A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ABSK-011 in Patients With Advanced Solid Tumor

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-26

Study Completion Date

2028-12-31

Brief Summary

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This is an open-label phase 1 study with an escalation part and an expansion part.

Detailed Description

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The escalation part will evaluate the safety, tolerability, PK and recommended dose of expansion (RDE) of oral ABSK-011 in patients with advanced solid tumors. The expansion part of oral ABSK-011 at RDE will be followed for further evaluating safety and tolerability in patients with FGF19 overexpression advanced HCC. Preliminary antitumor activity will also be assessed.

Conditions

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Advanced Liver Cancer

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ABSK-011

During the escalation part, all patients will first receive a single dose ABSK-011 (run-in period) at Day -2 and be followed by a 1-day off (2 days in all for run-in period) to access the PK of single-dose. Then, patients will continuously receive ABSK-011 once daily (QD) or twice daily (BID) in repeated 28-day cycles. Dose escalation will employ a "3+3" design except for the patient in the accelerated titration cohort. In expansion part, patients will be treated at the selected RDE dose level.

Group Type EXPERIMENTAL

ABSK-011

Intervention Type DRUG

During the escalation part, the administration of oral ABSK-011 will be guided by "3+3"design based on safety data collected until a maximum tolerated dose (MTD) has been identified. The first dose level will be administered as QD, and different dosing frequencies (e.g., BID) may be explored in subsequent doses depending on emerging safety and pharmacokinetic data. A separate food effect cohort may be conducted. In expansion part, patients will be treated at the selected RDE dose level.

Interventions

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ABSK-011

During the escalation part, the administration of oral ABSK-011 will be guided by "3+3"design based on safety data collected until a maximum tolerated dose (MTD) has been identified. The first dose level will be administered as QD, and different dosing frequencies (e.g., BID) may be explored in subsequent doses depending on emerging safety and pharmacokinetic data. A separate food effect cohort may be conducted. In expansion part, patients will be treated at the selected RDE dose level.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male or female, age 18 \~ 75 (include both ends, or other age range required by local regulations or IRB).
2. Escalation Part: Patients must have histological or cytological confirmed advanced solid tumors that have progressed on or intolerant to standard therapy or whom no standard therapy exists; and patients with advanced HCC must satisfy:

1. BCLC stage B or C and Child-Pugh score 5\~6
2. Patient must provide archived tissue sample or biopsy for FGF19 overexpression central lab testing

Expansion Part: patients must have histological or cytological confirmed, BCLC stage B or C HCC, and have progressed on or intolerant to or have refused to receive or have no access to receive first line systemic therapy (by local guideline/regulation) and is unsuitable for other standard therapy(ies) (by local guideline/regulation) against HCC, and must satisfy:
1. Patient must provide archived tissue sample or biopsy for FGF19 overexpression central lab testing, and the result must be positive
2. Patient must have at least 1 measurable lesion (RECIST V1.1)
3. Child-Pugh score 5\~7 without hepatic encephalopathy, no clinically apparent ascites or require medical intervention
3. ECOG performance status 0\~1
4. Life expectancy ≥ 3 months
5. Adequate organ function and bone marrow function as indicated by the following screening assessments performed within 14 days prior to the first dose of study drug (without blood transfusion or medication with stimulation factors within 14 days before 1st dose):

1. Absolute neutrophil count (ANC) ≥1.5×109/L
2. Platelet count (PLT) ≥75×109/L
3. Hemoglobin (Hb) ≥80 g/L
4. Total bilirubin (TBIL) ≤1.5×ULN
5. Aspartate transaminase (AST) and alanine transaminase (ALT), ≤3×ULN (for patient with liver metastasis in escalation part or patient in expansion part: AST and AST ≤5×ULN)
6. Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (Crcl) ≥50 mL/min based on Cockcroft-Gault formula
6. Patients with HBV infection should follow local clinical practice and anti-HBV therapy should be performed to ensure adequate viral suppression (HBV-DNA \< 10000 IU/mL or equivalent copies/mL prior to enrollment). Patients are examined every cycle to monitor HBV-DNA levels. If virus reactivation occurred for patients without anti-viral treatment when enrolled, anti-HBV therapy will be started following local practice.
7. Non-surgically sterilized male or female patients of childbearing potential must agree to use effective methods of birth control during the study and for up to 6 months after the last dose of study drug. Non-surgically sterilized female patients of childbearing potential must in non-lactation period, and have a negative β-HCG test result within 7 days before first administration.
8. Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.

