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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05181865
Recruitment Status : Not yet recruiting
First Posted : January 6, 2022
Last Update Posted : January 6, 2022
Sponsor:
Information provided by (Responsible Party):
Flame Biosciences

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Phase 1 Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 115 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a, First-In-Human, Open Label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of FL-301 in Patients With Advanced Solid Tumors
Estimated Study Start Date : February 2022
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : February 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1 - Cohort 1 Drug: 1 mg/kg IV FL-301
N = 1
Other Name: FL-301

Experimental: Phase 1 - Cohort 2 Drug: 3 mg/kg IV FL-301
N = 3-6
Other Name: FL-301

Experimental: Phase 1 - Cohort 3 Drug: 10 mg/kg IV FL-301
N = 3-6
Other Name: FL-301

Experimental: Phase 1 - Cohort 4 Drug: 20 mg/kg IV FL-301
N = 3-6
Other Name: FL-301

Experimental: Phase 1 - Cohort 5 Drug: 30 mg/kg IV FL-301
N = 3-6
Other Name: FL-301

Experimental: Phase 2a - Group 1 Drug: RP2D, IV FL-301
Pancreatic Cancer N = 30
Other Name: FL-301

Experimental: Phase 2a - Group 2 Drug: RP2D, IV FL-301
Gastric Cancer (Including GEJ) N = 30
Other Name: FL-301

Experimental: Phase 2a - Group 3 Drug: RP2D, IV FL-301
Other Solid Tumors N = 30
Other Name: FL-301




Primary Outcome Measures :
  1. Phase 1: The incidence of DLTs (during DLT observation period) [ Time Frame: Up to 12 months ]
    Determine the MTD, and/or to select an RP2D, and investigate the safety and tolerability of FL-301 in patients with advanced solid malignancies

  2. Phase 2a (Expansion): ORR (CR + PR) assessed centrally by RECIST v1.1 [ Time Frame: Up to 12 months ]
    Assess the preliminary antitumor efficacy of FL-301, by central RECIST v1.1


Secondary Outcome Measures :
  1. Phase 1: Incidence of patients with TEAEs and SAEs [ Time Frame: Up to 12 months ]
    Characterize the safety and tolerability of FL-301

  2. Phase 1: Incidence of patients who develop ADAs and neutralizing ADAs during treatment with FL-301 [ Time Frame: Up to 12 months ]
    Characterize the immunogenicity of FL-301

  3. Phase 1: ORR (CR + PR), DOR, and DCR assessed locally by RECIST v1.1 [ Time Frame: Up to 12 months ]
    Assess the preliminary antitumor efficacy of FL-301

  4. Phase 1: PK parameters - Cmax [ Time Frame: Up to 12 months ]
    Characterize the PK of FL-301

  5. Phase 1: PK parameters - Tmax [ Time Frame: Up to 12 months ]
    Characterize the PK of FL-301

  6. Phase 1: PK parameters - AUC (0-∞) [ Time Frame: Up to 12 months ]
    Characterize the PK of FL-301

  7. Phase 1: PK parameters - AUC (0-τ) [ Time Frame: Up to 12 months ]
    Characterize the PK of FL-301

  8. Phase 1: PK parameters - Half-life (t1/2) [ Time Frame: Up to 12 months ]
    Characterize the PK of FL-301


Other Outcome Measures:
  1. Phase 1 (Exploratory): ORR (CR + PR), DOR, and DCR assessed centrally by RECIST v1.1 [ Time Frame: Up to 12 months ]
    Assess the preliminary antitumor efficacy of FL-301

  2. Phase 1 (Exploratory): Explore the predictive potential of biomarkers measured in blood and/or tumor tissue in response to FL-301 [ Time Frame: Up to 12 months ]
    Explore the predictive potential of biomarkers measured in blood and/or tumor tissue in response to FL-301



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

General Inclusion Criteria

Applicable to all patients in both the Phase 1 and Phase 2a parts of the study:

  • 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.

Specific criteria for Phase 1:

  • 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.

Specific criteria for Phase 2a:

  • 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

Exclusion Criteria

Patients who meet any of the following criteria will be excluded:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05181865


Contacts
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Contact: Head of Clinical Operations 1-833-50-FLAME (35263) clinicaltrials@flame.bio

Sponsors and Collaborators
Flame Biosciences
Investigators
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Study Director: Cassandra Choe-Juliak, MD Flame Biosciences
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Responsible Party: Flame Biosciences
ClinicalTrials.gov Identifier: NCT05181865    
Other Study ID Numbers: FL-301-1001
First Posted: January 6, 2022    Key Record Dates
Last Update Posted: January 6, 2022
Last Verified: January 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Flame Biosciences:
FL-301
Pancreatic Cancer
Gastric Cancer
GEJ
Gastroesophageal Cancer
Solid Tumor
Claudin 18.2
Additional relevant MeSH terms:
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Stomach Neoplasms
Pancreatic Neoplasms
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases