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FS118 First in Human Study in Patients With Advanced Malignancies After PD-1/PD-L1 Containing Therapy

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ClinicalTrials.gov Identifier: NCT03440437
Recruitment Status : Recruiting
First Posted : February 21, 2018
Last Update Posted : January 29, 2019
Sponsor:
Information provided by (Responsible Party):
F-star Delta Limited

Brief Summary:
This study will be conducted in adult patients diagnosed with advanced tumors to characterize the safety, tolerability, pharmacokinetics (PK), and activity of FS118. This is a Phase 1, multi-center, open label, multiple-dose, first in human study, designed to systematically assess safety and tolerability, and to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) for FS118 in patients with advanced tumors. Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.

Condition or disease Intervention/treatment Phase
Advanced Cancer Metastatic Cancer Drug: FS118 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 51 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Dose-Escalation, and Cohort Expansion First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Activity of FS118, a LAG-3/PD-L1 Bispecific Antibody, in Patients With Advanced Malignancies That Have Progressed On or After Prior PD-1/PD-L1 Containing Therapy
Actual Study Start Date : April 16, 2018
Estimated Primary Completion Date : December 16, 2019
Estimated Study Completion Date : May 16, 2020

Arm Intervention/treatment
Experimental: FS118 weekly
The initial cohorts will enroll sequentially as single-patient cohorts. If no DLT or ≥Grade 2 study drug related adverse event is observed, then dosing will proceed in a 3+3 design.
Drug: FS118
Dosing of patients will occur intravenously (IV) weekly in 3-week treatment cycles until iCPD (ie, immune confirmed progressive disease) (or progressive disease [PD] per the Lugano classification for patients with lymphoma), unacceptable toxicity, or discontinuation.




Primary Outcome Measures :
  1. 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

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

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


Secondary Outcome Measures :
  1. 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

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



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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:

  • Age ≥18 years;
  • Patients with histologically confirmed, locally advanced, unresectable, or metastatic solid tumors or hematological malignancies 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.

Exclusion Criteria:

  • 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;
  • Patients 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 patient's participation in the study, as per the Investigator's judgment.

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: Melinda Snyder 617-233-4057 FS118@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: Maria Casado    310-794-6913      
Principal Investigator: Deborah Wong, MD, PhD         
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Contact: Caroline Hotchkiss    203-737-5228    caroline.hotchkiss@yale.edu   
Principal Investigator: Patricia LoRusso, DO         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sandra Montez    713-745-6274    smontez@mdanderson.org   
Principal Investigator: Timothy A Yap, MD, PhD         
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
Contact: Lauryn Tuckett    210-593-5242    Lauryn.Tuckett@startsa.com   
Principal Investigator: Kyri Papadopoulos, MD         
Sponsors and Collaborators
F-star Delta Limited
Investigators
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Study Director: Josefin-Beate Holz, MD

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Responsible Party: F-star Delta Limited
ClinicalTrials.gov Identifier: NCT03440437     History of Changes
Other Study ID Numbers: FS118-17101
First Posted: February 21, 2018    Key Record Dates
Last Update Posted: January 29, 2019
Last Verified: January 2019
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

Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs