Clinical trial NCT02318329: Open-Label, Dose-Finding Study Evaluating Safety and PK of FPA144 in Patients With Advanced Solid Tumors
Official title: A Phase 1 Open-Label, Dose-Finding Study Evaluating Safety and Pharmacokinetics of FPA144 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Gastric Cancer
Transitional Cell Carcinoma of the Bladder
Keywords: FGFR2b, FGFR2, FGFR, bladder neoplasms, esophageal cancer
Lead sponsor: Five Prime Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2014-12-17
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a three-part, open-label, safety, tolerability, and PK study of FPA144. Patients will be enrolled in Part 1 (A or B, dose escalation) or Part 2 (dose expansion) of the study, but not both.

Detailed description: Part 1A is a dose-escalation study in patients with any locally advanced or metastatic solid tumor or lymphoma for which standard therapies have been exhausted. Part 1B will further assess safety and evaluate PK of FPA144 in gastric cancer patients.

Part 2 patients will be enrolled and treated in order to further characterize safety and preliminary efficacy in a selected cancer patient population with the greatest potential for clinical benefit from FPA144 treatment.

Eligibility criteria: Inclusion Criteria:

* Life expectancy of at least 3 months
* ECOG performance status of 0 to 1

  • In sexually-active patients, willingness to use 2 effective methods of contraception
* Adequate hematological and organ function, confirmed by lab values
* Tumor tissue must be available for prospective determination of FGFR2b overexpression

  * Locally recurrent or metastatic disease that has progressed on or following standard treatment, or is not a candidate for standard treatment
  * Histologically or cytologically confirmed transitional cell carcinoma of the genitourinary tract
  * Measurable disease as defined by RECIST version 1.1

Exclusion Criteria:

* Untreated or symptomatic central nervous system (CNS) metastases
* Impaired cardiac function or clinically significant cardiac disease

  - Treatment with any anticancer therapy or participation in another therapeutic clinical study with investigational drugs \</=14 days (\</=28 days for patients in Korea) prior to first dose of FPA144
* Ongoing acute adverse effects from prior anticancer or investigational therapy \> NCI CTCAE Grade 1
* Retinal disease or a history of retinal disease or detachment
* Corneal defects, corneal ulcerations, keratitis, keratoconus, history of corneal transplant, or other known abnormalities of the cornea
* Major surgical procedures are not allowed ≤28 days prior to FPA144 administration
* Females who are pregnant or breastfeeding; women of childbearing potential must not be considering getting pregnant during the study

  - Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
* Known allergy or hypersensitivity to components of the FPA144 formulation including polysorbate
* History of prior malignancy except:
* a) Curatively treated non-melanoma skin cancer or
* b) Solid tumor treated curatively more than 5 years previously without evidence of recurrence or
* c) History of other malignancy that in the Investigator's opinion would not affect the determination of study treatment effect
* Prior treatment with any selective inhibitor (e.g., AZD4547, BGJ398, JNJ-42756493, BAY1179470) of the FGF-FGFR pathway

Primary outcomes:
measure: Number of Participants With Protocol Specified Dose-limiting Toxicities (Part 1 Only).
timeFrame: 4 weeks on average
measure: Number of Participants With AEs and Clinical Laboratory Abnormalities (Parts 1B and 2 Only)
timeFrame: 16 weeks on average
Secondary outcomes:
measure: Pharmacokinetic (PK) Profile of FPA144: Maximum Serum Concentration
timeFrame: 16 weeks on average
measure: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: 16 weeks on average
measure: Duration of Response Per RECIST 1.1 (Part 2 Only)
timeFrame: 16 weeks on average
measure: Pharmacokinetic (PK) Profile of FPA144: Area Under Serum Concentration-time Curve
timeFrame: 16 weeks on average
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center, Mission Bay
state: California
city: Whittier
country: United States
facility: Innovative Cancer Research Institute
state: California
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute, LLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Jeonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
state: Jeollabuk-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Five Prime Therapeutics, Inc.
name: Medical Lead
role: STUDY_DIRECTOR
References:
citation: Catenacci DV, Tesfaye A, Tejani M, Cheung E, Eisenberg P, Scott AJ, Eng C, Hnatyszyn J, Marina N, Powers J, Wainberg Z. Bemarituzumab with modified FOLFOX6 for advanced FGFR2-positive gastroesophageal cancer: FIGHT Phase III study design. Future Oncol. 2019 Jun;15(18):2073-2082. doi: 10.2217/fon-2019-0141. Epub 2019 May 16.
citation: Catenacci DVT, Rasco D, Lee J, Rha SY, Lee KW, Bang YJ, Bendell J, Enzinger P, Marina N, Xiang H, Deng W, Powers J, Wainberg ZA. Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients With Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma. J Clin Oncol. 2020 Jul 20;38(21):2418-2426. doi: 10.1200/JCO.19.01834. Epub 2020 Mar 13.
citation: Xiang H, Liu L, Gao Y, Ahene A, Macal M, Hsu AW, Dreiling L, Collins H. Population pharmacokinetic analysis of phase 1 bemarituzumab data to support phase 2 gastroesophageal adenocarcinoma FIGHT trial. Cancer Chemother Pharmacol. 2020 Nov;86(5):595-606. doi: 10.1007/s00280-020-04139-4. Epub 2020 Sep 23.