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

NCT03440437 | Terminated Phase 1 FDA Drug

• 1 other identifier: FS118-17101
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 12

Brief 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.

Conditions

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

Keywords

FS118; Immuno-oncology; bispecific antibody; check-point inhibitor; dose escalation; cohort expansion; PK; PD; biomarker; LAG-3; PD-L1; SCCHN; F-star

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (9)

• Dose escalation: Disease Response as assessed by RECIST 1.1 and iRECIST

  7 months

• Dose escalation and expansion cohort of FS118 + paclitaxel

  7 months

• Expansion cohort: Disease Response as assessed by RECIST 1.1 and iRECIST in all SCCHN participants

  24 months

• Expansion cohort: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)

  12 months

• Expansion cohort: Maximum Serum Concentration of FS118

  7 months

Study Arms (1)

FS118 weekly

EXPERIMENTAL

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; Drug: Paclitaxel

Interventions

FS118 DRUG

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.

FS118 weekly

Paclitaxel DRUG

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.

FS118 weekly

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• invoX Pharma Limited: lead

Study Sites (12)

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Emory Healthcare

Atlanta, Georgia, 30322, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

CHU Bordeaux

Bordeaux, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Lyon Berard

Lyon, France

Location

La Timone

Marseille, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Related Publications (1)

• Yap TA, LoRusso PM, Wong DJ, Hu-Lieskovan S, Papadopoulos KP, Holz JB, Grabowska U, Gradinaru C, Leung KM, Marshall S, Reader CS, Russell R, Sainson RCA, Seal CJ, Shepherd CJ, Germaschewski F, Gliddon D, Stern O, Young L, Brewis N, Kayitalire L, Morrow M. A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance. Clin Cancer Res. 2023 Mar 1;29(5):888-898. doi: 10.1158/1078-0432.CCR-22-1449.

  PMID: 36342102 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Squamous Cell Carcinoma of Head and Neck

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2018
• First Posted: February 22, 2018
• Study Start: April 16, 2018
• Primary Completion: June 21, 2024
• Study Completion: June 21, 2024
• Last Updated: July 1, 2025

Record last verified: 2024-07

Locations

FR (5); US (7)