pembrolizumab, SOC platinum doublet chemotherapy, and SOC surgery for resection of tumor. Total participation duration is up to 2.5 years.

Diagnostic Test: Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay; Drug: Pembrolizumab; Drug: Platinum Doublet Chemotherapy

Interventions

Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay DIAGNOSTIC_TEST

ctDNA will be measured in participants in person via blood samples during Screening/Baseline and at the following intervals during treatment and follow-up: * During Neoadjuvant Therapy: Approximately once after four cycles of standard of care Pembrolizumab and platinum doublet therapy. * Approximately once two weeks before surgery. * Approximately once three weeks after surgery. * During Adjuvant Therapy: Approximately once every 12 weeks during standard of care, adjuvant Pembrolizumab therapy. * Follow-up Period: Approximately once every three months for up to one year.

ctDNA Monitoring Group

Pembrolizumab DRUG

Participants will receive standard of care, neoadjuvant Pembrolizumab therapy intravenously (IV) on Day 1 of each three-week cycle, for up to four cycles prior to standard of care surgery. After surgery, low-risk participants may continue standard of care, adjuvant Pembrolizumab therapy for up to six months; high-risk participants may receive standard of care, adjuvant Pembrolizumab therapy for up to 12 months.

ctDNA Monitoring Group

Platinum Doublet Chemotherapy DRUG

Participants will receive neoadjuvant platinum doublet chemotherapy intravenously (IV) per standard of care on Day 1 of each three-week cycle for up to four cycles, prior to standard of care surgery. Possible platinum doublet chemotherapy regimens are Cisplatin/Carboplatin in combination with Pemetrexed or Docetaxel or Gemcitabine. Participants receiving Gemcitabine therapy will be administered Gemcitabine, per standard of care, on Day 8 of each three-week cycle.

ctDNA Monitoring Group

Eligibility Criteria

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

You may qualify if:

• Eligible participants must be males or females ≥18 years of age on day of signing the informed consent form.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
• Participants with histologically confirmed Stage IB (≥4 cm), II, or IIIB (N2) NSCLC (as per the 8th American Joint Committee on Cancer (AJCC)) who are considered resectable by a multidisciplinary team and who are going to be treated with neoadjuvant treatment including chemotherapy, immunotherapy, and in some cases radiation before surgery
• Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
• Participants must have tumor tissue available for programmed cell death ligand 1 (PD-L1) immunohistochemical (IHC) testing performed by a third-party analyzing lab during the screening period:
• Either a formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections, with an associated pathology report, must be submitted for biomarker evaluation prior to randomization. The tumor tissue sample may be fresh or archival if obtained within 6 months prior to enrollment
• Tissue must be a core needle biopsy, excisional or incisional biopsy. Fine needle biopsies obtained by endobronchial ultrasound (EBUS) are not considered adequate for biomarker review and randomization. Core needle biopsies obtained by EBUS are acceptable for randomization.

You may not qualify if:

• Presence of locally advanced, unresectable, or metastatic disease. Mediastinal lymph node samples at levels 4 (bilaterally) and 7 are required for clinical staging to assess nodal involvement in participants with mediastinal adenopathy on positron emission tomography-computed tomography scan (PET/CT).
• Participants with known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) translocation
• Previous exposure to anti-cancer therapy, including chemotherapy, radiotherapy or immunotherapy, and previous exposure to immunosuppressive drugs within 3 weeks before neoadjuvant treatment
• Participants with impaired decision-making capacity .

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Richa Dawar, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richa Dawar, MD

CONTACT

(954) 461-2107; richa.dawar@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Oncology

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: March 30, 2025
• Study Start: June 11, 2025
• Primary Completion (Estimated): June 11, 2028
• Study Completion (Estimated): June 11, 2029
• Last Updated: July 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)