Evaluation of Adjuvant Chemotherapy with Paclitaxel, Cisplatin, and Carboplatin in High-Risk Stage I/IIA Non-Squamous NSCLC Post-Resection

The primary objective of this study is to compare **disease-free survival (DFS)** in patients with completely resected (R0), stage I or IIA non-squamous non-small cell lung cancer (NSCLC) who are identified as high or intermediate risk by a 14-Gene Prognostic Assay. These patients are either randomized to observation or to initiate adjuvant therapy with four cycles of a standard NSCLC platinum-based doublet. This objective is clinically relevant as it aims to document the benefit of personalizing patient care based on molecular prognostic data, potentially improving patient outcomes by tailoring treatment strategies.

Secondary objectives include:

• Comparing DFS in patients randomized to each study arm without regard to actual initiation of chemotherapy (intention-to-treat population), and in patients who comply with observation and chemotherapy arm assignments and receive at least half of the intended chemotherapy course (per-protocol population).
• Comparing overall survival (OS) and time to recurrence (TTR) in patients randomized to each study arm.
• Further documenting the previously verified separation of survival curves among high- and low-risk patients identified by the 14-Gene Prognostic Assay in this prospective cohort of stage I or IIA non-squamous NSCLC patients.

The clinical trial involves a total of **615 participants** diagnosed with completely resected stage I or IIA non-squamous non-small cell lung cancer (**NSCLC**). The study population includes both male and female subjects, aged 18 years and older, who are considered to be at high or intermediate risk according to the 14-Gene Prognostic Assay. Participants were selected based on their ability to comply with the protocol, including eligibility for adjuvant chemotherapy and a life expectancy of at least five years, excluding the NSCLC diagnosis. The trial includes individuals with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The selection criteria also require participants to have a completely resected tumor with adequate tissue samples available for the prognostic assay. Lifestyle considerations such as the use of reliable contraception methods are required for both men and women of childbearing potential. The trial population is not limited to any specific lifestyle or dietary habits, but participants must be willing to be randomized to chemotherapy and comply with follow-up for the anticipated length of the study.

The clinical trial is designed as a **randomized**, prospective study to evaluate the efficacy of adjuvant chemotherapy in patients with completely resected stage I or IIA non-squamous non-small cell lung cancer (NSCLC) identified as high or intermediate risk by a 14-gene prognostic assay. The trial employs a **double-blind** methodology to ensure unbiased results, with participants being randomly assigned to either observation or adjuvant therapy with a standard NSCLC platinum-based doublet. The trial is expected to span approximately eight years, with an estimated end date of January 30, 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, including histologically documented complete resection and adequate tissue sample availability for the prognostic assay. Following randomization, participants will attend follow-up visits to monitor disease-free survival (DFS) and overall survival (OS), with the primary endpoint being the duration of DFS. The end-of-study visit will occur at the conclusion of the trial or upon early termination.

The expected length of participant involvement is up to five years from the initiation of enrollment, with conditions for early termination including disease recurrence, withdrawal of consent, or adverse events that preclude continued participation. The trial aims to document the benefit of personalizing patient care based on molecular prognostic data, with secondary endpoints including time to recurrence (TTR) and comparisons of DFS and OS in different risk groups. Participants will receive chemotherapy via **intravenous infusion**, with drugs such as **paclitaxel**, **cisplatin**, **carboplatin**, **vinorelbine tartrate**, **docetaxel**, and **pemetrexed** being administered according to the trial protocol.

The clinical trial involves the administration of several **experimental medications** as part of the treatment regimen for patients with completely resected stage I or IIA non-squamous non-small cell lung cancer. **Paclitaxel** is administered as a concentrate for solution for infusion. The maximum daily dose is 175 mg/m², with a total maximum dose of 700 mg/m² over a treatment period of 16 weeks. The route of administration is via **intravenous infusion**. Paclitaxel functions as a chemical antimicrotubule agent.

**Cisplatin** is also used in this trial, provided as a concentrate for solution for infusion. The maximum daily dose is 20 mg/m², with a total maximum dose of 80 mg/m² over the same 16-week period. It is administered through intravenous infusion and acts as a chemical antineoplastic agent.

**Carboplatin** is included in the treatment protocol, delivered as a solution for infusion. The maximum daily dose is 400 mg/m², with a total maximum dose of 1600 mg/m² over 16 weeks. Administration is via intravenous infusion, and it serves as a chemical antineoplastic agent.

**Vinorelbine tartrate** is administered as a concentrate for solution for infusion, with a maximum daily dose of 30 mg/m² and a total maximum dose of 120 mg/m² over the 16-week treatment period. The route of administration is intravenous infusion, and it functions as a chemical antineoplastic agent.

**Docetaxel** is provided as a concentrate for solution for infusion, with a maximum daily dose of 75 mg/m² and a total maximum dose of 300 mg/m² over 16 weeks. It is administered via intravenous infusion and acts as a chemical antineoplastic agent.

**Pemetrexed** is included in the trial as a concentrate for solution for infusion. The maximum daily dose is 500 mg/m², with a total maximum dose of 2000 mg/m² over the 16-week period. It is administered through intravenous infusion and functions as a chemical anti-cancer antifolate.

All medications are administered in a controlled clinical setting, with compliance monitored throughout the trial. The treatment regimen is designed to evaluate the efficacy of these agents in improving disease-free survival in the specified patient population. No non-experimental treatments, such as placebo or comparator treatments, are mentioned in the trial data provided.

The efficacy of the clinical trial will be assessed primarily through the evaluation of **disease-free survival (DFS)** in patients with completely resected stage I or IIA non-squamous non-small cell lung cancer (NSCLC) identified as high or intermediate risk by a 14-Gene Prognostic Assay. DFS is defined as the time from randomization to disease recurrence or death from any cause. Patients without events at the time of analysis will be censored at their last known event-free date. The primary efficacy analysis will focus on the modified intent-to-treat (mITT) population.

Secondary efficacy analyses will include the duration of DFS in the standard intent-to-treat (ITT) population and the per-protocol (PP) population. Additional secondary endpoints will assess overall survival (OS) and time to recurrence (TTR) in patients identified as high or intermediate risk by the 14-Gene Prognostic Assay. OS is defined as the time from randomization to death, with patients alive at the end of the analysis censored at their last known alive date. TTR is defined as the time from randomization until documented disease recurrence, with death as a competing risk. For TTR, recurrences first diagnosed at the time of death will be treated as recurrences at the date of death. Patients without documented recurrence will be censored at their last documented follow-up. These analyses will be conducted for the mITT, ITT, and PP populations.

An additional secondary endpoint involves comparing OS, DFS, and TTR in patients identified by the 14-Gene Prognostic Assay as high or intermediate risk stage I or IIA non-squamous NSCLC randomized to observation with those identified as low-risk. The trial is designed to document the benefit of personalizing patient care based on molecular prognostic data.