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

Sponsor

Flame Biosciences (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT04758949

Collaborator

(none)

Enrollment

Arms

3.9

Actual Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: FL-101 Drug: Nivolumab Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

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

Official Title:

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

Actual Study Start Date :

Aug 25, 2021

Actual Primary Completion Date :

Dec 22, 2021

Actual Study Completion Date :

Dec 22, 2021

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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
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
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 Outcome Measures

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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.