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

A Phase 2 Study of Circulating Tumor DNA to Predict Response to Neoadjuvant Treatment and De-escalation Adjuvant Immunotherapy in Early-Stage NSCLC (DNA-PREDICT)

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.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Diagnostic test: Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay; Drug: Pembrolizumab; Drug: Platinum Doublet Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Richa Dawar, MD; Phone Number: (954) 461-2107; Email: richa.dawar@med.miami.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Principal Investigator: Richa Dawar, MD
      • Contact: Richa Dawar, MD; Phone Number: (954) 461-2107; Email: richa.dawar@med.miami.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ctDNA Monitoring Group; 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; 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.; Drug: Pembrolizumab; 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.; Drug: Platinum Doublet Chemotherapy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival (RFS)	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.	Up to 2.5 years
Overall survival (OS)	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.	Up to 2.5 years
Percentage of Participants Achieving ctDNA Clearance: Adjuvant Phase	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.	Up to 1.5 years
Percentage of Participants With ctDNA Recurrence: Adjuvant Phase	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.	Up to 1.5 years

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Richa Dawar, MD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2025
• Primary Completion (Estimated): June 11, 2028
• Study Completion (Estimated): June 11, 2029

Study Registration Dates

• First Submitted: March 24, 2025
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): March 30, 2025

Study Record Updates

• Last Update Posted (Actual): July 22, 2025
• Last Update Submitted That Met QC Criteria: July 17, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: 20240140

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No