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

Primary Purpose

Non-Small Cell Lung Cancer

Status

Withdrawn

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

FL-101

Nivolumab

Placebo

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring Surgically Resectable, NSCLC, Nivolumab, FL-101, Placebo

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

FL-101 Monotherapy

FL-101 + Nivolumab

Nivolumab + Placebo

Arm Description

30 patients will receive FL-101 prior to surgery.

30 patients will receive FL-101 and Nivolumab prior to surgery.

30 patients will receive Nivolumab and placebo prior to surgery.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Major Pathologic Response

To determine major pathologic response (MPR), defined as ≤10 percent viable tumor

Complete Pathologic Response

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)

To estimate objective response rate (ORR) by RECIST 1.1

MRD measurement by ctDNA

To describe the time course of minimal residual disease (MRD) response by ctDNA and recurrence in correlation with clinical response

Full Information

NCT ID

NCT04758949

First Posted

February 10, 2021

Last Updated

December 22, 2021

Sponsor

Flame Biosciences

1. Study Identification

Unique Protocol Identification Number

NCT04758949

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Withdrawn

Why Stopped

Sponsor Decision

Study Start Date

August 25, 2021 (Actual)

Primary Completion Date

December 22, 2021 (Actual)

Study Completion Date

December 22, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Flame Biosciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Small Cell Lung Cancer

Keywords

Surgically Resectable, NSCLC, Nivolumab, FL-101, Placebo

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

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

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

FL-101 Monotherapy

Arm Type

Experimental

Arm Description

30 patients will receive FL-101 prior to surgery.

Arm Title

FL-101 + Nivolumab

Arm Type

Experimental

Arm Description

30 patients will receive FL-101 and Nivolumab prior to surgery.

Arm Title

Nivolumab + Placebo

Arm Type

Active Comparator

Arm Description

30 patients will receive Nivolumab and placebo prior to surgery.

Intervention Type

Drug

Intervention Name(s)

FL-101

Intervention Description

200 mg administered intravenously every 2 weeks prior to surgery.

Intervention Type

Drug

Intervention Name(s)

Nivolumab

Intervention Description

240 mg administered intravenously every 2 weeks prior to surgery.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

200 mg administered intravenously every 2 weeks prior to surgery.

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

From time of first dose to 3 months after surgery

Secondary Outcome Measure Information:

Title

Number of patients with treatment efficacy as assessed by pathological response (percentage of residual tumor) by independent pathology review.

Description

Time Frame

At time of surgery (around 6-8 weeks)

Title

Major Pathologic Response

Description

To determine major pathologic response (MPR), defined as ≤10 percent viable tumor

Time Frame

At time of surgery (around 6-8 weeks after first dose)

Title

Complete Pathologic Response

Description

To estimate complete pathologic response (CPR), defined as the absence of residual invasive cancer in resected lung specimens and lymph nodes

Time Frame

At time of surgery (around 6-8 weeks after first dose)

Title

Objective Response Rate (ORR)

Description

To estimate objective response rate (ORR) by RECIST 1.1

Time Frame

At time of surgery (around 6-8 weeks after first dose)

Title

MRD measurement by ctDNA

Description

To describe the time course of minimal residual disease (MRD) response by ctDNA and recurrence in correlation with clinical response

Time Frame

From time of first dose to 3 months after surgery

Other Pre-specified Outcome Measures:

Title

Plasma Concentration of FL-101

Description

To evaluate the pharmacokinetics of FL-101 in patients with NSCLC

Time Frame

From time of first dose up to 3 months after surgery

Title

Plasma IL-1β/IL-6 levels

Description

To evaluate the effect of FL-101 on pharmacodynamic biomarkers

Time Frame

From time of first dose up to 3 months after surgery

Title

Serum hsCRP

Description

To evaluate the effect of FL-101 on pharmacodynamic biomarkers

Time Frame

From enrollment up to 3 months after surgery

Title

Prevalence and incidence of Anti-FL-101 antibodies

Description

To evaluate possible immunogenicity of FL-101

Time Frame

From time of first dose up to 3 months after surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Cassandra Choe-Juliak, MD

Organizational Affiliation

Flame Biosciences

Official's Role

Study Director

12. IPD Sharing Statement

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

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