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FS118 First in Human Study in Patients With Advanced Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03440437
Recruitment Status : Recruiting
First Posted : February 22, 2018
Last Update Posted : March 4, 2022
Sponsor:
Information provided by (Responsible Party):
F-star Therapeutics Limited

Tracking Information
First Submitted Date  ICMJE February 8, 2018
First Posted Date  ICMJE February 22, 2018
Last Update Posted Date March 4, 2022
Actual Study Start Date  ICMJE April 16, 2018
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2021)
  • 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
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: February 14, 2018)
  • Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) [ Time Frame: 12 months ]
    Incidence, severity and duration of treatment emergent adverse events will be assessed by CTCAEv4.03
  • 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)
  • Maximum Serum Concentration of FS118 [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (Cmax measured in mcg/mL)
  • 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)
  • 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)
  • 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)
  • Systemic Clearance (CL) of FS118 [ Time Frame: 7 months ]
    Blood samples for serum PK analysis will be obtained (CL measured in mL/day)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2021)
  • Dose escalation: Disease Response as assessed by RECIST 1.1 and iRECIST [ Time Frame: 7 months ]
    Assessed by RECIST 1.1 and iRECIST
  • Dose escalation: Incidence of FS118 immunogenicity [ Time Frame: 7 months ]
    Incidence of FS118 immunogenicity will include ADA detection and analysis (incidence measured in titre)
  • 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
  • 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
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2018)
  • Disease Response as assessed by RECIST 1.1 or the Lugano classification, as applicable, and iRECIST [ Time Frame: 7 months ]
    Assessed by RECIST 1.1 or the Lugano classification, as applicable, and iRECIST
  • Incidence of FS118 immunogenicity [ Time Frame: 7 months ]
    Incidence of FS118 immunogenicity will include ADA detection and analysis (incidence measured in titre)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE FS118 First in Human Study in Patients With Advanced Malignancies
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Cancer
  • Metastatic Cancer
  • Squamous Cell Carcinoma of Head and Neck
Intervention  ICMJE 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.
Study Arms  ICMJE 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.
Intervention: Drug: FS118
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 20, 2021)
80
Original Estimated Enrollment  ICMJE
 (submitted: February 14, 2018)
51
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: F-star Clinical Trials +1 617 798 1467 cambridge@f-star.com
Contact: F-star Clinical Trials +44 1223 497400
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03440437
Other Study ID Numbers  ICMJE FS118-17101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party F-star Therapeutics Limited
Original Responsible Party Same as current
Current Study Sponsor  ICMJE F-star Therapeutics Limited
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account F-star Therapeutics Limited
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP