Trial Title:
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK121-NX in Patients With Advanced Solid Tumors
NCT ID:
NCT05627063
Condition:
Solid Tumor
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ABSK121-NX
Description:
In the escalation part, patients will receive a single dose of oral ABSK121-NX on Day -7
followed by a 7-day washout (Day -7 dosing day as 1st day of wash out) as a run-in period
to access the safety and PK of ABSK121-NX. Then, patients will continuously receive
ABSK121-NX once daily (QD) starting at C1D1 and continuing in subsequent cycles (28-day
cycles). The starting dose is 3mg QD. In the expansion part, patients will each receive
oral ABSK121-NX at the RDE in repeated 28-day cycles.
Arm group label:
ABSK121-NX
Summary:
This is an open-label phase 1 study with expansion. The study will start with a dose
escalation of single-agent ABSK121-NX administered in repeated 28-day cycles in patients
with advanced solid tumors to evaluate safety and tolerability. The expansion part will
investigate oral ABSK121-NX at the recommended dose for expansion (RDE) to further
evaluate safety and tolerability among selected tumor types. Preliminary antitumor
activity will also be assessed.
Detailed description:
Escalation Part:
Dose escalation of oral ABSK121-NX will be guided by the Bayesian optimal interval (BOIN)
design based on safety data collected until a maximum tolerated dose (MTD) or maximum
administered dose (MAD) has been identified. During the dose escalation part of the
study, patients will receive a single dose of ABSK121 on Day -7 followed by a 7-day
washout (Day -7 dosing day as 1st day of wash out) as a run-in period to access the
safety and PK of ABSK121-NX. Then, patients will continuously receive ABSK121-NX once
daily (QD) beginning at C1D1.
The dose escalation will start at 3 mg QD followed by dose escalation of a total of 8
potential dose levels. Once RDE is determined, an RDE-confirmation group of up to 24 more
patients may be enrolled at the selected dose levels to further evaluate safety and
efficacy (up to 12 per dose level/regimen), if approved by the sponsor. In addition, a
preliminary food-effect (FE) may be evaluated in Cycle 1 D15 or later in at least 6
patients from the RDE- confirmation part.
After the RDE is determined in the dose escalation part, the dose expansion phase will be
conducted.
Expansion Part:
When health authorities outside US require that the safety data in the local population
be provided prior to the expansion part, a minimum of 3 local subjects will be enrolled
and treated at the selected RDE dose level first in that country/region to evaluate the
tolerability of ABSK121-NX. The inclusion and exclusion criteria for escalation part will
apply for these subjects. After similar safety and tolerability of ABSK121-NX in patients
in the relevant locality have been confirmed by local Investigators and the Sponsor,
additional patients will be allowed to enroll in the expansion part.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients should understand, sign, and date the written informed consent form prior
to screening
2. Male or female age 18 years or older
3. Patients with histologically confirmed locally-advanced or metastatic solid tumors
who have progressed on, or are intolerant of standard therapy, or for whom no
standard therapy exists, or reject standard therapy
For RDE-confirmation in the escalation part: patients with selected advanced solid
tumors, i.e.,
1. Patients must have the following FGFR genetic alterations based on central
laboratory tests or existing test reports of tumor tissue and/or blood:
1. Urothelial carcinoma (UC): pre-specified FGFR3 mutations (R248C, S249C, G370C,
Y373C) or FGFR2/3 fusions (partner gene is previously described or in frame),
or
2. Intrahepatic Cholangiocarcinoma (iCCA): FGFR2 fusions or rearrangements which
containing an intact kinase domain as follows:
• FGFR2 fusions: FGFR2 rearrangements with a literature-derived known partner
gene regardless of strand or frame, or FGFR2 rearrangements in the same 5' to
3' orientation and in frame with a novel partner gene
• FGFR2 rearrangements: FGFR2 rearrangements with one breakpoint in the hotspot
region (intron 17-exon 18) and the other breakpoint in an intergenic region or
within another gene, or intragenic duplication of the kinase domain (exon 9-17)
2. Patients must have at least one measurable target lesion according to RECIST 1.1
For the expansion Part:
1) Patients must have the following FGFR genetic alterations based on central
laboratory tests or existing test reports of tumor tissue and/or blood:
1. Urothelial carcinoma: pre-specified FGFR3 mutations (R248C, S249C, G370C, Y373C) or
FGFR2/3 fusions (partner gene is previously described or in frame)
2. Cholangiocarcinoma: FGFR2 fusions or rearrangements which containing an intact
kinase domain as follows:
- FGFR2 fusions: FGFR2 rearrangements with a literature-derived known partner
gene regardless of strand or frame, or FGFR2 rearrangements in the same 5' to
