Clinical trial NCT05318573: A Study to Evaluate Safety, Efficacy of FF-10832 in Combo With Pembrolizumab in Urothelial & Non-small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Urothelial Carcinoma
Advanced Non Small Cell Lung Cancer
Lead sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-04-08
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Determine the incidence of Treament Emergent Adverse Events (TEAE)
timeFrame: 7 years
measure: Duration of Stable Disease in Monotherapy
timeFrame: 7 years
measure: Duration of Stable Disease in Combination Therapy
timeFrame: 7 years
Secondary outcomes:
measure: Determine Safety Profile of Monotherapy
timeFrame: 7 years
measure: Determine Safety Profile of Combination Therapy
timeFrame: 7 years
measure: Overall Response Rate (ORR)
timeFrame: 7 years
measure: Duration of Response (DOR)
timeFrame: 7 years
measure: Progression-free survival (PFS)
timeFrame: 7 years
measure: Overall survival (OS)
timeFrame: 7 years
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Cancer and Blood Speciality Clinic
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital (Oncology Clinical Research)
state: California
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Westwood
country: United States
facility: University of Kansas Cancer Center - Westwood
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Brown Cancer Center
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Center for Adv Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists - Legacy
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Southern Hills
state: Nevada
city: Morristown
country: United States
facility: Atlantic Health System / Morristown Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cincinnati
country: United States
facility: TriHealth Cancer Institute; Good Samaritan Hospital
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Institute Franz Clinic
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the Univ of Pennsylvania Perlman Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Clinical Science Center
state: Wisconsin
Study officials:
References: