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Trial record 1 of 1 for:    FS118-17101
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FS118 First in Human Study in Patients With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT03440437
Recruitment Status : Recruiting
First Posted : February 22, 2018
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
F-star Delta Limited

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). Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.

Condition or disease Intervention/treatment Phase
Advanced Cancer Metastatic Cancer Squamous Cell Carcinoma of Head and Neck Drug: FS118 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 16, 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


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.
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.




Primary Outcome Measures :
  1. Dose escalation: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) [ Time Frame: 12 months ]
    Incidence, severity and duration of adverse events will be assessed by CTCAEv4.03

  2. Dose escalation: Serum Concentration vs time profile of FS118 [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (concentrations measured in mcg/mL)

  3. Dose escalation: Maximum Serum Concentration of FS118 [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (Cmax measured in mcg/mL)

  4. Dose escalation: Time to reach maximum serum concentration (Tmax) of FS118 [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (Tmax measured in hours)

  5. Dose escalation: Trough serum concentration (Ctrough) of FS118 prior to the next dose [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (Ctrough measured in mcg/mL)

  6. Dose escalation: Area under the serum FS118 concentration vs time Curve (AUC) [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (AUC measured in d.mcg/mL)

  7. Dose escalation: Systemic Clearance (CL) of FS118 [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (CL measured in mL/day)

  8. Expansion cohort: Disease control rate as assessed by RECIST 1.1 in evaluable participants with PD-L1 and LAG-3 positive SCCHN [ Time Frame: 24 weeks ]
    Assessed by RECIST 1.1


Secondary Outcome Measures :
  1. Dose escalation: Disease Response as assessed by RECIST 1.1 and iRECIST [ Time Frame: 7 months ]
    Assessed by RECIST 1.1 and iRECIST

  2. Dose escalation: Incidence of FS118 immunogenicity [ Time Frame: 7 months ]
    Incidence of FS118 immunogenicity will include ADA detection and analysis (incidence measured in titre)

  3. Expansion cohort: Disease Response as assessed by RECIST 1.1 and iRECIST in all SCCHN participants [ Time Frame: 24 weeks ]
    Assessed by RECIST 1.1 and iRECIST

  4. Expansion cohort: Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) [ Time Frame: 12 months ]
    Incidence, severity and duration of adverse events will be assessed by CTCAEv4.03

  5. Expansion cohort: Maximum Serum Concentration of FS118 [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (Cmax measured in mcg/mL)

  6. Expansion cohort: Time to reach maximum serum concentration (Tmax) of FS118 [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (Tmax measured in hours)

  7. Expansion cohort: Trough serum concentration (Ctrough) of FS118 prior to the next dose [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (Ctrough measured in mcg/mL)

  8. Expansion cohort: Area under the serum FS118 concentration vs time Curve (AUC) [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (AUC measured in d.mcg/mL)

  9. Expansion cohort: Systemic Clearance (CL) of FS118 [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (CL measured in mL/day)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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;
  • 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;
  • No more than 2 prior systemic regimens for R/M SCCHN;
  • An anti-PD-1 or anti-PD-L1 treatment regimen must be the last prior therapy before study enrollment, and this should be ≥28 days but <12 weeks from last treatment discontinuation and first dose in this study;
  • Acquired resistance to an anti-PD-1- or anti-PD-L1-containing therapy;
  • Confirmed radiographic disease progression on prior anti-PD-1- or anti-PD-L1-containing regimen;
  • 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:

  • Participants with clinically relevant COVID-19 risk will be excluded from enrollment during the COVID-19 pandemic;
  • Prior treatment with more than 1 checkpoint inhibitor (combination); prior treatment with a lymphocyte-activation gene 3 (LAG-3) inhibitor; prior treatment with multi specific checkpoint inhibitor molecules;
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03440437


Contacts
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Contact: F-star Clinical Trials +44 1223 497400 cambridge@f-star.com

Locations
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United States, California
University of California Los Angeles (UCLA) Recruiting
Los Angeles, California, United States, 90095
Contact: Deborah Wong, MD, PhD         
United States, Connecticut
Yale University School of Medicine Active, not recruiting
New Haven, Connecticut, United States, 06520
United States, Texas
MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Timothy A Yap, MD, PhD         
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
Contact: Kyri Papadopoulos, MD         
Sponsors and Collaborators
F-star Delta Limited
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Responsible Party: F-star Delta Limited
ClinicalTrials.gov Identifier: NCT03440437    
Other Study ID Numbers: FS118-17101
First Posted: February 22, 2018    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by F-star Delta Limited:
FS118
Immuno-oncology
bispecific antibody
check-point inhibitor
dose escalation
cohort expansion
PK
PD
biomarker
LAG-3
PD-L1
SCCHN
F-star
Additional relevant MeSH terms:
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Squamous Cell Carcinoma of Head and Neck
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Head and Neck Neoplasms
Neoplasms by Site