Description:
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). Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be
assessed.
Title
- Brief Title: FS118 First in Human Study in Patients With Advanced Malignancies
- Official Title: A Phase 1/2, Open-Label, First-in-Human Study to Evaluate the Safety and Anti-Tumor Activity of FS118, a LAG-3/PD-L1 Bispecific Antibody, in Patients With Advanced Malignancies
Clinical Trial IDs
- ORG STUDY ID:
FS118-17101
- NCT ID:
NCT03440437
Conditions
- Advanced Cancer
- Metastatic Cancer
- Squamous Cell Carcinoma of Head and Neck
Interventions
Drug | Synonyms | Arms |
---|
FS118 | | FS118 weekly |
Purpose
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). Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be
assessed.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | |
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Dose escalation: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) |
Time Frame: | 12 months |
Safety Issue: | |
Description: | Incidence, severity and duration of adverse events will be assessed by CTCAEv4.03 |
Secondary Outcome Measures
Measure: | Dose escalation: Disease Response as assessed by RECIST 1.1 and iRECIST |
Time Frame: | 7 months |
Safety Issue: | |
Description: | Assessed by RECIST 1.1 and iRECIST |
Measure: | Dose escalation: Incidence of FS118 immunogenicity |
Time Frame: | 7 months |
Safety Issue: | |
Description: | Incidence of FS118 immunogenicity will include ADA detection and analysis (incidence measured in titre) |
Measure: | Expansion cohort: Disease Response as assessed by RECIST 1.1 and iRECIST in all SCCHN participants |
Time Frame: | 24 weeks |
Safety Issue: | |
Description: | Assessed by RECIST 1.1 and iRECIST |
Measure: | Expansion cohort: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) |
Time Frame: | 12 months |
Safety Issue: | |
Description: | Incidence, severity and duration of adverse events will be assessed by CTCAEv4.03 |
Measure: | Expansion cohort: Maximum Serum Concentration of FS118 |
Time Frame: | 7 months |
Safety Issue: | |
Description: | Blood samples for serum PK analysis will be obtained (Cmax measured in mcg/mL) |
Measure: | Expansion cohort: Time to reach maximum serum concentration (Tmax) of FS118 |
Time Frame: | 7 months |
Safety Issue: | |
Description: | Blood samples for serum PK analysis will be obtained (Tmax measured in hours) |
Measure: | Expansion cohort: Trough serum concentration (Ctrough) of FS118 prior to the next dose |
Time Frame: | 7 months |
Safety Issue: | |
Description: | Blood samples for serum PK analysis will be obtained (Ctrough measured in mcg/mL) |
Measure: | Expansion cohort: Area under the serum FS118 concentration vs time Curve (AUC) |
Time Frame: | 7 months |
Safety Issue: | |
Description: | Blood samples for serum PK analysis will be obtained (AUC measured in d.mcg/mL) |
Measure: | Expansion cohort: Systemic Clearance (CL) of FS118 |
Time Frame: | 7 months |
Safety Issue: | |
Description: | Blood samples for serum PK analysis will be obtained (CL measured in mL/day) |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | F-star Therapeutics Limited |
Trial Keywords
- FS118
- Immuno-oncology
- bispecific antibody
- check-point inhibitor
- dose escalation
- cohort expansion
- PK
- PD
- biomarker
- LAG-3
- PD-L1
- SCCHN
- F-star
Last Updated
August 24, 2021