Derazantinib in Subjects With FGFR2 Gene Fusion-, Mutation- or Amplification- Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma

NCT03230318 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: DZB-CS-301ARQ 087-301
• Study Type: interventional
• Target: 148
• Locations: 11 countries
• Sites: 41

Brief Summary

This Phase II, open-label, single-arm study evaluated the anti-cancer activity of derazantinib in subjects with inoperable or advanced intrahepatic cholangiocarcinoma (iCCA) who received at least one prior regimen of systemic therapy. Patients received an oral once-daily total dose of 300 mg derazantinib capsules.

Conditions

Intrahepatic Cholangiocarcinoma; Combined Hepatocellular and Cholangiocarcinoma

Keywords

iCCA; intrahepatic cholangiocarcinoma; FGFR2 gene fusion or FGFR2 gene mutation or amplification; biliary cancer; bile duct cancer; FGFR2 gene rearrangement; liver cancer; targeted therapy; combined hepatocellular and cholangiocarcinoma; cHCC-CCA; derazantinib

Outcome Measures

Primary Outcomes (2)

• Substudy 1: Objective Response Rate (ORR)

  ORR was defined as the proportion of patients who achieved a confirmed clinical response (CR) or partial response (PR) by blinded independent central review using the internationally recognized criteria for the radiological assessment in tumor response of solid tumors (RECIST) Version 1.1

  From first dose and up to 54 months

• Substudy 2: Progression Free Survival at 3 Months (PFS 3)

  PFS3 was defined as the proportion of patients who have progression-free survival at 3 months from the first date of receiving study drug as assessed by survival status and blinded independent central review as per RECIST 1.1.

  From first dose and up to 3 months

Secondary Outcomes (5)

• PFS

  From first dose and up to 54 months

• Overall Survival (OS)

  From first dose and up to 54 months

• Duration of Response (DoR)

  From first dose and up to 54 months

• Substudy 2: Objective Response Rate

  From first dose and up to 54 months

• Number of Patients With Grade 3-5 Treatment-emergent Adverse Events (TEAEs)

  TEAEs were defined as all events occurring after drug treatment began and up to 30 days after last study drug administration

Study Arms (1)

derazantinib

EXPERIMENTAL

Oral administration

Drug: derazantinib

Interventions

derazantinib DRUG

Derazantinib was administered orally at 300 mg once daily

derazantinib

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent granted prior to initiation of any study-specific procedures
• years of age or older
• Histologically or cytologically confirmed locally advanced, inoperable, or metastatic iCCA or mixed histology tumors
• Substudy 1:
• FGFR2 fusion status based on the following assessments:
• a) If central laboratory was designated by Sponsor: Positive FISH test; and/or b) If non-central laboratory: i) Positive FISH or NGS test: patients were potentially enrolled and started dosing, but central confirmation was required\* ii) Negative FISH or NGS test: tissue was submitted to the central laboratory designated by the Sponsor, and patients were only enrolled in case the central test was positive
• \*By used standard protocols and approved by local IRB/EC, by CLIA or other similar agency.
• Substudy 2:
• FGFR2 mutation/amplification status based on local NGS testing performed or commissioned by the respective study site.
• Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression
• Measurable disease by RECIST version 1.1 criteria
• ECOG performance status ≤ 1
• Adequate organ functions as indicated by the following laboratory values (based on screening visit values from the central laboratory).
• Hematological
• Hemoglobin (Hgb) ≥ 9.0 g/dL

You may not qualify if:

• Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable:
• One chemotherapy or biological (e.g., antibody) cycle interval
• Five half-lives of any small-molecule investigational or licensed medicinal product
• Two weeks, for any investigational medicinal product with an unknown half-life
• Four weeks of curative radiotherapy
• Seven days of palliative radiotherapy
• days of radiotherapy
• Major surgery, locoregional therapy, or radiation therapy within four weeks of the first dose of derazantinib
• Previous treatment with any FGFR inhibitor (e.g., Balversa® \[erdafitinib\], Pemazyre® \[pemigatinib\], infigratinib, rogaratinib, futibatinib, lenvatinib, ponatinib, dovitinib, nintedanib, AZD4547, LY2784455).
• Patients who were unable or unwilling to swallow the complete daily dose of derazantinib capsules
• Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects must had stable disease ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or had CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications)
• Evidence of clinically significant corneal or retinal disorder which was likely to increase the risk of eye toxicity, including but not limited to bullous/band keratopathy, keratoconjunctivitis (unless keratoconjunctivitis sicca), corneal abrasion, inflammation/ulceration, confirmed by ophthalmologic examination.
• Uncontrolled or active hepatobiliary disorders, untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, biloma or abscess (to be eligible, the subjects had to be treated and disorders/complications should had been resolved within 2 weeks prior to the first dose of derazantinib)
• History of significant cardiac disorders:
• Myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of derazantinib (MI that occurred \> 6 months prior to the first dose of derazantinib was permitted)

Sponsors & Collaborators

• Basilea Pharmaceutica: lead

Study Sites (41)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612-9416, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center - Sidney Kimmel Center for Prostate and Urologic Cancers

New York, New York, 10065-6800, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Washington Medical Center

Seattle, Washington, 98109, United States

Location

Hôpital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

CHU Grenoble Alpes

La Tronche, 38700, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, 60590, Germany

Location

Universitätsklinikum Hamburg-Eppendorf (UKE)

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover (MHH)

Hanover, 30625, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, 66421, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

St. James's Hospital

Dublin, D08 NHY1, Ireland

Location

Sant'Orsola-Malpighi Hospital, University of Bologna

Bologna, 40138, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Ospedale San Gerardo

Monza, 20900, Italy

Location

Istituto Oncologico Veneto - IRCCS

Padua, 35128, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, 56126, Italy

Location

Humanitas Cancer Center, Istituto Clinico Humanitas IRCCS

Rozzano, 20089, Italy

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 6591, South Korea

Location

Vall d'Hebrón University Hospital

Barcelona, 08035, Spain

Location

Catalan Institute of Oncology

Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Universitätsspital Basel

Basel, 4031, Switzerland

Location

University College London Hospitals NHS Foundation Trust

Euston, NW1 2BU, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G120YN, United Kingdom

Location

The Royal Marsden

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Mazzaferro V, El-Rayes BF, Droz Dit Busset M, Cotsoglou C, Harris WP, Damjanov N, Masi G, Rimassa L, Personeni N, Braiteh F, Zagonel V, Papadopoulos KP, Hall T, Wang Y, Schwartz B, Kazakin J, Bhoori S, de Braud F, Shaib WL. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma. Br J Cancer. 2019 Jan;120(2):165-171. doi: 10.1038/s41416-018-0334-0. Epub 2018 Nov 13.

  PMID: 30420614 DERIVED

MeSH Terms

Conditions

Cholangiocarcinoma; Liver Neoplasms; Biliary Tract Neoplasms; Bile Duct Neoplasms

Interventions

derazantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases

Results Point of Contact

• Title: Dr Manuel Häckl, MD
• Organization: Basilea Pharmaceutica International Ltd, Allschwil

manuel.haeckl@basilea.com

+41 76 302 53 10

Study Officials

• Manuel Häckl, MD

  Basilea Pharmaceutica International Ltd, Allschwil

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 24, 2017
• First Posted: July 26, 2017
• Study Start: September 28, 2017
• Primary Completion: October 25, 2022
• Study Completion: October 25, 2022
• Last Updated: December 19, 2023
• Results First Posted: December 19, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); KR (3); CA (2); IT (6); US (11); FR (2); DE (5); IE (1); CH (1); ES (4); BE (3)