FL-101 in Surgically Resectable Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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Phase 2 trial to study FL-101 alone or in combination with nivolumab in patients who have surgically resectable Non-Small Cell Lung Cancer.

Detailed Description
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A 2-Cohort, Phase 2, multicenter, parallel-design trial that will study patients with surgically resectable, stages I-IIIA, non-small cell lung cancer (NSCLC) . The clinical study will focus on whether FL-101 has direct anti-tumor activity when given alone prior to surgery, and if FL-101 improves the anti-tumor response when given in combination with nivolumab prior to surgery.

Official Title
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A Two-cohort, Phase 2 Study of FL-101 as Neoadjuvant Therapy in Patients With Surgically Resectable Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: FL-101
* Drug: Nivolumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated and pathologically confirmed, surgically resectable Stage IA3, IB, II, or IIIA NSCLC of squamous or non-squamous histology. ≥1 radiologically measurable tumor >2cm in diameter. Smoking history ≥10 pack years. Available tissue block for analysis from a core needle biopsy(or similar sample) High-sensitivity C-reactive protein (hsCRP) level ≥2 mg/L Exclusion Criteria: Any prior exposure to chemotherapy, radiotherapy or systemic anti-cancer therapy (e.g., monoclonal antibody therapy) for lung cancer. Malignancies other than NSCLC within 2 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome Currently participating in, or has participated in, a trial of an investigational agent within 4 weeks prior to the first dose of study treatment or 5 half-lives, whichever is longer and with recovery of clinically significant toxicities from that therapy. Tumors known to express driver mutations of the EGFR or ALK pathways. Known severe hypersensitivity (Grade ≥3) to FL-101, its active substance, or any of its excipients Known history of human immunodeficiency virus or active Hepatitis B or Hepatitis C infection Additional Exclusion Criteria for Patients with Stage II and III Disease Prior treatment with anti-PD-1, anti-CTLA-4, or anti-PD-L1 therapeutic antibody or pathway-targeting agents Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1 Known severe hypersensitivity (Grade ≥3) to nivolumab or chemotherapy agents or to any of their excipients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FL-101 Monotherapy<br>30 patients will receive FL-101 prior to surgery. | Drug: FL-101<br>* 200 mg administered intravenously every 2 weeks prior to surgery.<br>|
| Experimental: FL-101 + Nivolumab<br>30 patients will receive FL-101 and Nivolumab prior to surgery. | Drug: FL-101<br>* 200 mg administered intravenously every 2 weeks prior to surgery.<br>Drug: Nivolumab<br>* 240 mg administered intravenously every 2 weeks prior to surgery.<br>|
| Active Comparator: Nivolumab + Placebo<br>30 patients will receive Nivolumab and placebo prior to surgery. | Drug: Nivolumab<br>* 240 mg administered intravenously every 2 weeks prior to surgery.<br>Drug: Placebo<br>* 200 mg administered intravenously every 2 weeks prior to surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with treatment related adverse events as assessed by NCI CTCAE v.5.0 | To evaluate the tolerability, incidence and severity of AEs and SAEs graded according to NCI CTCAE v5.0 of FL-101 as monotherapy and in combination with nivolumab. | From time of first dose to 3 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with treatment efficacy as assessed by pathological response (percentage of residual tumor) by independent pathology review. | Cohort 1: To evaluate the activity of FL-101 neoadjuvant monotherapy in patients with Stage IA3 or IB NSCLC Cohort 2: To evaluate the effect of FL-101 in combination with nivolumab compared to nivolumab plus placebo in neoadjuvant therapy in patients with Stage II-IIIA NSCLC | At time of surgery (around 6-8 weeks) | 
| Major Pathologic Response | To determine major pathologic response (MPR), defined as ≤10 percent viable tumor | At time of surgery (around 6-8 weeks after first dose) | 
| Complete Pathologic Response | To estimate complete pathologic response (CPR), defined as the absence of residual invasive cancer in resected lung specimens and lymph nodes | At time of surgery (around 6-8 weeks after first dose) | 
| Objective Response Rate (ORR) | To estimate objective response rate (ORR) by RECIST 1.1 | At time of surgery (around 6-8 weeks after first dose) | 
| MRD measurement by ctDNA | To describe the time course of minimal residual disease (MRD) response by ctDNA and recurrence in correlation with clinical response | From time of first dose to 3 months after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surgically Resectable, NSCLC, Nivolumab, FL-101, Placebo