FPT155 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study is a Phase 1 open-label, first-in-human, multicenter study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and activity of FPT155 as monotherapy in patients with advanced solid tumors.

Detailed Description
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This Phase 1 study is comprised of dose escalation and cohort expansions for FPT155 monotherapy and for FPT155 in combination with pembrolizumab. Monotherapy dose escalation is designed with initial accelerated titration followed by a standard 3+3 dose escalation; combination dose escalation uses a standard 3+3 design. Patients will remain on study treatment until progression of disease, unacceptable toxicity, or other specified reason for discontinuation.

Official Title
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A Phase 1 Safety and Tolerability Study of FPT155 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Biological: FPT155
* Biological: pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed solid tumors (except primary central nervous system tumors). For patients enrolled for treatment with FPT155+pembrolizumab: histologically confirmed non-small cell lung cancer not eligible for curative therapy. Disease that is unresectable, locally advanced, or metastatic and has progressed following all standard treatments or is not appropriate for standard treatments All patients must have at least one measurable lesion at baseline according to RECIST v1.1 Availability of archival tumor tissue and consent to provide archival tumor for retrospective biomarker analysis, or consent to undergo a fresh tumor biopsy during screening For patients participating in cohort expansions: consent to undergo a mandatory fresh tumor biopsy during screening and on treatment ECOG performance status of 0 or 1 Prior radiotherapy must be completed at least 2 weeks before first dose of study treatment administration. No radiopharmaceuticals (eg, strontium, samarium) within 8 weeks before first dose of study treatment administration. Prior surgery that requires general anesthesia must be completed at least 14 days before first dose of study treatment Adequate bone marrow, liver and kidney function Exclusion Criteria: Uncontrolled or significant cardiac disease Any uncontrolled medical condition or psychiatric disorder including infection, autoimmune disease, bleeding disorder or symptomatic involvement of the central nervous system Treatment with any anti-cancer therapy or participation in another investigational drug or biologics trial within 28 days or ≤ 5 half-lives (whichever is shorter) Patients who discontinue prior immune-modulating therapies (including regimens containing an immune agonist or a PD-L1/PD-1 antagonist) due to toxicity or have received treatment within 5 half lives or 90 days Pregnancy or breastfeeding For patients participating in cohort expansion: Prior treatment with a CTLA-4 antagonist, including ipilimumab and tremelimumab

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Two arm trial with multiple cohorts
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FPT155 monotherapy<br>The study consists of dose escalation and cohort expansions | Biological: FPT155<br>* A soluble CD80 fusion protein<br>|
| Experimental: FPT155 in combination with pembrolizumab<br>The study consists of dose escalation and cohort expansions | Biological: FPT155<br>* A soluble CD80 fusion protein<br>Biological: pembrolizumab<br>* An anti-PD1 antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monotherapy: Maximum tolerated dose (MTD) of FPT155 | Determined by the frequency of dose-limiting toxicities during dose-escalation | Approximately 16 months | 
| Monotherapy: Incidence of treatment emergent adverse events | Severity graded per CTCAE version 4.03 | Through study completion, approximately 30 months | 
| FPT155 + pembrolizumab: Maximum tolerated dose (MTD) of FPT155 | Determined by the frequency of dose-limiting toxicities during dose-escalation | Approximately 12 months | 
| FPT155 + pembrolizumab: Incidence of treatment emergent adverse events | Severity graded per CTCAE version 4.03 | Through study completion, approximately 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile FPT155 | Area under serum concentration-time curve of FPT155 | Through study completion, approximately 30 months | 
| Incidence of treatment emergent anti-FPT155 antibody response | Immunogenicity | Through study completion, approximately 30 months | 
| Pharmacokinetic profile FPT155 | Maximum serum concentration of FPT155 | Through study completion, approximately 30 months | 
| Pharmacokinetic profile FPT155 | Trough serum concentration of FPT155 | Through study completion, approximately 30 months | 
| Pharmacokinetic profile FPT155 | Clearance of FPT155 | Through study completion, approximately 30 months | 
| Pharmacokinetic profile FPT155 | Terminal Half-Life of FPT155 | Through study completion, approximately 30 months | 
| Pharmacokinetic profile FPT155 | Volume of distribution | Through study completion, approximately 30 months | 
| Objective response rate | Defined as the proportion of patients with a response of either complete response or partial response as determined by investigator per RECIST v1.1 | Through study treatment, approximately a median of 6 months | 
| Cohort Expansions only: Progression-free survival | Defined as the total duration from enrollment to disease progression or death | Approximately a median of 6 months | 
| Cohort Expansions only: Duration of response | Time from complete or partial response per RECIST v1.1, until progression of disease or death | Approximately a median of 9 months |