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

Phase 2

Not yet recruiting

• Conditions: Non Small Cell Lung Cancer
• Interventions: Diagnostic Test: Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay; Drug: Pembrolizumab; Drug: Platinum Doublet Chemotherapy

• Registration Number: NCT06902272
• Lead Sponsor: University of Miami

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-24
• Study First Submitted QC: 2025-03-24
• Last Update Submitted: 2025-03-24
• Study First Posted: 2025-03-30
• Last Update Posted: 2025-03-30
• Study Start: 2025-06-01
• Primary Completion: 2028-06-01
• Study Completion: 2029-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Eligible participants must be males or females ≥18 years of age on day of signing the informed consent form.

2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1

3. 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

4. Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

5. 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:

   1. 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
   2. 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.

Exclusion Criteria

1. 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).
2. Participants with known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) translocation
3. Previous exposure to anti-cancer therapy, including chemotherapy, radiotherapy or immunotherapy, and previous exposure to immunosuppressive drugs within 3 weeks before neoadjuvant treatment
4. Participants with impaired decision-making capacity .

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ctDNA Monitoring Group	Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay	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.
ctDNA Monitoring Group	Platinum Doublet Chemotherapy	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.
ctDNA Monitoring Group	Pembrolizumab	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.

Primary Outcome Measures

Name	Time	Method
Change in ctDNA Clearance: Neoadjuvant Phase Measured by Percentage of Participants	Baseline, 3 months	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.
Pathologic Complete Response (pCR) As Measured By Percentage of Participants	Up to 3 months	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.

Secondary Outcome Measures

Name	Time	Method
Recurrence-free survival (RFS)	Up to 2.5 years	Recurrence-free survival (RFS) is the elapsed time in months from the date of surgery until the first documented date of local recurrence, distant relapses (recurrence will be assessed by imaging; distant relapses will be assessed by imaging), or death from any cause, whichever is earlier. For alive patients without recurrence/relapse, follow-up time will be censored at the last documented date of disease assessment.
Overall survival (OS)	Up to 2.5 years	Overall survival (OS)is the elapsed time in months from the date of surgery until the date of death. For alive patients, follow-up time will be censored at the last date known to be alive.
Percentage of Participants Achieving ctDNA Clearance: Adjuvant Phase	Up to 1.5 years	ctDNA clearance is defined as detectable ctDNA at start of adjuvant treatment to no detectable ctDNA during the post-operative period. The percentage of participants experiencing ctDNA clearance will be reported.
Percentage of Participants With ctDNA Recurrence: Adjuvant Phase	Up to 1.5 years	ctDNA recurrence is defined as no detectable ctDNA at the start adjuvant treatment initiation to detectable ctDNA during the post-operative period. The percentage of participants with ctDNA recurrence will be reported.

Trial Locations

Locations (1)

University of Miami; 🇺🇸 Miami, Florida, United States