Clinical trial NCT03440437: A Phase 1/2 Study of FS118 in Patients With Advanced Malignancies
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: invoX Pharma Limited
Sponsor class: INDUSTRY
First posted: 2018-02-22
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose escalation: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)
timeFrame: 12 months
measure: Dose escalation: Serum Concentration vs time profile of FS118
timeFrame: 7 months
measure: Dose escalation: Maximum Serum Concentration of FS118
timeFrame: 7 months
measure: Dose escalation: Time to reach maximum serum concentration (Tmax) of FS118
timeFrame: 7 months
measure: Dose escalation: Trough serum concentration (Ctrough) of FS118 prior to the next dose
timeFrame: 7 months
measure: Dose escalation: Area under the serum FS118 concentration vs time Curve (AUC)
timeFrame: 7 months
measure: Dose escalation: Systemic Clearance (CL) of FS118
timeFrame: 7 months
measure: Expansion cohort: Disease control rate as assessed by RECIST 1.1 in evaluable participants with PD-L1 and LAG-3 positive SCCHN
timeFrame: 24 weeks
measure: Expansion cohort (FS118 + paclitaxel): Incidence of Treatment Emergent Adverse Events (safety and Tolerability) Incidence, severity and duration of adverse events
timeFrame: 12 months
Secondary outcomes:
measure: Dose escalation: Disease Response as assessed by RECIST 1.1 and iRECIST
timeFrame: 7 months
measure: Dose escalation and expansion cohort of FS118 + paclitaxel
timeFrame: 7 months
measure: Expansion cohort: Disease Response as assessed by RECIST 1.1 and iRECIST in all SCCHN participants
timeFrame: 24 months
measure: Expansion cohort: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)
timeFrame: 12 months
measure: Expansion cohort: Maximum Serum Concentration of FS118
timeFrame: 7 months
measure: Expansion cohort: Time to reach maximum serum concentration (Tmax) of FS118
timeFrame: 7 months
measure: Expansion cohort: Trough serum concentration (Ctrough) of FS118 prior to the next dose
timeFrame: 7 months
measure: Expansion cohort: Area under the serum FS118 concentration vs time Curve (AUC)
timeFrame: 7 months
measure: Expansion cohort: Systemic Clearance (CL) of FS118
timeFrame: 7 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Atlanta
country: United States
facility: Emory Healthcare
state: Georgia
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Lyon Berard
city: Marseille
country: France
facility: La Timone
city: Nice
country: France
facility: Centre Antoine Lacassagne
Study officials:
References: