Phase 1/2a Study To Evaluate FL-301 In Patients With Advanced Solid Tumors

Study Overview

Phase 1/2a Study to Evaluate FL-301 in Patients With Advanced Solid Tumors

This is a Phase 1/2a, first-in-human, open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of FL-301 in patients with advanced cancer.

This is a Phase 1/2a, first-in-human, open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of FL-301 in patients with advanced cancer. The study will consist of 2 phases, Phase 1 and Phase 2a. In Phase 1, dose escalation will proceed according to a rule-based design methodology. Phase 1 will explore dosing in which a single dose of FL-301 is administered by intravenous (IV) infusion every 2 weeks (Q2W) in 4-week cycles. Patients with measurable advanced solid tumors expressing claudin 18.2 may be enrolled, with the cutoff levels further defined in the eligibility criteria. Dose escalation methodology (modified 3+3 design) will utilize prespecified dose increments. Once the RP2D has been established, Phase 2a will commence to explore preliminary evidence of antitumor efficacy and confirm the safety of FL-301. The dosing schedule will be explored in up to 3 separate patient groups of approximately 30 patients per group. Group 1 will include patients with pancreatic cancer; Group 2 will include patients with gastric cancer (including gastroesophageal junction [GEJ]); and Group 3 will include patients with any other solid tumor (primarily non-small cell lung cancer [NSCLC], ovarian, and cholangiocarcinoma with claudin 18.2 expression). Response and progression will be evaluated in this study using computerized tomography (CT) or magnetic resonance imaging (MRI) imaging per RECIST v1.1. Long-term follow-up (survival and disease status, as applicable) will be conducted up to 18 months or until death, start of new anticancer therapy, end of study, or withdrawal of consent, whichever occurs first.

Pancreas Cancer
Gastric Cancer
Solid Tumor

DRUG: 1 mg/kg IV FL-301
DRUG: 3 mg/kg IV FL-301
DRUG: 10 mg/kg IV FL-301
DRUG: 20 mg/kg IV FL-301
DRUG: 30 mg/kg IV FL-301
DRUG: RP2D, IV FL-301
DRUG: RP2D, IV FL-301
DRUG: RP2D, IV FL-301

FL-301-1001

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-12-17	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2022-01-31
First Submitted that Met QC Criteria 2022-01-05	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2022-02-07
First Posted (ACTUAL) 2022-01-06	Results First Posted N/A	Last Verified 2022-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase 1 - Cohort 1	DRUG: 1 mg/kg IV FL-301 N = 1
EXPERIMENTAL: Phase 1 - Cohort 2	DRUG: 3 mg/kg IV FL-301 N = 3-6
EXPERIMENTAL: Phase 1 - Cohort 3	DRUG: 10 mg/kg IV FL-301 N = 3-6
EXPERIMENTAL: Phase 1 - Cohort 4	DRUG: 20 mg/kg IV FL-301 N = 3-6
EXPERIMENTAL: Phase 1 - Cohort 5	DRUG: 30 mg/kg IV FL-301 N = 3-6
EXPERIMENTAL: Phase 2a - Group 1	DRUG: RP2D, IV FL-301 Pancreatic Cancer N = 30
EXPERIMENTAL: Phase 2a - Group 2	DRUG: RP2D, IV FL-301 Gastric Cancer (Including GEJ) N = 30
EXPERIMENTAL: Phase 2a - Group 3	DRUG: RP2D, IV FL-301 Other Solid Tumors N = 30

Primary Outcome Measures	Measure Description	Time Frame
Phase 1: The incidence of DLTs (during DLT observation period)	Determine the MTD, and/or to select an RP2D, and investigate the safety and tolerability of FL-301 in patients with advanced solid malignancies	Up to 12 months
Phase 2a (Expansion): ORR (CR + PR) assessed centrally by RECIST v1.1	Assess the preliminary antitumor efficacy of FL-301, by central RECIST v1.1	Up to 12 months

