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)

Overview

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.

Interventions

• 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.
• 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.

Primary outcome measures

• Change in ctDNA Clearance: Neoadjuvant Phase Measured by Percentage of Participants [Time frame: Baseline, 3 months]
• Pathologic Complete Response (pCR) As Measured By Percentage of Participants [Time frame: Up to 3 months]

Secondary outcome measures (4)

• Recurrence-free survival (RFS) [Time frame: Up to 2.5 years]
• Overall survival (OS) [Time frame: Up to 2.5 years]
• Percentage of Participants Achieving ctDNA Clearance: Adjuvant Phase [Time frame: Up to 1.5 years]
• Percentage of Participants With ctDNA Recurrence: Adjuvant Phase [Time frame: Up to 1.5 years]

Eligibility criteria

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 .

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Miami — Miami

Identifiers

NCT: NCT06902272 · 20240140

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