Phase 1/2 Study of Derazantinib (ARQ 087) in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations

NCT01752920 | Completed Phase 1 Results FDA Drug

• 1 other identifier: ARQ 087-101
• Study Type: interventional
• Target: 119
• Locations: 2 countries
• Sites: 12

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).

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

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Drug-related Treatment-emergent Adverse Events (TEAEs)

  Adverse events were graded for severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. CTCAE is classifying AEs and their associated severity from Grade 1 (Mild AE), Grade 2 (Moderate AE), Grade 3 (Severe or medically significant but not immediately life-threatening), Grade 4 (Life-threatening consequences) to Grade 5 (Death related to AE)

  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 (3)

• Proportion of Patients With an Objective Tumor Response Per RECIST 1.1

  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.

• Proportion of Patients With Disease Control Per RECIST 1.1

  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.

• Progression-free Survival (PFS)

  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.

Study Arms (4)

Low Dose Group

EXPERIMENTAL

Patients who received derazantinib orally at dose levels from 25 mg every other day (QOD) - 200 mg daily (QD) on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Drug: Derazantinib low dose range

Middle Dose Group

EXPERIMENTAL

Patients who received derazantinib orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Drug: Derazantinib middle dose range

High Dose Group

EXPERIMENTAL

Patients who received derazantinib orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Drug: Derazantinib high dose range

Expanded Cohort Group

EXPERIMENTAL

Patients who received derazantinib orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule until documented progression of disease (clinical or radiological), unacceptable toxicity, or another of the discontinuation criteria.

Drug: Derazantinib at recommended phase 2 dose (RP2D)

Interventions

Derazantinib low dose range DRUG

Derazantinib was administered orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule.

Low Dose Group

Derazantinib middle dose range DRUG

Derazantinib was administered orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule.

Middle Dose Group

Derazantinib high dose range DRUG

Derazantinib was administered orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule.

High Dose Group

Derazantinib at recommended phase 2 dose (RP2D) DRUG

Derazantinib was administered orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule.

Expanded Cohort Group

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
• Men or women ≥18 years of age
• 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.
• Failure to respond to standard therapy, or for whom standard therapy does not exist.
• Evaluable or measurable disease
• Archival and/or fresh biopsy tissue samples must be available prior to the first dose of the study drug
• Life expectancy ≥ 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Hemoglobin (Hgb) ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelet count ≥ 100 x 10\^9/L
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (≤ 2 x ULN for patients with cholangiocarcinoma)
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 × ULN (≤ 5 x ULN for patients with liver metastases)
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance \> 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Albumin ≥ 2.8 g/dL

You may not qualify if:

• 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
• Major surgery or radiation therapy within four weeks of the first dose of derazantinib
• Previous treatment with FGFR inhibitors
• History of allergic reactions attributed to compounds of similar chemical or biological composition as derazantinib
• Unable or unwilling to swallow the complete daily dose of derazantinib
• Clinically unstable central nervous system (CNS) metastasis
• 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)
• 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)
• History and/or current evidence of clinically relevant ectopic mineralization/calcification
• 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
• Known human immunodeficiency virus (HIV) infection
• 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
• Blood transfusion within 5 days of the blood draw being used to confirm eligibility

Sponsors & Collaborators

• Basilea Pharmaceutica: lead
• ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA): collaborator

Study Sites (12)

Scottsdale Healthcare Research Institute

Scottsdale, Arizona, 85258, United States

Location

Emory University, Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Karmanos Cancer Institute, Detroit

Detroit, Michigan, 48201, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Montefiore-Einstein Center for Cancer Care

The Bronx, New York, 10467, United States

Location

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

START - South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Istituto Clinico Humanitas

Milan, 20089, Italy

Location

Istituto Nazionale Tumori (National Cancer Institute)

Milan, 20133, Italy

Location

Instituto Oncologico Veneto, IRCCS

Padua, 35128, Italy

Location

Azienda Ospedaliero-Universitaria Pisana - U.O. Oncologia Medica 2 Univ.

Pisa, 56126, Italy

Location

Related Publications (3)

• 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.

  PMID: 28972963 RESULT

• 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 RESULT

• 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.

  PMID: 27627808 DERIVED

MeSH Terms

Conditions

Liver Neoplasms; Biliary Tract Neoplasms; Cholangiocarcinoma; Neoplasms

Interventions

derazantinib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Basilea Pharmaceutica International Ltd.

marc.engelhardt@basilea.com

+41 79 701 0551

Study Officials

• Marc Engelhardt, MD

  Basilea Pharmaceutica

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: December 14, 2012
• First Posted: December 19, 2012
• Study Start: December 10, 2012
• Primary Completion: August 28, 2018
• Study Completion: August 28, 2018
• Last Updated: June 5, 2023
• Results First Posted: October 28, 2021

Record last verified: 2023-05

Locations

IT (4); US (8)