3' orientation and in frame with a novel partner gene
- FGFR2 rearrangements: FGFR2 rearrangements with one breakpoint in the hotspot
region (intron 17-exon 18) and the other breakpoint in an intergenic region or
within another gene, or intragenic duplication of the kinase domain (exon 9-17)
3. Other tumor types: solid tumors harboring FGFR1-4 alterations including activating
mutations, fusions or rearrangements and amplifications, e.g., advanced/metastatic
gastric cancer (GC) or gastroesophageal junction (GEJ) carcinoma harboring the FGFR2
amplifications, or iCCA patients or UC patients with other FGFR alterations not
mentioned above, are also allowed
2) Patients must have at least one measurable target lesion according to RECIST
1.1
3) Previous FGFR inhibitors treated and progressed cohort in UC or iCCA patients:
received treatment with FGFR inhibitors and experienced disease
progression/recurrence during or after FGFR inhibitors treatment
4. ECOG performance status 0 or 1
5. Life expectancy ≥3 months
6. 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:
1. Absolute neutrophil count (ANC) ≥1.5×109/L (without the use of hematopoietic
colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF) within 7 days
before testing)
2. Platelet count (PLT) ≥100×109/L (without transfusion within 14 days before
testing)
3. Hemoglobin (Hb) ≥90 g/L (without transfusion within 7 days before testing)
4. Total bilirubin (TBIL) ≤1×ULN
5. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5×ULN
6. Creatinine clearance (Crcl) ≥60 mL/min based on Cockcroft-Gault formula
7. Electrolyte: magnesium within 0.85 to 1.25 × institutional normal limits,
sodium ≥130 mmol/L, potassium within institutional normal limits 7. For
patients participating exploration of food effect:
1. be able to eat a standardized high-fat, high caloric meal within 30 minutes
2. be able to fast for 10 hours
Exclusion Criteria:
1. Known allergy or hypersensitivity to any component of the investigational
product
2. RDE-confirmation in Escalation part: Prior treatment with any FGFR inhibitors
3. Expansion part:
1. Previously FGFR-inhibitors naive cohorts in UC or iCCA patients: Prior
treatment with any FGFR inhibitors
2. Other solid tumors cohort: Prior treatment with any FGFR inhibitors
4. Has a known additional malignancy that is progressing or has required active
treatment.
5. Has persistent phosphate level >ULN during screening (within 14 days prior to
the first dose of study treatment) and despite medical management
6. Unable to swallow capsules or tablets or malabsorption syndrome, disease
significantly affecting GI function, or resection of the stomach or small
bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial
or complete bowel obstruction. If any of these conditions exist, the site
should discuss with the sponsor to determine patient eligibility
7. Previous anti-cancer therapy, including chemotherapy (chemotherapy with
nitrosourea or mitomycin received ≤ 6 weeks prior to initiation of study
treatment), radiotherapy, molecular targeted therapy, antibody therapy or other
investigational drugs received ≤4 weeks; endocrine therapy ≤2 weeks or ≤5
half-lives (whichever is shorter) prior to initiation of study treatment
8. Major surgery within 4 weeks of the first dose of study drug. Note that all
surgical wounds must be healed and free of infection or dehiscence
9. Prior toxicities from chemotherapy, radiotherapy, and other anti-cancer
therapies, including immunotherapy that have not regressed to Grade ≤1 severity
(CTCAE v5.0) with the exception of alopecia, vitiligo and grade 2 peripheral
neurotoxicity
10. Potent inhibitors or inducers of CYP3A4 within 2 weeks before the first dose of
study treatment (3 weeks for St John's Wort). Refer to
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-
interactions-table-substrates-inhibitors-and-inducers for a list of drugs
11. Active central nervous system (CNS) metastases including presence of cerebral
edema, requirement for systemic steroid treatment, disease progression due to
intracranial lesions, leptomeningeal metastasis, and other clinical symptoms
related to CNS metastases
12. Impaired cardiac function or clinically significant cardiac disease, including
any one of the following:
1. New York Heart Association class III or IV heart disease, active ischemia or
any other uncontrolled cardiac condition such as angina pectoris, clinically
significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or
congestive heart failure,
2. Baseline prolongation of the rate-corrected QT interval based on repeated
demonstration of QTcF >470 ms (average of screening triplicates) or history of
long QT interval corrected (QTc) syndrome (Note: QTc interval corrected by
Fridericia's formula),
3. Left ventricular ejection fraction (LVEF) <50% or below the institutional lower
limit of normal (whichever is higher)
13. Known acquired immunodeficiency syndrome (AIDS)-related illness, or positive
test for HIV 1/2 antibody