11. Concomitant use of strong inhibitors or inducers of CYP3A4 (include grapefruit juice, grapefruit hybrids, pomegranates, starfruit, pomelos, Seville oranges or juice or products) within at least 14 day prior to the first dose of the study drug.
12. Impaired cardiac function or clinically significant cardiac disease, including any one of the following:

1. New York Heart Association class III or IV congestive heart failure, unstable angina, or myocardial infarction within 6 months before administration of the study drug;
2. Clinically significant cardiac arrhythmia requiring active therapy;
3. Uncontrolled hypertension;
4. Left ventricle ejection fraction\<50%
5. Prolongation of QTcF (average of three times of examine, male \> 450 ms, female \> 470 ms) (Note: QTc interval corrected by Frederica's formula) at screening, and other ECG abnormalities with clinical significant by the judge of the investigator.
13. Active infection or unexplained fever \> 38.5℃.
14. Active or record of gastrointestinal bleeding within 6 months (e.g. esophageal varices or ulcer bleeding).
15. Patients with active HCV infection (HCV-RNA\>103 copies/mL or following local clinical practice) and require concomitant anti-HCV therapy during the study; or HBV HCV co-infection.
16. History of immunodeficiency, including HIV serum test positive, or other acquired/congenital immunodeficiency disease, or active tuberculosis.
17. Any other clinically significant comorbidities, such as respiratory, metabolic, congenital, endocrine or central nervous system disease, or any other medical conditions, mental disturbances or social determinants, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks.
18. Combined with portal vein tumor thrombus of type IV.

Exclusion Criteria

1. Known allergy or hypersensitivity to any component of the investigational drug product.
2. Previous treatment with FGFR4 or pan-FGFR pathway inhibitors (pan-FGFR inhibitors should be confirmed with the sponsor).
3. Has a known second primary malignancy required active treatment.
4. Has a known active central nervous system (CNS) metastases (if stable disease after treatment, free from or daily dexamethasone \<10 mg or other equivalent glucocorticoids can be enrolled).
5. Liver tumor volume accounts for ≥50% of the whole liver.
6. Inability to take oral medication or other factors significant preclude adequate absorption of oral medication, such as previously received total gastrectomy, residual gastric dysfunction after subtotal gastrectomy, short bowel syndrome after small bowel resection, active diarrhea required drug treatment, etc.
7. Severe irritable bowel syndrome requires drug therapy.
8. Prior organ transplantation requires anti-rejection drug therapy.
9. Previous anti-cancer therapy prior to initiation of study treatment: major surgery (except palliative therapy), radiotherapy (bone-marrow exposure \>30%), routine chemotherapy \<4 weeks (chemotherapy with nitrosourea or mitomycin \<6 weeks); oral chemotherapy, endocrine therapy, molecular targeted therapy or immunotherapy within ≤ 5 half-life or ≤ 4 weeks (whichever is shorter).

Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Xiaoping Chen, Doctor

Role: PRINCIPAL_INVESTIGATOR

Tongji Hospital

Taipei, , Taiwan

Site Status COMPLETED

Countries

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Identifier Type: -

Identifier Source: org_study_id

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ABSK-011 in Patients With Advanced Solid Tumor

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Study Design

Study Groups

ABSK-011

ABSK-011

Interventions

ABSK-011

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

Abbisko Therapeutics Co, Ltd

Responsible Party

Principal Investigators

Xiaoping Chen, Doctor

Locations

Mayo Clinic

Mayo Clinic

Moffitt Cancer Center

Mayo Clinic

Icahn School of Medicine at Mount Sinai

MD Anderson Cancer Center

The First Affiliated Hospital of Bengbu Medical College

Beijing Tsinghua Changgung Hospital

The Fifth Medical Center of the General Hospital of the Chinese People's Liberation Army

Chongqing Cancer Hospital

Fujian Provincial Cancer Hospital

Sun Yat Sen Memorial Hospital

Guangxi Zhuang Autonomous Region People's Hospital

Weifang People's Hospital

Harbin Medical University Cancer Hospital

First Affiliated Hospital of Henan University of Science and Technology

Henan Cancer Hospital

Hubei Cancer Hospital

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

Hunan Cancer Hospital

Hunan Provincial People's Hospital

Suzhou University Affiliated Second Hospital

Tonghua Central Hospital

Shengjing Hospital of China medical university

General Hospital of Ningxia Medical University

Jinan Central Hospital

Linyi Cancer Hospital

The First Affiliated Hospital of Xi'an Jiaotong University

Mianyang Central Hospital

Ningbo Huamei Hospital, University of Chinese Academy of Sciences

National Cheng Kung University Hospitals

Nation Taiwan University Hospital

Countries

Central Contacts

Yuan Lu, Doctor

Facility Contacts

Mitesh J. Borad, MD

Hani M. Babiker, MD

Richard Kim, MD

O'Neke Nickle

Nguyen H. Tran, MD

Max Sung, MD

Sunyoung Lee, MD

Gong Li, Doctor

Dewei Li, Doctor

Yuxian Bai, Doctor

Xiaoping Chen, Doctor

Xiaobo Du, Doctor

Other Identifiers

ABSK-011-101