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

Phase 1

Withdrawn

• Conditions: Gastric Cancer; Solid Tumor; Pancreas Cancer
• Interventions: Drug: RP2D, IV FL-301; Drug: 3 mg/kg IV FL-301; Drug: 20 mg/kg IV FL-301; Drug: 10 mg/kg IV FL-301; Drug: 1 mg/kg IV FL-301; Drug: 30 mg/kg IV FL-301

• Registration Number: NCT05181865
• Lead Sponsor: 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.

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.

Study Timeline

• Study First Submitted: 2021-12-17
• Status Verified: 2022-01
• Study Start: 2022-01
• Study First Submitted QC: 2022-01-05
• Study First Posted: 2022-01-06
• Primary Completion: 2022-01-18
• Study Completion: 2022-01-18
• Last Update Submitted: 2022-01-31
• Last Update Posted: 2022-02-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 2a - Group 2	RP2D, IV FL-301	-
Phase 1 - Cohort 2	3 mg/kg IV FL-301	-
Phase 1 - Cohort 4	20 mg/kg IV FL-301	-
Phase 1 - Cohort 3	10 mg/kg IV FL-301	-
Phase 2a - Group 1	RP2D, IV FL-301	-
Phase 1 - Cohort 1	1 mg/kg IV FL-301	-
Phase 2a - Group 3	RP2D, IV FL-301	-
Phase 1 - Cohort 5	30 mg/kg IV FL-301	-

Primary Outcome Measures

Name	Time	Method
Phase 2a (Expansion): ORR (CR + PR) assessed centrally by RECIST v1.1	Up to 12 months	Assess the preliminary antitumor efficacy of FL-301, by central RECIST v1.1
Phase 1: The incidence of DLTs (during DLT observation period)	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

Secondary Outcome Measures

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