Clinical trial NCT01752920: Phase 1/2 Study of Derazantinib (ARQ 087) in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations
Official title: A Phase 1/2 Study of ARQ 087 in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations, Including Intrahepatic Cholangiocarcinoma With FGFR2 Gene Fusion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Keywords: FGFR
ARQ 087
Targeted therapy
Molecular therapy
Tyrosine kinase inhibitor
TKI
Receptor tyrosine kinase
RTK
Biomarker
Phase 1
Phase I
Solid tumor
Liver Cancer
Hepatobiliary carcinoma
Biliary tract cancer
Cholangiocarcinoma
Intrahepatic cholangiocarcinoma
FGFR inhibitor
Targeted FGFR kinase inhibitor
Pan-FGFR inhibitor
Selective FGFR inhibitor
FGFR pathway
FGFR signaling
Fibroblast growth factor
FGFR1
FGFR2
FGFR3
FGFR4
FGF
FGF19
FGF21
FGF23
FGFR mutation
FGFR gene fusion
FGFR gene translocation
FGFR genetic aberration
FGFR2 fusion
FGFR2 translocation
Phase 1 Clinical Trial
Phase I Clinical Trial
Clinical oncology
Tumor
Tumour
derazantinib
MK-2921
Lead sponsor: Basilea Pharmaceutica
Sponsor class: INDUSTRY
Collaborators: name: ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
First posted: 2012-12-19
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This was an open-label, Phase 1/2, dose escalation and signal finding study of derazantinib administered to patients with advanced solid tumors (Part 1; Dose Escalation/Food-effect Cohorts) or with advanced solid tumors with FGFR genetic aberrations, including iCCA with FGFR2 gene fusion (Part 2; Expanded Cohort, signal finding).


Eligibility criteria: Inclusion Criteria:

1. Signed written informed consent granted
2. Men or women ≥18 years of age
3. Histologically or cytologically confirmed, locally advanced, inoperable, or metastatic solid tumors. Patients eligible for enrollment in the Expanded Cohort must have documented and/or confirmed FGFR genetic aberrations, including iCCA with FGFR2 gene fusion.
4. Failure to respond to standard therapy, or for whom standard therapy does not exist.
5. Evaluable or measurable disease
6. Archival and/or fresh biopsy tissue samples must be available prior to the first dose of the study drug
7. Life expectancy ≥ 12 weeks
8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
9. Hemoglobin (Hgb) ≥ 9.0 g/dL
10. Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
11. Platelet count ≥ 100 x 10\^9/L
12. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (≤ 2 x ULN for patients with cholangiocarcinoma)
13. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 × ULN (≤ 5 x ULN for patients with liver metastases)
14. Serum creatinine ≤ 1.5 x ULN or creatinine clearance \> 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
15. Albumin ≥ 2.8 g/dL
16. INR 0.8 to ULN or ≤ 3 for patients receiving anticoagulant therapy
17. Men or women of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoid intercourse during the study and for 90 days after the last dose of study drug
18. Women of childbearing potential must have a negative serum pregnancy test during Screening Period and within 48 hours of the first dose of derazantinib.

Exclusion Criteria:

1. Anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks or five times of the drug half life, whichever is longer, of the first dose of derazantinib
2. Major surgery or radiation therapy within four weeks of the first dose of derazantinib
3. Previous treatment with FGFR inhibitors
4. History of allergic reactions attributed to compounds of similar chemical or biological composition as derazantinib
5. Unable or unwilling to swallow the complete daily dose of derazantinib
6. Clinically unstable central nervous system (CNS) metastasis
7. History of myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association classification within 6 months of the first dose of derazantinib (MI occurring \>6 months of the first dose of derazantinib will be permitted)
8. Significant GI disorder(s) that could interfere with the absorption, metabolism, or excretion of derazantinib (e.g. Crohn's disease, ulcerative colitis, extensive gastric resection)
9. History and/or current evidence of clinically relevant ectopic mineralization/calcification
10. Previous malignancy within 2 years prior to the first dose of derazantinib, except curatively treated non-melanoma skin cancer, carcinoma in-situ of the breast or cervix, or superficial bladder tumors
11. Known human immunodeficiency virus (HIV) infection
12. Concurrent uncontrolled illness not related to cancer, including but not limited to:

    * Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements.
    * Uncontrolled diabetes mellitus
13. Blood transfusion within 5 days of the blood draw being used to confirm eligibility
14. Pregnant or breastfeeding

Primary outcomes:
measure: Number of Patients With Drug-related Treatment-emergent Adverse Events (TEAEs)
timeFrame: Adverse events were collected and reported from the time of receiving first dose of derazantinib to the end of study assessment and follow-up period (30-day post-treatment)
Secondary outcomes:
measure: Proportion of Patients With an Objective Tumor Response Per RECIST 1.1
timeFrame: Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated.
measure: Proportion of Patients With Disease Control Per RECIST 1.1
timeFrame: Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated.
measure: Progression-free Survival (PFS)
timeFrame: Assessments were performed at Baseline, and every 8 weeks during continuous drug administration until the End of Treatment visit (7 [+3] days after the last dose of derazantinib) or as otherwise clinically indicated.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Research Institute
state: Arizona
city: Atlanta
country: United States
facility: Emory University, Winship Cancer Institute
state: Georgia
city: Detroit
country: United States
facility: Karmanos Cancer Institute, Detroit
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Bronx
country: United States
facility: Montefiore-Einstein Center for Cancer Care
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: San Antonio
country: United States
facility: START - South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milan
country: Italy
facility: Istituto Clinico Humanitas
city: Milan
country: Italy
facility: Istituto Nazionale Tumori (National Cancer Institute)
city: Padova
country: Italy
facility: Instituto Oncologico Veneto, IRCCS
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana - U.O. Oncologia Medica 2 Univ.
Study officials:
affiliation: Basilea Pharmaceutica
name: Marc Engelhardt, MD
role: STUDY_DIRECTOR
References:
citation: Papadopoulos KP, El-Rayes BF, Tolcher AW, Patnaik A, Rasco DW, Harvey RD, LoRusso PM, Sachdev JC, Abbadessa G, Savage RE, Hall T, Schwartz B, Wang Y, Kazakin J, Shaib WL. A Phase 1 study of ARQ 087, an oral pan-FGFR inhibitor in patients with advanced solid tumours. Br J Cancer. 2017 Nov 21;117(11):1592-1599. doi: 10.1038/bjc.2017.330. Epub 2017 Oct 3.
citation: 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.
citation: Hall TG, Yu Y, Eathiraj S, Wang Y, Savage RE, Lapierre JM, Schwartz B, Abbadessa G. Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation. PLoS One. 2016 Sep 14;11(9):e0162594. doi: 10.1371/journal.pone.0162594. eCollection 2016.