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

Phase 1

Completed

• Conditions: Transitional Cell Carcinoma of the Bladder; Gastric Cancer; Advanced Solid Tumors
• Interventions: Drug: FPA144

• Registration Number: NCT02318329
• Lead Sponsor: Five Prime Therapeutics, Inc.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2014-11
• Study First Submitted: 2014-11-25
• Study First Submitted QC: 2014-12-12
• Study First Posted: 2014-12-17
• Primary Completion: 2019-02-28
• Study Completion: 2019-06-30
• Results First Submitted: 2019-07-18
• Results First Submitted QC: 2020-02-26
• Results First Posted: 2020-03-11
• Status Verified: 2021-12
• Last Update Submitted: 2024-05-10
• Last Update Posted: 2024-06-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1A: FPA144 Dose Escalation Solid Tumors	FPA144	Dose escalation of FPA144 (0.3 mg/kg to 15 mg/kg)
Part 1B: FPA144 Dose Escalation Gastric Cancer	FPA144	Dose escalation of FPA144 (3-10 mg/kg) in patients with gastric cancer
Part 2: FPA144 Dose Expansion Gastric or Other Solid Tumors	FPA144	Evaluation of objective responses in patients with tumors with various levels of FGFR2b overexpression

Primary Outcome Measures

Name	Time	Method
Number of Participants With Protocol Specified Dose-limiting Toxicities (Part 1 Only).	4 weeks on average	Number of participants with grade 3 and grade 4 adverse events (AE) and clinical laboratory abnormalities defined as dose limiting toxicities (DLTs)
Number of Participants With AEs and Clinical Laboratory Abnormalities (Parts 1B and 2 Only)	16 weeks on average	Number of Participants with AEs and clinical laboratory abnormalities (Parts 1B and 2 only)

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Profile of FPA144: Maximum Serum Concentration	16 weeks on average	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,
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	16 weeks on average	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.
Duration of Response Per RECIST 1.1 (Part 2 Only)	16 weeks on average	Duration of complete or partial response with 95% confidence intervals in gastric cancer population.
Pharmacokinetic (PK) Profile of FPA144: Area Under Serum Concentration-time Curve	16 weeks on average	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,

Trial Locations

Locations (26)

Ronald Reagan UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

The University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

UCSF Helen Diller Family Comprehensive Cancer Center, Mission Bay; 🇺🇸 San Francisco, California, United States

Sarah Cannon Research Institute, LLC; 🇺🇸 Nashville, Tennessee, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

SMG-SNU Boramae Medical Center; 🇰🇷 Seoul, Korea, Republic of

China Medical University Hospital; 🇨🇳 Taichung, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Innovative Cancer Research Institute; 🇺🇸 Whittier, California, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

South Texas Accelerated Research Therapeutics, LLC; 🇺🇸 San Antonio, Texas, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Weill Cornell Medical Center; 🇺🇸 New York, New York, United States

The University of Texas M.D. Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Korea, Republic of

Chonbuk National University Hospital; 🇰🇷 Jeonju, Jeollabuk-do, Korea, Republic of

Severance Hospital, Yonsei University; 🇰🇷 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

Gangnam Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan