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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Non Small Cell Lung Cancer; Advanced Urothelial Carcinoma
• Intervention / Treatment: Drug: Pembrolizumab; Drug: FF-10832

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 Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Cancer and Blood Speciality Clinic
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital (Oncology Clinical Research)
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center - Westwood
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Brown Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine, Center for Adv Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialists - Legacy
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Comprehensive Cancer Centers of Nevada - Southern Hills
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System / Morristown Medical Center
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10016
      • NYU Langone Health
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • TriHealth Cancer Institute; Good Samaritan Hospital
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute Franz Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the Univ of Pennsylvania Perlman Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Clinical Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run-in Phase; 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; Treatment at 200 mg pembrolizumab, administered intravenously (IV) on Day 1 of each 21-day cycle prior to infusion of FF-10832; Other Names: MK-3475; KEYTRUDA®; Drug: FF-10832; Following administration of pembrolizumab, FF-10832 Gemcitabine Liposome Injection, 40 mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle; Other Names: Gemcitabine Liposome Injection
Experimental: Urothelial Monotherapy - FF-10832 Expansion Phase; FF-10832 will be dosed at 40 mg/m2	Drug: FF-10832; Following administration of pembrolizumab, FF-10832 Gemcitabine Liposome Injection, 40 mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle; Other Names: Gemcitabine Liposome Injection
Experimental: Urothelial Combination - FF-10832 + pembrolizumab Expansion Phase; 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; Treatment at 200 mg pembrolizumab, administered intravenously (IV) on Day 1 of each 21-day cycle prior to infusion of FF-10832; Other Names: MK-3475; KEYTRUDA®; Drug: FF-10832; Following administration of pembrolizumab, FF-10832 Gemcitabine Liposome Injection, 40 mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle; Other Names: Gemcitabine Liposome Injection
Experimental: NSCLC Monotherapy - FF-10832 Expansion Phase; FF-10832 will be dosed at 40 mg/m2	Drug: FF-10832; Following administration of pembrolizumab, FF-10832 Gemcitabine Liposome Injection, 40 mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle; Other Names: Gemcitabine Liposome Injection
Experimental: NSCLC Combination - FF-10832 + pembrolizumab Expansion Phase; 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; Treatment at 200 mg pembrolizumab, administered intravenously (IV) on Day 1 of each 21-day cycle prior to infusion of FF-10832; Other Names: MK-3475; KEYTRUDA®; Drug: FF-10832; Following administration of pembrolizumab, FF-10832 Gemcitabine Liposome Injection, 40 mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle; Other Names: Gemcitabine Liposome Injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: March 29, 2022
• First Submitted That Met QC Criteria: April 7, 2022
• First Posted (Actual): April 8, 2022

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; pembrolizumab
• Other Study ID Numbers: FF10832-PEM-201/KEYNOTE-B57; MK-3475-B57 (Other Identifier: Merck Sharp & Dohme Corp)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No