Using a blood test (ctDNA) to predict chemo‑immunotherapy response and find leftover cancer in non‑small cell lung cancer

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)

This trial will see if a blood test called ctDNA can predict how people with resectable non‑small cell lung cancer respond to chemo‑immunotherapy and whether giving pembrolizumab after surgery lowers the chance of the cancer coming back.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Miami (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, pembrolizumab
• Locations: 1 site (Miami, Florida)
• Trial ID: NCT06902272 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial will enroll adults with resectable stage IB (≥4 cm), II, or IIIB (N2) non‑small cell lung cancer who are planned for neoadjuvant platinum‑doublet chemotherapy with immunotherapy and subsequent surgery. Blood samples will be tested for circulating tumor DNA (ctDNA) before, during, and after treatment to see if ctDNA levels predict radiologic and pathologic response and to detect minimal residual disease (MRD). Participants who are ctDNA‑positive or have evidence of residual disease after standard treatment may receive adjuvant pembrolizumab to try to reduce recurrence. Tumor tissue is required for PD‑L1 testing and participants must have ECOG performance status 0–1 and measurable disease by RECIST 1.1.

Who should consider this trial

Good fit: Adults (≥18) with resectable stage IB [≥4 cm], II, or IIIB (N2) non‑small cell lung cancer planned for neoadjuvant chemo‑immunotherapy and surgery, with ECOG 0–1 and available tumor tissue for PD‑L1 testing, are ideal candidates.

Not a fit: Patients with metastatic or unresectable disease, poor performance status (ECOG >1), no measurable disease, or without available tumor tissue for PD‑L1 testing are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could let doctors use a simple blood test to tailor treatment and give additional immunotherapy to patients at higher risk of recurrence, potentially reducing relapses.

How similar studies have performed: Early results from other ctDNA MRD studies in NSCLC and other cancers have been promising for predicting recurrence, and adjuvant pembrolizumab has shown benefit in some resected NSCLC trials, but combining ctDNA‑directed adjuvant immunotherapy is still being explored.

Eligibility criteria

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 .

Where this trial is running

Miami, Florida

• University of Miami — Miami, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Richa Dawar, MD — University of Miami
• Study coordinator: Richa Dawar, MD

Conditions Non Small Cell Lung Cancer