Secondary Outcome Measures	Measure Description	Time Frame
Phase 1: Incidence of patients with TEAEs and SAEs	Characterize the safety and tolerability of FL-301	Up to 12 months
Phase 1: Incidence of patients who develop ADAs and neutralizing ADAs during treatment with FL-301	Characterize the immunogenicity of FL-301	Up to 12 months
Phase 1: ORR (CR + PR), DOR, and DCR assessed locally by RECIST v1.1	Assess the preliminary antitumor efficacy of FL-301	Up to 12 months
Phase 1: PK parameters - Cmax	Characterize the PK of FL-301	Up to 12 months
Phase 1: PK parameters - Tmax	Characterize the PK of FL-301	Up to 12 months
Phase 1: PK parameters - AUC (0-∞)	Characterize the PK of FL-301	Up to 12 months
Phase 1: PK parameters - AUC (0-τ)	Characterize the PK of FL-301	Up to 12 months
Phase 1: PK parameters - Half-life (t1/2)	Characterize the PK of FL-301	Up to 12 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histological or cytologically confirmed locally advanced or metastatic solid tumor
Life expectancy >12 weeks.
Age ≥18 years.
ECOG performance status 0 or 1 at screening.
Fully vaccinated against COVID-19 at least 3 weeks before C1D1. If under consideration for a booster, the booster administration needs to be complete within the same time constraint (ie, at least 3 weeks before C1D1).
Adequate organ function, defined as:

Hematology: defined as absolute neutrophil count (ANC) ≥1.5×109/L, platelet ≥90×109/L, hemoglobin ≥9.0 g/dL (in the absence of transfusion and use of growth factors within the last 14 days of screening labs).
Renal function defined as calculated creatinine clearance (CCr) or radioisotope glomerular filtration rate >60 mL/min/1.73 m2 calculated by Cockcroft-Gault formula or normal serum creatinine with a maximum serum creatinine of 1.5 mg/dL.
Hepatic Function:

Alanine aminotransferase (ALT) ≤2.5 × ULN; ≤5 × ULN if with liver metastases.
Total bilirubin ≤1.5×ULN.
Serum Electrolytes:

Serum potassium, calcium, magnesium, and phosphate within normal limits or not worse than CTCAE v5.0 Grade 1 and asymptomatic. If values are low on the initial screening assessment, supplements may be given, if clinically appropriate, and values repeated to confirm within CTCAE v5.0 Grade 1 limits.

Positive claudin 18.2 tumor expression defined as ≥50% of tumor cells demonstrating moderate-to-strong membranous staining (2+/3+) by IHC assay performed on sections of tumor derived from formalin fixed paraffin block.
Pathological diagnosis (histological) of any solid tumor cancer with positive claudin 18.2 tumor expression as defined above.

Positive claudin 18.2 tumor expression defined as ≥70% of tumor cells demonstrating moderate-to-strong membranous staining (2+/3+) by IHC assay performed on sections of tumor derived from formalin fixed paraffin block.
At least 1 measurable target lesion as defined by RECIST 1.1
Disease progression or relapse following conventional chemotherapy, patient must have documented radiological progression during or after their most recent anticancer therapy:

Pancreatic cancer: Patient should have received at least one but no more than two systemic therapies for their metastatic diseases
Gastric cancer (including GEJ cancer): Patient should have received at least two but no more than three systemic therapies for their metastatic diseases;
Other solid tumor cancers: Patients with other solid tumors who have no standard therapies available

History of severe infusion reaction with monoclonal antibody treatment.
Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening.
Known history of HIV.
Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
Presence of other active cancers, or history of treatment for invasive cancer ≤3 years. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (ie, noninvasive) are eligible, as are patients with history of nonmelanoma skin cancer.
Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
Active central nervous system (CNS) disease involvement, defined by cerebrospinal fluid (CSF) cytology, magnetic resonance imaging (MRI) or computerized tomography (CT); patients with asymptomatic CNS metastases are eligible if they have been clinically stable for at least 4 weeks prior to the first dose of study drug and do not require interventions such as surgery, radiation or any corticosteroid therapy for management of symptoms related to CNS disease.
Pregnant or nursing (lactating) women (Appendix B).
Patients who received claudin 18.2 targeting agents previously.
Prior radiotherapy:

Non-CNS site of radiation must be completed >2 weeks prior to FL-301 infusion
CNS directed radiation must be completed >4 weeks prior to FL-301 infusion as long as patients are asymptomatic post radiation therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Cassandra Choe-Juliak, MD, Flame Biosciences

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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