FS118 First in Human Study in Patients With Advanced Malignancies

• ClinicalTrials.gov Identifier: NCT03440437
• Recruitment Status: Recruiting
• First Posted: February 22, 2018
• Last Update Posted: March 4, 2022
• Sponsor: F-star Therapeutics Limited
• Information provided by (Responsible Party): F-star Therapeutics Limited

Tracking Information

• First Submitted Date: February 8, 2018
• First Posted Date: February 22, 2018
• Last Update Posted Date: March 4, 2022
• Actual Study Start Date: April 16, 2018
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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)

Current Secondary Outcome Measures (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 (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: 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
• 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Cancer
• Metastatic Cancer
• Squamous Cell Carcinoma of Head and Neck

Intervention

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

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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 20, 2021): 80
• Original Estimated Enrollment (submitted: February 14, 2018): 51
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: F-star Clinical Trials; +1 617 798 1467; cambridge@f-star.com

Contact: F-star Clinical Trials; +44 1223 497400

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03440437
• Other Study ID Numbers: 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

• Plan to Share IPD: Undecided

• Current Responsible Party: F-star Therapeutics Limited
• Original Responsible Party: Same as current
• Current Study Sponsor: F-star Therapeutics Limited
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: F-star Therapeutics Limited
• Verification Date: March 2022