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

Advanced Solid Tumor Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05318573
• Other study ID #: FF10832-PEM-201/KEYNOTE-B57
• Secondary ID: MK-3475-B57
• Status: Recruiting
• Phase: Phase 2
• Start date: June 1, 2022
• Est. completion date: November 2029

Study information

• Verified date: May 2024
• Source: Fujifilm Pharmaceuticals U.S.A., Inc.
• Contact: FPHU Study Coordinator
• Email: fphucontact[@]fujifilm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: November 2029
• Est. primary completion date: May 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• Pembrolizumab
Treatment at 200 mg pembrolizumab, administered intravenously (IV) on Day 1 of each 21-day cycle prior to infusion of FF-10832
• 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

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina
United States	TriHealth Cancer Institute; Good Samaritan Hospital	Cincinnati	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)	Detroit	Michigan
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Comprehensive Cancer Centers of Nevada - Southern Hills	Las Vegas	Nevada
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	University of Louisville Brown Cancer Center	Louisville	Kentucky
United States	University of Wisconsin Clinical Science Center	Madison	Wisconsin
United States	Atlantic Health System / Morristown Medical Center	Morristown	New Jersey
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	NYU Langone Health	New York	New York
United States	Hospital of the Univ of Pennsylvania Perlman Center	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Providence Cancer Institute Franz Clinic	Portland	Oregon
United States	Washington University School of Medicine, Center for Adv Medicine	Saint Louis	Missouri
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	University of Kansas Cancer Center - Westwood	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Fujifilm Pharmaceuticals U.S.A., Inc.	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	Overall Response Rate (ORR)	Overall Response Rate is determined by classification of solid tumors via RECIST v.1.1	7 years
Secondary	Duration of Response (DOR)	Duration of Response is calculated from the date of first response to the date of progression or death	7 years
Secondary	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
Secondary	Overall survival (OS)	Overall survival will be calculated from the date of first treatment to the date of death from any cause	7 years