A Phase 1/2 Study of FS118 in Patients With Advanced Malignancies

A Phase 1/2, Open-Label, Study to Evaluate the Safety and Anti-Tumor Activity of FS118, a LAG-3/PD-L1 Bispecific Antibody, as a Monotherapy and in Combination With Paclitaxel, in Patients With Advanced Malignancies

This study will be conducted in adult participants diagnosed with advanced tumors to characterize the safety, tolerability, pharmacokinetics (PK), and activity of FS118. This is a Phase 1/2, multi-center, open-label, multiple-dose, first-in-human study, designed to systematically assess safety and tolerability, to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) for FS118 in participants with advanced tumors and to determine the efficacy of FS118 in participants with squamous cell carcinoma of the head and neck (SCCHN) as monotherapy and in combination with paclitaxel. In addition to safety, pharmacokinetics, pharmacodynamics, immunogenicity and efficacy will also be assessed.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Cancer; Squamous Cell Carcinoma of Head and Neck; Advanced Cancer
• Intervention / Treatment: Drug: FS118; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: F-star Clinical Trials; Phone Number: +1 617 798 1467; Email: cambridge@f-star.com
• Study Contact Backup: Name: F-star Clinical Trials; Phone Number: +44 1223 497400

Study Locations

• France
  • Bordeaux, France
    • CHU Bordeaux
  • Lille, France
    • Centre Oscar Lambret
  • Lyon, France
    • Centre Lyon Berard
  • Marseille, France
    • La Timone
  • Nice, France
    • Centre Antoine Lacassagne
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles (UCLA)
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Healthcare
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All participants:

• Age ≥18 years;
• Participants with histologically confirmed, locally advanced, unresectable, or metastatic solid tumors that progressed while on or after PD-1/PD-L1 containing therapy;
• Measurable disease;
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1;
• Life expectancy estimated to be at least 3 months;
• Highly effective contraception;
• Willing and able to provide written informed consent.

Expansion cohort only:

• Histologically and/or cytologically confirmed recurrent/metastatic (R/M) SCCHN that is not amenable to curative therapy by surgery or radiation;
• Only 1 prior anti-PD-1 or anti-PD-L1 therapy and documented PD-L1 scoring ≥1% by combined positive score or tumor proportion score as part of their treatment;
• An anti-PD-1 or anti-PD-L1 treatment regimen must be the last prior therapy before study enrollment, following no more than 2 prior systemic regimens for R/M SCCHN;
• Acquired resistance to an anti-PD-1- or anti-PD-L1-containing therapy;
• The participant agrees to undergo a pre-treatment and on-treatment core or excisional biopsy and the biopsy procedure is not judged to be high risk by the Investigator.

Exclusion Criteria:

All participants:

• Participant is deemed at high risk of fatal outcome in case of COVID-19;
• Participants with a history of COVID-19 and have not provided a negative test for SARS CoV-2 infection within 28 days of the planned first dose date with FS118;
• Prior therapy: Received systemic anti-cancer therapy within 28 days or 5 half-lives, of the first dose of study drug, or prior treatment with a LAG-3 inhibitor;
• Participants with active or documented history of autoimmune disease;
• History of uncontrolled intercurrent illness;
• Known infections;
• Uncontrolled CNS metastases, primary CNS tumors, or solid tumors with CNS metastases as only measurable disease;
• Prior history of or active interstitial lung disease or pneumonitis, encephalitis, seizures, severe immune related adverse events with prior PD-1/PD-L1 containing treatments;
• Significant cardiac abnormalities;
• Significant laboratory abnormalities;
• Intolerance to the investigational product or its excipients, or any condition that would significantly impair and/or prohibit the participants's participation in the study, as per the Investigator's judgment.

