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).
Brief Title
Phase 1/2 Study of Derazantinib (ARQ 087) in Adult Subjects With Advanced Solid Tumors With FGFR Genetic Alterations
Categories
Completion Date
Completion Date Type
Actual
Conditions
Solid Tumor
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
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
Inclusion 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.
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.
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01752920
Org Class
Industry
Org Full Name
Basilea Pharmaceutica
Org Study Id
ARQ 087-101
Overall Status
Completed
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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)
Outcome Measure
Number of Patients With Drug-related Treatment-emergent Adverse Events (TEAEs)
Outcome Time Frame
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
Outcome Description
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.
The objective response rate (ORR) was defined as the proportion of patients with a CR or PR.
Outcome Time Frame
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.
Outcome Measure
Proportion of Patients With an Objective Tumor Response Per RECIST 1.1
Outcome Description
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.
Outcome Time Frame
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.
Outcome Measure
Proportion of Patients With Disease Control Per RECIST 1.1
Outcome Description
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.
Outcome Time Frame
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.
Outcome Measure
Progression-free Survival (PFS)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Andreas Kaubisch
Investigator Email
akaubisc@montefiore.org
Investigator Phone
718-920-7100
Categories Mesh Debug
Cancer --- NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Digestive System --- LIVER DISEASES
Liver --- LIVER DISEASES
Digestive System --- BILIARY TRACT DISEASES
Liver --- BILIARY TRACT DISEASES
Endocrine System Cancers --- ADENOCARCINOMA
Cancer --- CARCINOMA
Lung & Chest Cancers --- NEOPLASMS, GLANDULAR AND EPITHELIAL
MeSH Terms
LIVER NEOPLASMS
BILIARY TRACT NEOPLASMS
CHOLANGIOCARCINOMA
NEOPLASMS
DIGESTIVE SYSTEM NEOPLASMS
NEOPLASMS BY SITE
DIGESTIVE SYSTEM DISEASES
LIVER DISEASES
BILIARY TRACT DISEASES
ADENOCARCINOMA
CARCINOMA
NEOPLASMS, GLANDULAR AND EPITHELIAL
NEOPLASMS BY HISTOLOGIC TYPE
DERAZANTINIB