FS222 First in Human Study in Patients With Advanced Malignancies

A Phase 1, Open-Label, First-in-Human Study to Evaluate the Safety and Anti-tumour Activity of FS222, a CD137/PD-L1 Bispecific Antibody, in Subjects With Advanced Malignancies

This study will be conducted in adult participants diagnosed with advanced tumours to characterize the safety, tolerability, pharmacokinetics (PK), and activity of FS222. 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 FS222 in participants with advanced tumours. Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Cancer; Advanced Cancer
• Intervention / Treatment: Drug: FS222

• Study Type: Interventional
• Enrollment (Estimated): 177
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: invoX Clinical Trials; Phone Number: +44 2038 820886; Email: info@invoxpharma.com

Study Locations

• Romania
  • Bucharest, Romania, 022322
    • Recruiting
    • Prof. Dr. Alexandru Trestioreanu Oncologic Institute
    • Contact: Laurentia Nicoleta Gales, MD
  • Bucharest, Romania, 10731
    • Recruiting
    • "Dr. Carol Davila" Nephrology Clinical Hospital
    • Contact: Alexandru Grigorescu, MD
  • Cluj-Napoca, Romania, 400015
    • Recruiting
    • Prof Dr I Chiricuta Institute of Oncology
    • Contact: Tudor Ciuleanu, MD
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Contact: Elena Garralda Cabanas, Ldo.
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínic de Barcelona
    • Contact: Javier Garcia Corbacho, Ldo.
  • Barcelona, Spain, 08023
    • Recruiting
    • NEXT - Hospital Quironsalud Barcelona
    • Contact: Guzman Alonso Casal, MD
  • Barcelona, Spain, 08916
    • Recruiting
    • Institut Catala d'Oncologia de Badalona
    • Contact: Marc Cucurull Salamero
  • Las Palmas De Gran Canaria, Spain, 35016
    • Recruiting
    • Complejo hospitalario Universitario Insular-Materno Infantil
    • Contact: Delvys Rodriguez-Abreu, MD
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
    • Contact: Gillermo de Velasco Oria de Rueda, Ldo.
  • Madrid, Spain, 28040
    • Recruiting
    • Instituto de Investigación Sanitaria Fundación Jimenez Díaz
    • Contact: Victor Moreno, MD
  • Madrid, Spain, 28050
    • Recruiting
    • NEXT - Hospital Universitario Quironsalud Madrid
    • Contact: Valentina Boni, MD
  • Majadahonda, Spain, 28222
    • Recruiting
    • Hospital Universitario Puerta de Hierro - Majadahonda
    • Contact: Mariano Provencio Pulla, MD
  • Seville, Spain, 41007
    • Recruiting
    • Universitary Hospital Virgen Macarena
    • Contact: Teresa Garcia Manrique, MD
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clínico Universitario de Valencia
    • Contact: Andrés Cervantes Ruiperez, Ldo.
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Clinica Universidad Navarra
      • Contact: Ignacio Melero Bermejo, Ldo.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years.
• Participants with histologically or cytologically confirmed, locally advanced, unresectable or metastatic solid tumours for whom standard therapy has proven to be ineffective, intolerable or is considered inappropriate. This criterion does not apply to the PK/PD expansion cohort, where tumour-specific criteria will apply instead.
• No more than 1 line of prior therapy with ICB treatment. Exceptions as defined in protocol for PK/PD expansion cohorts will apply.
• Participants who have received prior ICB, or any concurrent chemotherapy, radiotherapy, investigational, biologic or hormonal therapy for cancer treatment may be eligible for enrolment following a washout period.
• Participants who have received prior anti-PD-L1 therapy are eligible if PD-L1 therapy was discontinued ≥6 months prior to entry into the study.
• Participants who have failed a prior ICB regimen should document it.
• Measurable disease. Exceptions as defined in protocol for PK/PD expansion cohorts will apply.
• Eastern Cooperative Oncology Group Performance Status ≤1.
• The participant agrees to undergo a mandatory pre-treatment and on-treatment biopsy of the tumour. Certain exceptions apply.
• Highly effective contraception.
• Willing and able to provide written informed consent.

Exclusion Criteria:

• Participants with clinically relevant COVID-19 disease risk will be excluded from enrolment during the COVID-19 pandemic.
• Concurrent enrolment in another clinical study with the exception of non-interventional/observational studies or the follow-up period of an interventional study.
• Prior treatment with CD137 agonist mAb or other experimental agonists.
• For participants who have received prior ICB, participants must not have received more than 1 line of prior treatment with ICB(s). Exceptions as defined in protocol for PK/PD expansion cohorts will apply.
• Participants with active autoimmune disease.
• Receipt of any live virus vaccine within 30 days prior to the first dose of study drug.
• Receipt of a live attenuated vaccine within 30 days prior to the first dose of study drug.
• History of uncontrolled intercurrent illness.
• Psychological, familial, sociological or geographical conditions that do not permit compliance with the protocol.
• Judgment by the investigator that the participant is unsuitable to participate in the study, and the participant is unlikely to comply with study procedures, restrictions and requirements.
• Significant laboratory abnormalities.
• Known infections.
• Uncontrolled CNS metastases, primary CNS tumours with CNS metastases as only measurable disease. Exceptions as defined in protocol for PK/PD expansion cohorts will apply.
• Prior history of any Grade ≥3 irAE that has not improved to Grade ≤1, except for endocrine deficiencies that are managed by HRT; significant treatment-related cytokine release syndrome; systemic inflammatory response syndrome.
• Current use of immunosuppressive agents, prior organ transplantation requiring immunosuppression, hypersensitivity or intolerance to mAb or their excipients, or persisting toxicity related to prior therapy of Grade >1 NCI CTCAE Version 5.0 .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: FS222 Q4W; 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. Additional participants will be recruited into the PK/PD expansion cohorts at dose levels deemed safe during dose escalation. Once a tolerated dose has been established participants will be recruited into tumour-specific expansion cohorts.

Drug: FS222; Dosing of participants will occur intravenously (IV), at a fixed dose in treatment cycles once every 4 weeks (Q4W) until disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of adverse events (AEs) and serious adverse events (SAEs)	Safety and tolerability will be evaluated by collection of AEs and SAEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.	15 months
Determination of a maximum tolerated dose (MTD) by evaluation of DLTs	Toxicity will be evaluated according to the NCI CTCAE Version 5.0.	28 days
Determination of a recommended Phase 2 dose (RP2D) by evaluation of DLTs	Toxicity will be evaluated according to the NCI CTCAE Version 5.0.	28 days

Collaborators and Investigators

• Sponsor: invoX Pharma Limited

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2020
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: January 28, 2021
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (Actual): February 5, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Immunotherapy; PD-L1; Immuno-oncology; bispecific antibody; dose escalation; CD137; 4-1BB; cohort expansion; F-star
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: FS222-19101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No