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

NCT ID: NCT01752920

Last Updated: 2023-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 119 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-10
• Study Completion Date: 2018-08-28

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low Dose Group

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.

Group Type: EXPERIMENTAL

Derazantinib low dose range

Intervention Type: DRUG

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

Middle Dose Group

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.

Group Type: EXPERIMENTAL

Derazantinib middle dose range

Intervention Type: DRUG

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

High Dose Group

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.

Group Type: EXPERIMENTAL

Derazantinib high dose range

Intervention Type: DRUG

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

Expanded Cohort Group

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.

Group Type: EXPERIMENTAL

Derazantinib at recommended phase 2 dose (RP2D)

Intervention Type: DRUG

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

Interventions

Derazantinib low dose range

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

Intervention Type: DRUG

Derazantinib middle dose range

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

Intervention Type: DRUG

Derazantinib high dose range

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

INDUSTRY

Sponsor Role: collaborator

Basilea Pharmaceutica

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Engelhardt, MD

Role: STUDY_DIRECTOR

Basilea Pharmaceutica

Locations

Scottsdale Healthcare Research Institute

Scottsdale, Arizona, United States

Emory University, Winship Cancer Institute

Atlanta, Georgia, United States

Karmanos Cancer Institute, Detroit

Detroit, Michigan, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Montefiore-Einstein Center for Cancer Care

The Bronx, New York, United States

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

START - South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, United States

University of Washington

Seattle, Washington, United States

Istituto Clinico Humanitas

Milan, , Italy

Istituto Nazionale Tumori (National Cancer Institute)

Milan, , Italy

Instituto Oncologico Veneto, IRCCS

Padua, , Italy

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

Pisa, , Italy

Countries

United States; Italy

References

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.

Reference Type: RESULT

PMID: 28972963 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30420614 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27627808 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ARQ 087-101

Identifier Type: -

Identifier Source: org_study_id