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

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01752920
• Other study ID #: ARQ 087-101
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 10, 2012
• Est. completion date: August 28, 2018

Study information

• Verified date: May 2023
• Source: Basilea Pharmaceutica
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: August 28, 2018
• Est. primary completion date: August 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Solid Tumor

Intervention

Drug:
• Derazantinib low dose range
Derazantinib was administered orally at dose levels from 25 mg QOD - 200 mg QD on a 28-day schedule.
• Derazantinib middle dose range
Derazantinib was administered orally at dose levels from 250 mg QD - 325 mg QD on a 28-day schedule.
• Derazantinib high dose range
Derazantinib was administered orally at dose levels from 400 mg QD - 425 mg QD on a 28-day schedule.
• Derazantinib at recommended phase 2 dose (RP2D)
Derazantinib was administered orally at the recommended phase 2 dose of 300 mg QD on a 28-day schedule.

Locations

Country	Name	City	State
Italy	Istituto Clinico Humanitas	Milan
Italy	Istituto Nazionale Tumori (National Cancer Institute)	Milan
Italy	Instituto Oncologico Veneto, IRCCS	Padova
Italy	Azienda Ospedaliero-Universitaria Pisana - U.O. Oncologia Medica 2 Univ.	Pisa
United States	Emory University, Winship Cancer Institute	Atlanta	Georgia
United States	Montefiore-Einstein Center for Cancer Care	Bronx	New York
United States	Karmanos Cancer Institute, Detroit	Detroit	Michigan
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	START - South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	Scottsdale Healthcare Research Institute	Scottsdale	Arizona
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Basilea Pharmaceutica	ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Countries where clinical trial is conducted

United States,  Italy, 

References & Publications (2)

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 advan — View 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 sol — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Proportion of Patients With an Objective Tumor Response Per RECIST 1.1	The number of patients with an objective tumor response, which included those with either a complete response (CR) or a partial response (PR) based on RECIST v1.1 guidelines which defines criteria for the radiological assessment in tumor response.; The objective response rate (ORR) was defined as the proportion of patients with a CR or PR.	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.
Secondary	Proportion of Patients With Disease Control Per RECIST 1.1	The number of patients with tumor disease control, which included those with either a complete or partial tumor response, or a stable disease (SD) based on RECIST v1.1 guidelines which defines criteria for the radiological assessment in tumor response. The disease control rate (DCR) was defined as the proportion of patients with CR, PR or SD.	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.
Secondary	Progression-free Survival (PFS)	PFS was calculated as the time from the date of first dose until documented radiographic disease progression or death from any cause, whichever occurred first. Disease progression is measured according to a specified radiologic increase in tumor size.	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.