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

• ClinicalTrials.gov Identifier: NCT04758949
• Recruitment Status: Withdrawn
• First Posted: February 17, 2021
• Last Update Posted: January 11, 2022
• Sponsor: Flame Biosciences
• Information provided by (Responsible Party): Flame Biosciences

Tracking Information

• First Submitted Date: February 10, 2021
• First Posted Date: February 17, 2021
• Last Update Posted Date: January 11, 2022
• Actual Study Start Date: August 25, 2021
• Actual Primary Completion Date: December 22, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 17, 2021)

Number of patients with treatment related adverse events as assessed by NCI CTCAE v.5.0 [ Time Frame: 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.

Original Primary Outcome Measures (submitted: February 16, 2021)

• Pathologic Reponse following FL-101 neoadjuvant monotherapy [ Time Frame: At time of surgery (around 6-8 weeks after first dose) ]
  To evaluate pathological response (% residual tumor) in patients with Stage IA3, IB, or IC NSCLC
• Pathologic Response following FL-101 neoadjuvant combination therapy [ Time Frame: At time of surgery (around 6-8 weeks after first dose) ]
  To evaluate pathological response (% residual tumor) in patients with Stage II-IIIA NSCLC

Current Secondary Outcome Measures (submitted: May 17, 2021)

• Number of patients with treatment efficacy as assessed by pathological response (percentage of residual tumor) by independent pathology review. [ Time Frame: 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
• Major Pathologic Response [ Time Frame: At time of surgery (around 6-8 weeks after first dose) ]
  To determine major pathologic response (MPR), defined as ≤10 percent viable tumor
• Complete Pathologic Response [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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

Original Secondary Outcome Measures (submitted: February 16, 2021)

• Major Pathologic Response [ Time Frame: At time of surgery (around 6-8 weeks after first dose) ]
  To estimate major pathologic response (MPR), defined as ≤10% viable tumor
• Complete Pathologic Response [ Time Frame: 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) [ Time Frame: At time of surgery (around 6-8 weeks after first dose) ]
  To estimate objective response rate (ORR) by RECIST 1.1
• Disease Free Survival [ Time Frame: From date of first dose of study drug up to 130 weeks. ]
  To describe disease free survival
• Overall Survival [ Time Frame: From the start of dosing up to130 weeks. ]
  To describe overall survival

Current Other Pre-specified Outcome Measures (submitted: May 17, 2021)

• Plasma Concentration of FL-101 [ Time Frame: From time of first dose up to 3 months after surgery ]
  To evaluate the pharmacokinetics of FL-101 in patients with NSCLC
• Plasma IL-1β/IL-6 levels [ Time Frame: From time of first dose up to 3 months after surgery ]
  To evaluate the effect of FL-101 on pharmacodynamic biomarkers
• Serum hsCRP [ Time Frame: 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 [ Time Frame: From time of first dose up to 3 months after surgery ]
  To evaluate possible immunogenicity of FL-101

Original Other Pre-specified Outcome Measures (submitted: February 16, 2021)

• Plasma Concentration of FL-101 [ Time Frame: From time of first dose to 30 days after last dose (up to 82 weeks) ]
  To evaluate the pharmacokinetics of FL-101 in patients with NSCLC
• Plasma IL-1β levels [ Time Frame: From enrollment up to 82 weeks ]
  To evaluate the effect of FL-101 on pharmacodynamic biomarkers
• Serum hsCRP and IL-6 [ Time Frame: From enrollment up to 82 weeks ]
  To evaluate the effect of FL-101 on pharmacodynamic biomarkers
• AEs/SAEs [ Time Frame: From enrollment up to 82 weeks ]
  To evaluate the safety and tolerability of FL-101 as monotherapy and in combination with nivolumab.
• Anti-FL-101 antibodies [ Time Frame: From time of first dose up to 82 weeks ]
  To evaluate possible immunogenicity of FL-101

Descriptive Information

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

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Cohort 2 will be randomized. The investigator and participants will be masked.

Primary Purpose: Treatment

• Condition: Non-Small Cell Lung Cancer

Intervention

• 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.
• Drug: Placebo
  200 mg administered intravenously every 2 weeks prior to surgery.

Study Arms

• Experimental: FL-101 Monotherapy
  30 patients will receive FL-101 prior to surgery.
  Intervention: Drug: FL-101
• Experimental: FL-101 + Nivolumab
  30 patients will receive FL-101 and Nivolumab prior to surgery.
  Interventions:

  • Drug: FL-101
  • Drug: Nivolumab
• Active Comparator: Nivolumab + Placebo
  30 patients will receive Nivolumab and placebo prior to surgery.
  Interventions:

  • Drug: Nivolumab
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: December 22, 2021): 0
• Original Estimated Enrollment (submitted: February 16, 2021): 180
• Actual Study Completion Date: December 22, 2021
• Actual Primary Completion Date: December 22, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Canada, France, Netherlands, United States

Administrative Information

• NCT Number: NCT04758949
• Other Study ID Numbers: FL-101-2001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Flame Biosciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Flame Biosciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Cassandra Choe-Juliak, MD; Flame Biosciences

• PRS Account: Flame Biosciences
• Verification Date: December 2021