A Study to Evaluate Safety, Efficacy of FF-10832 in Combination With Pembrolizumab in Solid Tumors

Study Overview
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Brief Summary
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To confirm a recommended Phase 2 dose (RP2D) of FF-10832 (Gemcitabine Liposome Injection) given intravenously Day 1 of a 21-day cycle, in combination with 200 mg pembrolizumab given intravenously Day 1 of the same 21-day cycle, for treatment of advanced solid tumors.

Detailed Description
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This is a Phase 2a, open label clinical trial evaluating FF-10832 in combination with pembrolizumab and as monotherapy. The trial will begin with a safety run-in phase of 10 patients receiving combination therapy with pembrolizumab; FF 10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg). The dose of FF-10832 may be reduced to 30 mg/m2 and tested in 10 patients after review of safety data by a safety review committee (SRC). Lower or intermediate doses of FF-10832 may be explored if necessary After confirmation of the appropriate FF-10832 dose for use with pembrolizumab, the trial will enroll up to an additional 100 patients in 2 cohorts (urothelial cancer [UC] and non-small cell lung cancer [NSCLC]) into 4 separate expansion treatment arms (approximately 25 patients in each treatment arm). The disease-defined cohorts will be patients who have progressed on PD-1/PD-L1 therapy who have UC or NSCLC. The UC cohort will be randomized (1:1) to one of two treatment arms (monotherapy or combination therapy) and the NSCLC cohort will be randomized (1:1) to one of two treatment arms (monotherapy or combination therapy), to further establish safety and gain preliminary information on antitumor activity of FF-10832 as monotherapy or in combination with pembrolizumab.

Official Title
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A Phase 2a Study With Safety Run-in to Evaluate the Safety, Tolerability, and Preliminary Efficacy of FF-10832 Monotherapy or in Combination With Pembrolizumab in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: FF-10832


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent is provided by patient or legally acceptable representative; Age ≥ 18 years; Patient populations: a. In the Safety Run-in, patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have disease progression after treatment with standard therapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment or refuse standard treatment will be enrolled in this study Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology Eastern Cooperative Oncology Group performance status of 0 to 1 Life expectancy of ≥ 3 months Exclusion Criteria: Positive urine pregnancy test within 72 hours prior to treatment. I Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (or 5 half-lives, whichever is shorter) prior to treatment; Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), AND was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event; Has received prior radiotherapy within 2 weeks of start of study treatment. For patients with NSCLC: Patients who have received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of trial treatment are excluded; Patients with mutations (e.g., EGFR mutations or ALK gene rearrangements) will be excluded unless they have been previously treated with all specific targeted therapies. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Has had an allogeneic tissue /solid organ transplant.

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
Interventional Model Description: FF-10832 (Gemcitabine Liposome Injection) given intravenously Day 1 of a 21-day cycle, in combination with 200 mg pembrolizumab given intravenously Day 1 of the same 21-day cycle
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safety Run-in Phase<br>FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg) | Drug: Pembrolizumab<br>* Treatment at 200 mg pembrolizumab, administered intravenously (IV) on Day 1 of each 21-day cycle prior to infusion of FF-10832<br>* Other names: MK-3475;Drug: FF-10832<br>* Following administration of pembrolizumab, FF-10832 Gemcitabine Liposome Injection, 40 mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle<br>* Other names: Gemcitabine Liposome Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the incidence of Treament Emergent Adverse Events (TEAE) | Safety and tolerability assessed by adverse events (AEs) and serious adverse events (SAEs) and to confirm dose (RP2D) of FF-10832 given intravenously Day 1 of a 21 day cycle, in combination with 200 mg pembrolizumab, given intravenously Day 1 of the same 21-day cycle, for treatment of advanced solid tumors. | 7 years | 
| Duration of Stable Disease in Monotherapy | To obtain a preliminary estimate of efficacy of FF-10832 monotherapy in expansion cohorts of patients with urothelial cancer (UC) and non-small cell lung cancer (NSCLC). Duration of Stable Disease is the length of time from the start of the treatment until the criteria for progression are met | 7 years | 
| Duration of Stable Disease in Combination Therapy | To obtain a preliminary estimate of efficacy of the combination in expansion cohorts of patients with UC and NSCLC. Duration of Stable Disease is the length of time from the start of the treatment until the criteria for progression | 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Safety Profile of Monotherapy | To describe the safety profile of FF-10832 monotherapy 40 mg/m2 given intravenously Day 1 of a 21-day cycle, including treatment-emergent AEs. Safety assessed by adverse events (AEs) and serious adverse events (SAEs) | 7 years | 
| Determine Safety Profile of Combination Therapy | Describe the safety profile of the combination, including dose limiting toxicities, immune related toxicities, and other treatment emergent AEs. Safety assessed by adverse events (AEs) and serious adverse events (SAEs) | 7 years | 
| Overall Response Rate (ORR) | Overall Response Rate is determined by classification of solid tumors via RECIST v.1.1 | 7 years | 
| Duration of Response (DOR) | Duration of Response is calculated from the date of first response to the date of progression or death | 7 years | 
| Progression-free survival (PFS) | Progression-free survival will be calculated from the date of first treatment to the date of progression or death | 7 years | 
| Overall survival (OS) | Overall survival will be calculated from the date of first treatment to the date of death from any cause | 7 years |