Open-Label, Dose-Finding Study Evaluating Safety and PK of FPA144 in Patients With Advanced Solid Tumors

Gastric Cancer Clinical Trial

Official title:

A Phase 1 Open-Label, Dose-Finding Study Evaluating Safety and Pharmacokinetics of FPA144 in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02318329
• Other study ID #: FPA144-001
• Status: Completed
• Phase: Phase 1
• Start date: November 2014
• Est. completion date: June 30, 2019

Study information

• Verified date: December 2021
• Source: Five Prime Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: June 30, 2019
• Est. primary completion date: February 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Carcinoma, Transitional Cell
• Gastric Cancer
• Transitional Cell Carcinoma of the Bladder
• Urinary Bladder Neoplasms

Intervention

Drug:
• FPA144
FPA144 will be administered by IV infusion over approximately 30 minutes every 2 weeks.

Locations

Country	Name	City	State
Korea, Republic of	Chonbuk National University Hospital	Jeonju	Jeollabuk-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center	Seoul
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	The University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	Sarah Cannon Research Institute, LLC	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Weill Cornell Medical Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	UCSF Helen Diller Family Comprehensive Cancer Center, Mission Bay	San Francisco	California
United States	Innovative Cancer Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Five Prime Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Taiwan, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Protocol Specified Dose-limiting Toxicities (Part 1 Only).	Number of participants with grade 3 and grade 4 adverse events (AE) and clinical laboratory abnormalities defined as dose limiting toxicities (DLTs)	4 weeks on average
Primary	Number of Participants With AEs and Clinical Laboratory Abnormalities (Parts 1B and 2 Only)	Number of Participants with AEs and clinical laboratory abnormalities (Parts 1B and 2 only)	16 weeks on average
Secondary	Pharmacokinetic (PK) Profile of FPA144: Maximum Serum Concentration	Sampling following the first dose in Part 1, pre and post-dose at selected cycles, and at the end of treatment for both Part 1 and Part 2.; • Summary of area under serum concentration-time curve, maximum serum concentration,	16 weeks on average
Secondary	Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	16 weeks on average
Secondary	Duration of Response Per RECIST 1.1 (Part 2 Only)	Duration of complete or partial response with 95% confidence intervals in gastric cancer population.	16 weeks on average
Secondary	Pharmacokinetic (PK) Profile of FPA144: Area Under Serum Concentration-time Curve	Sampling following the first dose in Part 1, pre and post-dose at selected cycles, and at the end of treatment for both Part 1 and Part 2.; • Summary of area under serum concentration-time curve, maximum serum concentration,	16 weeks on average