FS120 First in Human Study in Patients With Advanced Malignancies

Sponsor

F-star Therapeutics Limited (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04648202

Collaborator

Merck Sharp & Dohme LLC (Industry)

277

Enrollment

Locations

Arm

35.4

Anticipated Duration (Months)

34.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1, multicenter, open-label, multiple-dose, multi part, first in human study in adult subjects with specific advanced malignancies. The study is designed to systematically assess safety, and tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, clinical activity and to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) for FS120 as a monotherapy and in combination with pembrolizumab.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancer Metastatic Cancer	Drug: FS120	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

277 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Open-Label Study to Evaluate the Safety and Antitumor Activity of FS120, an OX40/CD137 Bispecific Antibody, Alone and in Combination With Pembrolizumab, in Subjects With Advanced Malignancies

Actual Study Start Date :

Nov 18, 2020

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FS120 Open-label study where FS120 will be administered as monotherapy or in combination with pembrolizumab in dose escalation and expansion cohorts	Drug: FS120 Dosing of participants with FS120 or the combination will occur intravenously (IV), at a fixed dose in treatment cycles once every 4 weeks (Q4W) or once every 3 weeks (Q3W) until confirmed progressive disease (CPD)/immune-confirmed progressive disease (iCPD) or unacceptable toxicity.

Arm

Intervention/Treatment

Experimental: FS120

Open-label study where FS120 will be administered as monotherapy or in combination with pembrolizumab in dose escalation and expansion cohorts

Drug: FS120

Dosing of participants with FS120 or the combination will occur intravenously (IV), at a fixed dose in treatment cycles once every 4 weeks (Q4W) or once every 3 weeks (Q3W) until confirmed progressive disease (CPD)/immune-confirmed progressive disease (iCPD) or unacceptable toxicity.

Outcome Measures

Primary Outcome Measures

Incidence, severity, and duration of adverse events (AEs), serious adverse events (SAEs) and dose limiting toxicities (DLTs) [15 months]
Safety and tolerability will be evaluated by collection of AEs, SAEs and DLTs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
Determination of a maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) by evaluation of DLTs [28 days]
Toxicity will be evaluated according to the NCI CTCAE Version 5.0.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years.
Measurable disease.
Eastern Cooperative Oncology Group Performance Status 0-1.
The participant agrees to undergo a pretreatment and on-treatment biopsy of the tumor.
Highly effective contraception.
A female participant is eligible if not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP) or is a WOCBP that uses highly effective contraception.
Participants with human immunodeficiency virus (HIV) who are healthy and have a low risk of acquired immunodeficiency syndrome related outcomes.
For monotherapy part: participants must have histologically confirmed, locally advanced, unresectable or metastatic solid tumors of specific types.
For combination part: participants must have histologically confirmed, locally advanced, unresectable or metastatic solid tumors where there is regulatory approval for use of pembrolizumab as a monotherapy agent.

Exclusion Criteria:

Prior systemic anticancer therapy within 28 days or 5 half-lives, whichever is shorter, before the first dose of study drug.
Prior therapy with any OX40 agonist, CD137 (4-1BB) agonist, CD40 agonist, GITR, or CD27 targeting therapy (single agent or combination).
Prior therapy with more than 1 line of treatment with immune-checkpoint inhibitors (including ICB combination therapy).
Prior radiotherapy within 2 weeks of start of study treatment.
HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
Uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis, primary CNS tumours, or solid tumours with CNS metastases as the only measurable disease.
Prior history of any grade ≥3 immune-related AE (irAE) that has not improved to grade ≤1; any grade ≥3 irAE that resulted in discontinuation of treatment; significant (grade ≥3 NCI CTCAE Version 5.0) treatment-related cytokine release syndrome; systemic inflammatory response syndrome.
Use of immunosuppressive agents, hypersensitivity or intolerance to monoclonal antibodies or their excipients, persistent grade >1 NCI CTCAE Version 5.0 toxicity related to prior therapy or any condition that would significantly impair and/or prohibit the participant's participation in the study, as per the investigator's judgment.
Vaccination with a live vaccine within 30 days before first dose of study drug.
Participants with a known additional malignancy that is progressing or has required active treatment in the past 3 years.
Participants with severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	New Haven	Connecticut	United States	06511
2	MD Anderson Cancer Center	Houston	Texas	United States	77030
3	South Texas Accelerated Research Therapeutics (START)	San Antonio	Texas	United States	78229
4	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah	United States	84112
5	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
6	Hospital Universitario Fundacion Jimenez Diaz	Madrid		Spain	28040
7	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
8	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010