Non-Small Cell Lung Cancer
Conditions
Keywords
Surgically Resectable, NSCLC, Nivolumab, FL-101, Placebo
Brief summary
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
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.
Interventions
DRUGFL-101
200 mg administered intravenously every 2 weeks prior to surgery.
DRUGNivolumab
240 mg administered intravenously every 2 weeks prior to surgery.
DRUGPlacebo
200 mg administered intravenously every 2 weeks prior to surgery.
Sponsors
Flame Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Cohort 2 will be randomized. The investigator and participants will be masked.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Previously untreated and pathologically confirmed, surgically resectable Stage IA3, IB, II, or IIIA NSCLC of squamous or non-squamous histology. 2. ≥1 radiologically measurable tumor \>2cm in diameter. 3. Smoking history ≥10 pack years. 4. Available tissue block for analysis from a core needle biopsy(or similar sample) 5. High-sensitivity C-reactive protein (hsCRP) level ≥2 mg/L
Exclusion criteria
1. Any prior exposure to chemotherapy, radiotherapy or systemic anti-cancer therapy (e.g., monoclonal antibody therapy) for lung cancer. 2. 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 3. 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. 4. Tumors known to express driver mutations of the EGFR or ALK pathways. 5. Known severe hypersensitivity (Grade ≥3) to FL-101, its active substance, or any of its excipients 6. Known history of human immunodeficiency virus or active Hepatitis B or Hepatitis C infection Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with treatment related adverse events as assessed by NCI CTCAE v.5.0 | From time of first dose to 3 months after surgery | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathologic Response | At time of surgery (around 6-8 weeks after first dose) | To determine major pathologic response (MPR), defined as ≤10 percent viable tumor |
| Number of patients with treatment efficacy as assessed by pathological response (percentage of residual tumor) by independent pathology review. | At time of surgery (around 6-8 weeks) | 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 |
| Complete Pathologic Response | At time of surgery (around 6-8 weeks after first dose) | To estimate complete pathologic response (CPR), defined as the absence of residual invasive cancer in resected lung specimens and lymph nodes |
| Objective Response Rate (ORR) | At time of surgery (around 6-8 weeks after first dose) | To estimate objective response rate (ORR) by RECIST 1.1 |
| MRD measurement by ctDNA | From time of first dose to 3 months after surgery | To describe the time course of minimal residual disease (MRD) response by ctDNA and recurrence in correlation with clinical response |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum hsCRP | From enrollment up to 3 months after surgery | To evaluate the effect of FL-101 on pharmacodynamic biomarkers |
| Prevalence and incidence of Anti-FL-101 antibodies | From time of first dose up to 3 months after surgery | To evaluate possible immunogenicity of FL-101 |
| Plasma IL-1β/IL-6 levels | From time of first dose up to 3 months after surgery | To evaluate the effect of FL-101 on pharmacodynamic biomarkers |
| Plasma Concentration of FL-101 | From time of first dose up to 3 months after surgery | To evaluate the pharmacokinetics of FL-101 in patients with NSCLC |
Outcome results
None listed