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

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

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer; Advanced Solid Tumors; Transitional Cell Carcinoma of the Bladder
• Intervention / Treatment: Drug: FPA144

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.

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seongnam-si, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University
  • Seoul, Korea, Republic of, 135-720
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of, 156-707
    • SMG-SNU Boramae Medical Center
  • Seoul, Korea, Republic of, 136-705
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 137-701
    • Seoul St. Mary's Hospital
  • Jeollabuk-do
    • Jeonju, Jeollabuk-do, Korea, Republic of, 561-712
      • Chonbuk National University Hospital
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center
    • San Francisco, California, United States, 74158
      • UCSF Helen Diller Family Comprehensive Cancer Center, Mission Bay
    • Whittier, California, United States, 90603
      • Innovative Cancer Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute, LLC
  • Texas
    • Houston, Texas, United States, 77030-4009
      • The University of Texas M.D. Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A: FPA144 Dose Escalation Solid Tumors; Dose escalation of FPA144 (0.3 mg/kg to 15 mg/kg)	Drug: FPA144; FPA144 will be administered by IV infusion over approximately 30 minutes every 2 weeks.; Other Names: Bemarituzumab
Experimental: Part 1B: FPA144 Dose Escalation Gastric Cancer; Dose escalation of FPA144 (3-10 mg/kg) in patients with gastric cancer	Drug: FPA144; FPA144 will be administered by IV infusion over approximately 30 minutes every 2 weeks.; Other Names: Bemarituzumab
Experimental: Part 2: FPA144 Dose Expansion Gastric or Other Solid Tumors; Evaluation of objective responses in patients with tumors with various levels of FGFR2b overexpression	Drug: FPA144; FPA144 will be administered by IV infusion over approximately 30 minutes every 2 weeks.; Other Names: Bemarituzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Five Prime Therapeutics, Inc.
• Investigators: Study Director: Medical Lead, Five Prime Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): February 28, 2019
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: November 25, 2014
• First Submitted That Met QC Criteria: December 12, 2014
• First Posted (Estimate): December 17, 2014

Study Record Updates

• Last Update Posted (Actual): December 13, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: FGFR2b, FGFR2, FGFR, bladder neoplasms, esophageal cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Bemarituzumab
• Other Study ID Numbers: FPA144-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data will be provided to investigative sites requesting information for secondary publication.
• IPD Sharing Time Frame: After publication of the primary endpoint results.
• IPD Sharing Access Criteria: Participating investigators in good standing.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL