Inoperable or advanced FGFR2 gene fusion positive intrahepatic cholangiocarcinoma MedDRA version: 20.0 Level: LLT Classification code 10073078 Term: Intrahepatic cholangiocarcinoma recurrent System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10073077 Term: Intrahepatic cholangiocarcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: ARQ 087
Product Code: ARQ 087
Pharmaceutical Form: Capsule, hard
CAS Number: 1821329-75-2
Current Sponsor code: ARQ 087
Other descriptive name: ARQ 087•2HCl
Concentration unit: mg millig
Sponsors
ARQULE INC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Tissue samples for genetic testing will be obtained from subjects who meet the following pre-screening eligibility criteria: 1. Signed written informed consent to permit tissue analysis 2. 18 years of age or older 3. No medical history that is excluded per the study treatment eligibility criteria 4. Eastern Cooperative Oncology Group (ECOG) performance status = 1 (Appendix 2 of the protocol) 5. Eligible for or receiving systemic therapy for inoperable or advanced iCCA 6. Not currently eligible for curative local or surgical therapy To be enrolled in the study, once the FGFR2 gene fusion status is determined, each prospective subject must meet all of the following inclusion criteria: 1. Signed written informed consent granted prior to initiation of any study-specific procedures 2. 18 years of age or older 3. Histologically or cytologically confirmed locally advanced, inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons), or metastatic iCCA or mixed histology tumors (combined hepatocellular-cholangiocarcinoma [cHCC-CCA]) 4. FGFR2 gene fusion status confirmed by NGS or FISH testing - Test positive by FISH by the central laboratory designated by the Sponsor - Have FGFR2 gene fusion documented by a local or central laboratory using standard protocols and approved by local IRB/IEC, Clinical Laboratory Improvement Amendments (CLIA), or other similar agency. If the FGFR2 gene fusion is identified by a laboratory other than the Sponsor’s central laboratory, then archival and/or recent tissue biopsy samples or a tissue block suitable for genetic testing must be available for confirmatory testing by FISH by the Sponsor’s central laboratory (Refer to Section 6.7 and the Laboratory Manual for tissue preparation requirements). If a subject has documentation from a local or central laboratory indicating that they test negative for FGFR2 gene fusion, that subject may not be enrolled in the study. 5. Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression or was not able to tolerate prior systemic therapy. - if the subject received at least 4 cycles of systemic therapy and no measurable tumor reduction compared to the previous scan is observed, such subject can be enrolled - if the subject received immunotherapy, the documented radiographic disease progression is required - if the subject experienced disease progression within 6 months of adjuvant therapy, such therapy should be considered as the line of treatment rather than adjuvant therapy 6. Measurable disease by RECIST version 1.1 criteria 7. ECOG performance status = 1 (Appendix 2) 8. Adequate organ functions as indicated by the following laboratory values (based on screening visit values from the central laboratory). - Hematological ? Hemoglobin (Hgb) = 9.0 g/dL ? Absolute neutrophil count (ANC) = 1.5 x 10*9/L ? Platelet count = 75 x 10*9/L ? International normalized ratio (INR) 0.8 to upper limit of normal (ULN) or = 3 for subjects receiving anticoagulant therapy such as Coumadin or heparin - Hepatic ? Total bilirubin = 2 x ULN ? Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 ULN (= 5 x ULN for subjects with liver metastases) ? Albumin = 2.8 g/dL - Renal ? Serum creatinine = 1.5 x ULN ? Creatinine clearance of = 60 mL/min as estimated by the Cockcroft-Gault equation 9. Male or female subjects of child-producing potential must agree to use double-
Exclusion criteria
Exclusion criteria: 1. Systemic anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal, targeted therapy, or investigational agents within four weeks of the first dose of ARQ 087 2. Major surgery, locoregional therapy, or radiation therapy within four weeks of the first dose of ARQ 087 3. Previous treatment with any FGFR inhibitor (e.g., ponatinib, dovitinib, nintedanib, AZD4547, NVP-BGJ398, LY2784455, BAY1163877) - Subjects who received less than four weeks of therapy and were unable to continue therapy due to toxicity will be allowed to participate 4. Unable or unwilling to swallow the complete daily dose of ARQ 087 capsules 5. Clinically unstable central nervous system (CNS) metastases (to be eligible, subjects must have stable disease = 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and/or have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications) 6. Current evidence of corneal or retinal disorder, including but not limited to bullous/band keratopathy, keratoconjunctivitis, corneal abrasion, inflammation/ulceration, confirmed by ophthalmologic examination 7. Concurrent uncontrolled or active hepatobiliary disorders, untreated or ongoing complications after laparoscopic procedures or stent placement, including but not limited to active cholangitis, biloma or abscess (to be eligible, the subjects have to be treated and disorders/complications should be resolved within 2 weeks prior to the first dose of ARQ 087) 8. History of significant cardiac disorders: - 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 months prior to the first dose of ARQ 087 will be permitted) - QTcF > 500 msec (males or females) 9. 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) 10. Previous malignancy within 2 years of the first dose of ARQ 087, except curatively treated or low grade malignancies such as non-melanoma skin cancer, carcinoma in-situ of the breast, cervix, and superficial bladder tumors 11. 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 - Known uncontrolled human immunodeficiency virus (HIV) infection 12. Blood or albumin transfusion within 5 days of the blood draw being used to confirm eligibility 13. Pregnant or breast feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Tumor assessments (CT or MRI scan) of the chest, abdomen, and pelvis will be done at screening, once every 8 weeks (every 2 cycles) from the day of the first dose for the first 6 cycles (C3D1, C5D1, C7D1), and once every 12 weeks (every 3 cycles) thereafter (C10D1, C13D1, etc.). The End of Treatment scan will be done if the previous scan was not done within four weeks (28 days) prior to the End of Treatment visit or if the previous scan did not show radiographic disease progression.;Main Objective: To evaluate the anti-cancer activity by Objective Response Rate (ORR) by central radiology review as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in subjects with inoperable or advanced iCCA whose tumors harbor FGFR2 gene fusions (by FISH performed by a central laboratory) and who received at least one prior regimen of systemic therapy;Secondary Objective: • To evaluate progression free survival (PFS) by central radiology review and overall survival (OS) • To evaluate duration of response (DoR) by central radiology review • To evaluate the safety profile (toxicities) of ARQ 087 in this subject population;Primary end point(s): ORR will be the proportion of subjects with confirmed complete responses and partial responses by central radiology review as per RECIST version 1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • DoR will be calculated from the first date of documented tumor response to disease progression by central radiology review • PFS will be calculated from the first date of receiving study drug until radiographic disease progression by central radiology review or death • OS will be calculated from the first date of receiving study drug until death;Timepoint(s) of evaluation of this end point: DoR and PFS: Tumor assessments (CT or MRI scan) of the chest, abdomen, and pelvis will be done every 8 weeks (every 2 cycles) from the day of the first dose for the first 6 cycles (C3D1, C5D1, C7D1) and once every 12 weeks (every 3 cycles) thereafter (C10D1, C13D1, etc.). The End of Treatment scan will be done if the previous scan was not done within four weeks (28 days) prior to the End of Treatment visit or if the previous scan did not show radiographic disease progression. OS: from the first date of receiving study drug until death. | — |
Countries
Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactManager, RA/QA
ArQule, Inc.
Outcome results
None listed