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

Metastatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03440437
• Other study ID #: FS118-17101
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 16, 2018
• Est. completion date: June 2024

Study information

• Verified date: July 2023
• Source: invoX Pharma Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 95
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Cancer
• Metastatic Cancer
• Squamous Cell Carcinoma of Head and Neck

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	CHU Bordeaux	Bordeaux
France	Centre Oscar Lambret	Lille
France	Centre Lyon Berard	Lyon
France	La Timone	Marseille
France	Centre Antoine Lacassagne	Nice
United States	Emory Healthcare	Atlanta	Georgia
United States	University of Cincinnati	Cincinnati	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of California Los Angeles (UCLA)	Los Angeles	California
United States	Yale University School of Medicine	New Haven	Connecticut
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
invoX Pharma Limited

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Dose escalation: Maximum Serum Concentration of FS118	Blood samples for serum PK analysis will be obtained (Cmax measured in mcg/mL)	7 months
Primary	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
Primary	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
Primary	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
Primary	Dose escalation: Systemic Clearance (CL) of FS118	Blood samples for serum PK analysis will be obtained (CL measured in mL/day)	7 months
Primary	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
Primary	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	Dose escalation: Disease Response as assessed by RECIST 1.1 and iRECIST	Assessed by RECIST 1.1 and iRECIST	7 months
Secondary	Dose escalation and expansion cohort of FS118 + paclitaxel	Incidence of FS118 immunogenicity will include ADA detection and analysis (incidence measured in titre)	7 months
Secondary	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
Secondary	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
Secondary	Expansion cohort: Maximum Serum Concentration of FS118	Blood samples for serum PK analysis will be obtained (Cmax measured in mcg/mL)	7 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Expansion cohort: Systemic Clearance (CL) of FS118	Blood samples for serum PK analysis will be obtained (CL measured in mL/day)	7 months