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

NCT02318329 | Completed Phase 1 Results DMC

• 1 other identifier: FPA144-001
• Study Type: interventional
• Target: 79
• Locations: 3 countries
• Sites: 26

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.

Conditions

Advanced Solid Tumors; Gastric Cancer; Transitional Cell Carcinoma of the Bladder

Keywords

FGFR2b, FGFR2, FGFR, bladder neoplasms, esophageal cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Pharmacokinetic (PK) Profile of FPA144: Maximum Serum Concentration

  16 weeks on average

• Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  16 weeks on average

• Duration of Response Per RECIST 1.1 (Part 2 Only)

  16 weeks on average

• Pharmacokinetic (PK) Profile of FPA144: Area Under Serum Concentration-time Curve

  16 weeks on average

Study Arms (3)

Part 1A: FPA144 Dose Escalation Solid Tumors

EXPERIMENTAL

Dose escalation of FPA144 (0.3 mg/kg to 15 mg/kg)

Drug: FPA144

Part 1B: FPA144 Dose Escalation Gastric Cancer

EXPERIMENTAL

Dose escalation of FPA144 (3-10 mg/kg) in patients with gastric cancer

Drug: FPA144

Part 2: FPA144 Dose Expansion Gastric or Other Solid Tumors

EXPERIMENTAL

Evaluation of objective responses in patients with tumors with various levels of FGFR2b overexpression

Drug: FPA144

Interventions

FPA144 DRUG

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

Also known as: Bemarituzumab

Part 1A: FPA144 Dose Escalation Solid Tumors; Part 1B: FPA144 Dose Escalation Gastric Cancer; Part 2: FPA144 Dose Expansion Gastric or Other Solid Tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Five Prime Therapeutics, Inc.: lead

Study Sites (26)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center, Mission Bay

San Francisco, California, 74158, United States

Location

Innovative Cancer Research Institute

Whittier, California, 90603, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Weill Cornell Medical Center

New York, New York, 10065, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Sarah Cannon Research Institute, LLC

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

Chonbuk National University Hospital

Jeonju, Jeollabuk-do, 561-712, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 463-707, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Severance Hospital, Yonsei University

Seoul, 120-752, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Gangnam Severance Hospital

Seoul, 135-720, South Korea

Location

Korea University Anam Hospital

Seoul, 136-705, South Korea

Location

Seoul St. Mary's Hospital

Seoul, 137-701, South Korea

Location

SMG-SNU Boramae Medical Center

Seoul, 156-707, South Korea

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Related 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.

  PMID: 31094225 BACKGROUND

• 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.

  PMID: 32167861 BACKGROUND

• 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.

  PMID: 32965540 BACKGROUND

MeSH Terms

Conditions

Stomach Neoplasms; Urinary Bladder Neoplasms; Esophageal Neoplasms

Interventions

bemarituzumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Head and Neck Neoplasms; Esophageal Diseases

Limitations and Caveats

Inclusion of patients with refractory gastric cancer with short duration of drug exposure may have limited our ability to accurately evaluate the incidence of off-target effects adverse events in the study population, in particular corneal toxicity.

Results Point of Contact

• Title: Medical Lead
• Organization: Five Prime Therapeutics

FPA144@fiveprime.com

415-365-5600

Study Officials

• Medical Lead

  Five Prime Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2014
• First Posted: December 17, 2014
• Study Start: November 1, 2014
• Primary Completion: February 28, 2019
• Study Completion: June 30, 2019
• Last Updated: June 4, 2024
• Results First Posted: March 11, 2020

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After publication of the primary endpoint results.
• Access Criteria: Participating investigators in good standing.

Locations

US (13); KR (9); TW (4)