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)
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- University of Miami
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Change in ctDNA Clearance: Neoadjuvant Phase Measured by Percentage of Participants
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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 .
Arms & Interventions
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.
Intervention: Platinum Doublet Chemotherapy (Drug)
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.
Intervention: Circulating Tumor Deoxyribonucleic acid (ctDNA) Assay (Diagnostic Test)
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.
Intervention: Pembrolizumab (Drug)
Outcomes
Primary Outcomes
Change in ctDNA Clearance: Neoadjuvant Phase Measured by Percentage of Participants
Time Frame: 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
Time Frame: 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 Outcomes
- 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)
Investigators
Richa Dawar, MD
Medical Doctor, Oncology
University of Miami