A Phase 1/2 Study of ARQ 087 in Adult Subjects with Advanced Solid Tumors with FGFR Genetic Alterations

Phase 1

• Conditions: Advanced Solid Tumors with FGFR Genetic Alterations, Including Intrahepatic Cholangiocarcinoma with FGFR2 Gene Fusion; MedDRA version: 20.1Level: LLTClassification code 10065143Term: Malignant solid tumourSystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10073077Term: Intrahepatic cholangiocarcinomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-001443-36-IT
• Lead Sponsor: ARQULE INC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-08-20
• Last Update Posted: 27 August 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Signed written informed consent granted prior to initiation of any study-specific procedures
2. Male or female subjects of = 18 years of age
3. Histologically or cytologically confirmed locally advanced, inoperable, or metastatic solid tumors. All subjects eligible for enrollment in the Expanded Cohort must have documented and/or confirmed FGFR genetic alterations, including iCCA with FGFR2 gene fusion.
4. Failure to respond to standard therapy, or for whom standard therapy does not exist.
-Subjects enrolled in the Expanded Cohort should have no more than two prior systemic regimens with confirmed disease progression.
-If the subject is refractory or has disease progression within 6 months of adjuvant treatment, then the previous treatment should be considered as a line of treatment rather than adjuvant therapy.
-Subjects who did not receive prior systemic therapy for locally advanced and/or metastatic iCCA with confirmed FGFR2 gene fusion and forwhom, in the opinion of the Investigator, treatment with ARQ 087 is appropriate may be enrolled
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.
-All subjects eligible for enrollment in the Expanded Cohort (Part 2) must have known (documented and/or confirmed) FGFR genetic alterations.
-Archival tumor samples should be collected for all subjects enrolled in the Expanded Cohort. Paired fresh tumor biopsy is optional for subjects enrolled in the Expanded Cohort. Both archival and pre-treatment fresh tumor samples (optional) should be collected prior to the first dose of the study drug.
-All subjects eligible for enrollment in the Food-effect Cohort must have the following tumor types: luminal breast A or B, endometrial, urothelial, gastric, or lung cancer with known and/or confirmed FGFR1-3 high level amplification, mutation or gene rearrangement (fusion, translocation), or adrenocortical carcinoma, cholangiocarcinoma, or sarcomas, independent from FGFR1-3 mutation status
-All subjects eligible for enrollment in the Food-effect Cohort should agree to and be eligible for paired biopsy
7. Life expectancy = 12 weeks
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2
9. Hemoglobin (Hgb) = 9.0 g/dL
10. Absolute neutrophil count (ANC) = 1.5 x 109/L
11. Platelet count = 100 x 109/L
12. Total bilirubin = 1.5 x upper limit of normal (ULN) (= 2 ULN for subjects with cholangiocarcinoma)
13. Aspartate transaminase (AST) and alanine transaminase (ALT) = 3 ULN (= 5 x ULN for subjects with liver metastases)
14. Serum creatinine = 1.5 x ULN or creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
15. Albumin = 2.8 g/dL
16. INR 0.8 to ULN or = 3 for subjects receiving anticoagulant therapy such as Coumadin or heparin
17. Male or female subjects of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after the last dose of ARQ 087
18. Women of childbearing potential must have a negative serum pregnancy test during Screening Period and within 48 hours of the first dose of ARQ 087. Women of childbearing potential” is defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months prior to the first dose of ARQ 087
Are the trial

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 ARQ 087
2. Major surgery or radiation therapy within four weeks of the first dose of ARQ 087
3. Previous treatment with FGFR inhibitors (e.g., ponatinib, dovitinib, nintedanib, AZD4547, NVP-BGJ398, LY2784455, BAY1163877)
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition as ARQ 087
5. Unable or unwilling to swallow the complete daily dose of ARQ 087
6. Clinically unstable central nervous system metastasis (to be eligible, subjects must have stable disease = 3 months, confirmed by MRI or CT scan, and/or have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications)
7. History of 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 ARQ 087 (MI that occurred > 6 monthsprior to the first dose of ARQ 087 will be permitted)
8. Significant gastrointestinal disorder(s) that could, in the opinion of the Investigator, interfere with the absorption, metabolism, or excretion of ARQ 087 (e.g., Crohn’s disease, ulcerative colitis, extensive gastric resection)
9. History and/or current evidence of clinically relevant ectopic mineralization/calcification including but not limited to the soft tissue, kidneys, intestine, myocardium, and lung with the exception of calcified lymph nodes, asymptomatic nephrolithiasis, and asymptomatic coronary calcification (If indicated, standard CT or MRI may be used to assess ectopic mineralization/ calcification.)
10. Previous malignancy within 2 years of the first dose of ARQ 087, except curatively treated non-melanoma skin cancer, carcinoma in-situ of the breast or cervix, 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified