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

Phase 2RecruitingNCT06902272

University of Miami30 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non Small Cell Lung Cancer

Interventions

Circulating Tumor Deoxyribonucleic acid (ctDNA) AssayDIAGNOSTIC_TEST

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.

PembrolizumabDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 .

Locations (1)

University of Miami

Miami, Florida, United States

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Up to 3 months

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 1.5 years

Central Contacts

Richa Dawar, MD

CONTACT

(954) 461-2107 richa.dawar@med.miami.edu

Data from ClinicalTrials.gov

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