Surgically resectable non-small cell lung cancer MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10029517 Term: Non-small cell lung cancer stage I System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10029
Conditions
Interventions
Product Code: FL-101
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Anti-IL-1ß antibody, subclass IgG4
Current Sponsor code: FL-101
Concentration unit: mg milligram(s)
Concentration t
Sponsors
Flame Biosciences
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if ALL the following criteria apply: 1. Male and female patients =18 years of age. 2. Previously untreated and pathologically confirmed, surgically resectable Stage IA3, IB, II, or IIIA NSCLC of squamous or non-squamous histology. Staging is based on the eighth edition of the AJCC/UICC staging system. 3. =1 radiologically measurable tumor >2 cm in diameter, as defined by RECIST v1.1 (Eisenhauer 2009). 4. Lung function capacity capable of tolerating the proposed lung surgery. 5. Smoking history =10 pack years. 6. High-sensitivity C-reactive protein (hsCRP) level =2 mg/L 7. Adequate organ function as defined by ALL of the following: - Absolute neutrophil count (ANC) =1500/µL - Platelets =100,000 /µL - Hemoglobin =9 g/dL - AST/ALT =2.5× upper limit of normal (ULN) - Total serum bilirubin =1.5×ULN; patients with Gilbert’s disease: =3×ULN - Alkaline phosphatase =2.5×ULN - INR and aPTT =1.5×ULN unless the patient is on therapeutic anticoagulation - Serum creatinine =1.5×ULN OR Creatinine clearance =30 mL/min/1.73 m2 by Cockcroft-Gault estimation. The patient’s estimated CrCl will be calculated by the local laboratory (for eligibility purposes) using screening/baseline height (m), actual weight (kg), and serum creatinine: Males: CrCl = ((140 – age in years) × weight (kg))/72× serum creatinine (mg/dL) Females: CrCl = ((140 – age in years) × weight (kg) ×0.85)/72× serum creatinine (mg/dL) 8. Available tissue block for analysis from a core needle biopsy (or similar sample). -Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks are preferred) or at least 10 unstained slides, with an associated pathology report, for central testing. -Acceptable samples include core-needle biopsies for deep tumor tissue (minimum of 3 cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 2). 10. Men must agree to use contraception or practice abstinence as well as refrain from donating sperm during the treatment period and for =180 days after the last dose of study treatment. (Section 5.3). 11. Women may participate if not pregnant, not breastfeeding, and at least 1 of the following conditions apply: - Not a woman of childbearing potential (WOCBP) - WOCBP who agrees to follow contraceptive guidance (Section 5.3) during the treatment period and for at least 180 days after the last dose of study treatment. Female patients will be considered of non-reproductive potential (not a WOCBP) if they are either: (1) postmenopausal (defined as at least 12 months with no menses without an alternative medical cause. In women < 45 years of age, a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. OR (2) have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening OR (3) have a congenital or acquired condition that prevents childbearing. 12. Able and willing to comply with protocol-specified requirements and to provide written informed consent. Are the trial subjects under 18? no Number of subjec
Exclusion criteria
Exclusion criteria: 1. Any prior exposure to chemotherapy, radiotherapy, or systemic anti-cancer 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 (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score =6, and prostate specific antigen [PSA] =10 mg/mL, etc.) 3. Currently participating in, or has participated in, a trial of an investigational agent within 4 weeks prior to the first dose of trial treatment or 5 half-lives, whichever is longer, or without recovery of clinically significant toxicities from that therapy. 4. Any of the following tumor locations/types: a. NSCLC involving the superior sulcus. b. Large cell neuro-endocrine cancer. c. Sarcomatoid tumor. 5. Tumors known to express driver mutations of EGFR or ALK pathways. Patients whose driver mutation status is unknown may enroll in the study; tissue will be checked after enrollment. SAP will describe how patients found to have one of the 2 driver mutations will be handled. 6. History of non-infectious pneumonitis /interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease that requires steroids. 7. Had allogenic tissue/sold organ transplant. 8. Known severe hypersensitivity (Grade =3) to FL-101, its active substance, or any of its excipients. 9. Known history of human immunodeficiency virus (HIV) or active Hepatitis B or Hepatitis C infection. 10. Received radiotherapy within 2 weeks of start of study treatment. 11. Symptomatic herpes zoster within the past 30 days, a serious bacterial infection within the past 6 months or have had other recent or ongoing signs of infections 12. Received a live or attenuated vaccine within 30 days prior to the first dose of study treatment. 13. Clinically unstable disease in any organ system despite current therapy, including, but not limited to ongoing or active infection including tuberculosis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations. 14. Use of illicit drugs or excess intake of alcohol, based on the judgement of the investigator. Additional Criteria for Patients with Stage II and III Disease 1. Prior treatment with anti-PD-1, anti-CTLA-4, or anti-PD-L1 therapeutic antibody or pathway-targeting agents 2. 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. - Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a 1-time dose of dexamethasone for nausea) may be enrolled. - The use of inhaled corticosteroids for asthma / COPD and mineralocorticoids (e.g., fludrocortisone) for orthostatic hypotension or adrenocortical insufficiency is allowed. 3. Known severe hypersensitivity (Grade =3) to nivolumab or any of the study chemotherapy agents or to any of their excipients. 4. Active autoimmune disease that has required syst
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of FL-101 as monotherapy and in combination with nivolumab;Secondary Objective: Efficacy 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 To determine major pathologic response (MPR) rate To determine complete pathologic response (CPR) rate To estimate objective response rate (ORR) by RECIST 1.1 following neoadjuvant FL-101 To describe the time course of MRD response by ctDNA and recurrence in correlation with clinical response Pharmacologic (PK/ PD) To evaluate the PK of FL-101 in patients with NSCLC. To evaluate the effect of FL-101 on PD biomarkers. Safety To evaluate possible immunogenicity, anti-drug antibodies ;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: From time of first dose to 3 months after surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: Number of patients with treatment efficacy as assessed by pathological response (percentage of residual tumor) by independent pathology review Pharmacologic (PK/ PD): Estimates of the following FL-101 PK parameters: Cmax, Cmin, AUC0-t, AUC0-inf, CL, Vz, t½ Change from baseline in serum hsCRP, IL-6, and neutrophil / lymphocyte ratio. Change from baseline in plasma IL-1ß levels Safety: Prevalence and incidence of anti-FL-101 antibodies. ;Timepoint(s) of evaluation of this end point: At time of surgery (around 6-8 weeks after first dose) | — |
Countries
Canada, France, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Flame Biosciences
Outcome results
None listed