Clinical trial NCT06902272: ctDNA to Predict Response to Chemo-Immunotherapy and Detect Minimal Residual Disease in Non-Small Cell Lung Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2025-03-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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 .

Primary outcomes:
measure: Change in ctDNA Clearance: Neoadjuvant Phase Measured by Percentage of Participants
timeFrame: Baseline, 3 months
measure: Pathologic Complete Response (pCR) As Measured By Percentage of Participants
timeFrame: Up to 3 months
Secondary outcomes:
measure: Recurrence-free survival (RFS)
timeFrame: Up to 2.5 years
measure: Overall survival (OS)
timeFrame: Up to 2.5 years
measure: Percentage of Participants Achieving ctDNA Clearance: Adjuvant Phase
timeFrame: Up to 1.5 years
measure: Percentage of Participants With ctDNA Recurrence: Adjuvant Phase
timeFrame: Up to 1.5 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Richa Dawar, MD
role: PRINCIPAL_INVESTIGATOR
References: