A Study to Evaluate Safety, Efficacy of FF-10832 in Combo With Pembrolizumab in Urothelial & Non-small Cell Lung Cancer

Phase 2

Recruiting

• Conditions: Advanced Non Small Cell Lung Cancer; Advanced Urothelial Carcinoma
• Interventions: Drug: FF-10832; Drug: Pembrolizumab

• Registration Number: NCT05318573
• Lead Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.

Brief Summary

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 urothelial and non-small cell lung cancer

Detailed 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.

Study Timeline

• Study First Submitted: 2022-03-29
• Study First Submitted QC: 2022-04-07
• Study First Posted: 2022-04-08
• Study Start: 2022-06-01
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-09
• Last Update Posted: 2025-04-10
• Primary Completion: 2029-05
• Study Completion: 2029-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

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

2. Age ≥ 18 years;

3. Patient populations:

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

4. Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology

5. Eastern Cooperative Oncology Group performance status of 0 to 1

6. Life expectancy of ≥ 3 months

Exclusion Criteria

1. Positive urine pregnancy test within 72 hours prior to treatment

2. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (or 5 half-lives, whichever is shorter) prior to treatment;

3. 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;

4. Has received prior radiotherapy within 2 weeks of start of study treatment.

5. For patients with NSCLC:

   1. 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;
   2. 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.

6. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.

7. Has had an allogeneic tissue /solid organ transplant.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Urothelial Monotherapy - FF-10832 Expansion Phase	FF-10832	FF-10832 will be dosed at 40 mg/m2
Urothelial Combination - FF-10832 + pembrolizumab Expansion Phase	FF-10832	FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)
NSCLC Monotherapy - FF-10832 Expansion Phase	FF-10832	FF-10832 will be dosed at 40 mg/m2
Safety Run-in Phase	FF-10832	FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)
NSCLC Combination - FF-10832 + pembrolizumab Expansion Phase	FF-10832	FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)
Safety Run-in Phase	Pembrolizumab	FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)
Urothelial Combination - FF-10832 + pembrolizumab Expansion Phase	Pembrolizumab	FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)
NSCLC Combination - FF-10832 + pembrolizumab Expansion Phase	Pembrolizumab	FF-10832 in combination therapy with pembrolizumab; FF-10832 will be dosed at 40 mg/m2 with a fixed dose of pembrolizumab (200 mg)

Primary Outcome Measures

Name	Time	Method
Duration of Stable Disease in Combination Therapy	7 years	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
Determine the incidence of Treament Emergent Adverse Events (TEAE)	7 years	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.
Duration of Stable Disease in Monotherapy	7 years	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

Secondary Outcome Measures

Name	Time	Method
Determine Safety Profile of Combination Therapy	7 years	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)
Overall Response Rate (ORR)	7 years	Overall Response Rate is determined by classification of solid tumors via RECIST v.1.1
Progression-free survival (PFS)	7 years	Progression-free survival will be calculated from the date of first treatment to the date of progression or death
Overall survival (OS)	7 years	Overall survival will be calculated from the date of first treatment to the date of death from any cause
Determine Safety Profile of Monotherapy	7 years	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)
Duration of Response (DOR)	7 years	Duration of Response is calculated from the date of first response to the date of progression or death

Trial Locations

Locations (23)

Cancer and Blood Speciality Clinic; 🇺🇸 Long Beach, California, United States

Sharp Memorial Hospital (Oncology Clinical Research); 🇺🇸 San Diego, California, United States

Nebraska Cancer Specialists - Legacy; 🇺🇸 Omaha, Nebraska, United States

Sibley Memorial Hospital; 🇺🇸 Washington, District of Columbia, United States

University of Kansas Cancer Center - Westwood; 🇺🇸 Westwood, Kansas, United States

Washington University School of Medicine, Center for Adv Medicine; 🇺🇸 Saint Louis, Missouri, United States

NYU Langone Health; 🇺🇸 New York, New York, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

University of Kentucky Medical Center; 🇺🇸 Lexington, Kentucky, United States

University of Louisville Brown Cancer Center; 🇺🇸 Louisville, Kentucky, United States

Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion); 🇺🇸 Detroit, Michigan, United States

Comprehensive Cancer Centers of Nevada - Southern Hills; 🇺🇸 Las Vegas, Nevada, United States

Providence Cancer Institute Franz Clinic; 🇺🇸 Portland, Oregon, United States

Hospital of the Univ of Pennsylvania Perlman Center; 🇺🇸 Philadelphia, Pennsylvania, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Atlantic Health System / Morristown Medical Center; 🇺🇸 Morristown, New Jersey, United States

TriHealth Cancer Institute; Good Samaritan Hospital; 🇺🇸 Cincinnati, Ohio, United States

Avera Cancer Institute; 🇺🇸 Sioux Falls, South Dakota, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Virginia Cancer Specialists, PC; 🇺🇸 Fairfax, Virginia, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

University of Wisconsin Clinical Science Center; 🇺🇸 Madison, Wisconsin, United States