FS222 First in Human Study in Patients With Advanced Malignancies

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: FS222


Participation Criteria
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Eligibility Criteria
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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 .

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FS222 Q4W<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immuno-oncology, bispecific antibody, dose escalation, cohort expansion, CD137, PD-L1, F-star, 4-1BB, Immunotherapy