Title
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

Description
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).

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.

Objective
Primary Objectives:
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.
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).
To obtain a preliminary estimate of efficacy of the combination in expansion cohorts of patients with UC and NSCLC.

Secondary Objectives:
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;
To describe the safety profile of the combination, including dose limiting toxicities, immune-related toxicities, and other treatment emergent AEs;
For each expansion cohort, determine the overall response rate (ORR), duration of response (DOR), evaluate progression-free survival (PFS), and overall survival (OS) for both FF-10832 monotherapy and combination therapy.

Treatment Drug: Pembrolizumab
Drug: FF-10832

Key Eligibility Inclusion Criteria:

Written informed consent is provided by patient or legally acceptable representative;

Age >/= 18 years;

Patient populations:



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 therapy

In Expansion Phase, patient must have urothelial or NSCLC, and have failed prior anti-PD-1 or anti-PD-L1



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

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.

Applicable Disease Sites
Bladder; Lung

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital