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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: FL-101; Drug: Nivolumab; Drug: Placebo

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.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Exclusion 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
3. Known severe hypersensitivity (Grade ≥3) to nivolumab or chemotherapy agents or to any of their excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of FL-101	To evaluate the pharmacokinetics of FL-101 in patients with NSCLC	From time of first dose up to 3 months after surgery
Plasma IL-1β/IL-6 levels	To evaluate the effect of FL-101 on pharmacodynamic biomarkers	From time of first dose up to 3 months after surgery
Serum hsCRP	To evaluate the effect of FL-101 on pharmacodynamic biomarkers	From enrollment up to 3 months after surgery
Prevalence and incidence of Anti-FL-101 antibodies	To evaluate possible immunogenicity of FL-101	From time of first dose up to 3 months after surgery

Collaborators and Investigators

• Sponsor: Flame Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2021
• Primary Completion (Actual): December 22, 2021
• Study Completion (Actual): December 22, 2021

Study Registration Dates

• First Submitted: February 10, 2021
• First Submitted That Met QC Criteria: February 16, 2021
• First Posted (Actual): February 17, 2021

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: December 22, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: NSCLC; Nivolumab; Placebo; Surgically Resectable; FL-101
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: FL-101-2001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No