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

Non-Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04758949
• Other study ID #: FL-101-2001
• Status: Withdrawn
• Phase: Phase 2
• Start date: August 25, 2021
• Est. completion date: December 22, 2021

Study information

• Verified date: December 2021
• Source: Flame Biosciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 22, 2021
• Est. primary completion date: December 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• FL-101
200 mg administered intravenously every 2 weeks prior to surgery.
• Nivolumab
240 mg administered intravenously every 2 weeks prior to surgery.
• Placebo
200 mg administered intravenously every 2 weeks prior to surgery.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Flame Biosciences

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Plasma IL-1ß/IL-6 levels	To evaluate the effect of FL-101 on pharmacodynamic biomarkers	From time of first dose up to 3 months after surgery
Other	Serum hsCRP	To evaluate the effect of FL-101 on pharmacodynamic biomarkers	From enrollment up to 3 months after surgery
Other	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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