Expansion cohort only:

• Participant has nasopharynx or thyroid primary tumor site;
• History of severe immune-related toxicity during the prior treatment with checkpoint inhibitors.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FS118 weekly; The initial cohorts will enroll sequentially as single-participant cohorts. If no DLT or ≥Grade 2 study drug related adverse event is observed, then dosing will proceed in a 3+3 design followed by an expansion cohort of participants with SCCHN and an expansion SCCHN cohort in combination with Paclitaxel.	Drug: FS118; Dosing of participants will occur intravenously (IV) weekly in 3-week treatment cycles until iCPD (i.e., immune confirmed progressive disease), unacceptable toxicity, or discontinuation.; Drug: Paclitaxel; Dosing on Days 1, 8 and 15 of each 28 day cycle in combination with FS118 given on days 1, 8, 15 and 22 of each 28 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose escalation: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)	Incidence, severity and duration of adverse events will be assessed by CTCAEv4.03	12 months
Dose escalation: Serum Concentration vs time profile of FS118	Blood samples for serum PK analysis will be obtained (concentrations measured in mcg/mL)	7 months
Dose escalation: Maximum Serum Concentration of FS118	Blood samples for serum PK analysis will be obtained (Cmax measured in mcg/mL)	7 months
Dose escalation: Time to reach maximum serum concentration (Tmax) of FS118	Blood samples for serum PK analysis will be obtained (Tmax measured in hours)	7 months
Dose escalation: Trough serum concentration (Ctrough) of FS118 prior to the next dose	Blood samples for serum PK analysis will be obtained (Ctrough measured in mcg/mL)	7 months
Dose escalation: Area under the serum FS118 concentration vs time Curve (AUC)	Blood samples for serum PK analysis will be obtained (AUC measured in d.mcg/mL)	7 months
Dose escalation: Systemic Clearance (CL) of FS118	Blood samples for serum PK analysis will be obtained (CL measured in mL/day)	7 months
Expansion cohort: Disease control rate as assessed by RECIST 1.1 in evaluable participants with PD-L1 and LAG-3 positive SCCHN	Assessed by RECIST 1.1	24 weeks
Expansion cohort (FS118 + paclitaxel): Incidence of Treatment Emergent Adverse Events (safety and Tolerability) Incidence, severity and duration of adverse events	Assessed by CTCAE v 5.0	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose escalation: Disease Response as assessed by RECIST 1.1 and iRECIST	Assessed by RECIST 1.1 and iRECIST	7 months
Expansion cohort: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)	Incidence, severity and duration of adverse events will be assessed by CTCAEv4.03	12 months
Expansion cohort: Maximum Serum Concentration of FS118	Blood samples for serum PK analysis will be obtained (Cmax measured in mcg/mL)	7 months
Expansion cohort: Time to reach maximum serum concentration (Tmax) of FS118	Blood samples for serum PK analysis will be obtained (Tmax measured in hours)	7 months
Expansion cohort: Trough serum concentration (Ctrough) of FS118 prior to the next dose	Blood samples for serum PK analysis will be obtained (Ctrough measured in mcg/mL)	7 months
Expansion cohort: Area under the serum FS118 concentration vs time Curve (AUC)	Blood samples for serum PK analysis will be obtained (AUC measured in d.mcg/mL)	7 months
Expansion cohort: Systemic Clearance (CL) of FS118	Blood samples for serum PK analysis will be obtained (CL measured in mL/day)	7 months
Expansion cohort: Disease Response as assessed by RECIST 1.1 and iRECIST in all SCCHN participants	Assessed by RECIST 1.1 and iRECIST	24 months
Dose escalation and expansion cohort of FS118 + paclitaxel	Incidence of FS118 immunogenicity will include ADA detection and analysis (incidence measured in titre)	7 months

Collaborators and Investigators

• Sponsor: invoX Pharma Limited

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2018
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: February 8, 2018
• First Submitted That Met QC Criteria: February 14, 2018
• First Posted (Actual): February 22, 2018

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: biomarker; PK; PD-L1; LAG-3; Immuno-oncology; PD; bispecific antibody; dose escalation; SCCHN; cohort expansion; F-star; FS118; check-point inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: FS118-17101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No