14. Exclusion of hepatitis infection based on the following results and/or
criteria:
1. Active hepatitis B infection: positive tests for hepatitis B surface antigen
(HBsAg), or antibody to hepatitis B core antigen (anti-HBc). A patient with
positive tests for HBsAg or anti-HBc but with HBV-DNA measurements lower than
detectable (or per local practice) can be enrolled,
2. Active hepatitis C infection: positive Hepatitis C virus antibody. If positive
antibody to hepatitis C Virus (anti-HCV) is detected, Hepatitis C virus RNA by
polymerase chain reaction (PCR) is necessary. A patient with positive anti-HCV
but with a negative test for HCV RNA can be enrolled
15. Any of the following ophthalmological criteria:
1. Current evidence or previous history of retinal pigment epithelial detachment
(RPED) /Central serous retinopathy (CSR)
2. Previous laser treatment or intra-ocular injection for treatment of macular
degeneration
3. Current evidence or previous history of dry or wet age-related macular
degeneration
4. Current evidence or previous history of retinal vein occlusion (RVO)
5. Current evidence or previous history of retinal degenerative diseases (e.g.,
hereditary)
6. Diabetic retinopathy with macular edema
7. Current evidence or previous history of any other clinically relevant
chorioretinal defect
8. Uncontrolled glaucoma or intraocular pressure > 21 mmHg [after intervention per
local standard of care (SOC)]
9. History of systemic disease or ophthalmologic disorders requiring chronic use
of ophthalmic steroids
10. Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute
(within 4 weeks prior to first dose) or actively progressing
11. Current evidence or previous history of corneal pathology such as keratopathy,
corneal abrasion or ulceration, or current evidence of conjunctivitis
16. Patients with refractory/uncontrolled ascites or pleural effusion
17. Pregnant or nursing (lactating) women, where pregnancy is defined as the state
of a female after conception and until the termination of gestation, confirmed
by a positive human chorionic gonadotropin (hCG) laboratory test within 7 days
prior to the start of study drug
18. Non-surgically sterilized male or female patients of childbearing potential
must agree to use highly effective methods of birth control during the study
and for approximately 6 months after the last dose of study drug. A condom is
also required to be used by vasectomized men to prevent delivery of the drug
via seminal fluid
19. Vaccination with a live, attenuated vaccine within 4 weeks prior to the first
dose of study treatment except for administration of inactivate vaccines (e.g.,
COVID-19 vaccines, inactivated influenza vaccines)
20. Any other clinically significant comorbidities, such as uncontrolled pulmonary
disease, active infection, or any other condition, 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
21. Planned major surgery during study treatment
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UC San Diego Moores Cancer Center
Address:
City:
La Jolla
Zip:
92093
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nidhi Patel
Phone:
858-822-1962
Email:
nidpatel@health.ucsd.edu
Investigator:
Last name:
Peter Vu, MD
Email:
Principal Investigator
Facility:
Name:
Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kelly Schneider
Phone:
313-576-9749
Email:
schneidk@karmanos.org
Investigator:
Last name:
Anthony Shields, MD
Email:
Principal Investigator
Facility:
Name:
Comprehensive Cancer Centers of Nevada
Address:
City:
Las Vegas
Zip:
89119
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ann Lovelace
Phone:
702-952-3449
Email:
ann.lovelace@usoncology.com
Investigator:
Last name:
Liawaty Ho, MD
Email:
Principal Investigator
Facility:
Name:
Gabrail Cancer Center Research
Address:
City:
Canton
Zip:
44718
Country:
United States
Status:
Recruiting
Contact:
Last name:
Carrie Smith
Phone:
330-417-8231
Email:
csmith@gabrailcancercenter.com
Investigator:
Last name:
Nashat Gabrail, MD
Email:
Principal Investigator
Facility:
Name:
Chongqing University Cancer Hospital
Address:
City:
Chongqing
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yi Gong, MD
Investigator:
Last name:
Yi Gong, MD
Email:
Principal Investigator
Facility:
Name:
The First Affiliated Hospital of Henan University of Science & Technology
Address:
City:
Luoyang
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jun Yao, MD
Investigator:
Last name:
Jun Yao, MD
Email:
Principal Investigator
Facility:
Name:
The First Affiliated Hospital of Zhengzhou University
Address:
City:
Zhengzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Feng Wang, MD
Investigator:
Last name:
Feng Wang, MD
Email:
Principal Investigator
Facility:
Name:
Hubei Cancer Hospital
Address:
City:
Wuhan
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xinjun Liang, MD
Investigator:
Last name:
Xinjun Liang, MD
Email:
Principal Investigator
Facility:
Name:
Hunan Central Hospital
Address:
City:
Changsha
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Shusuan Jiang, MD
Investigator:
Last name:
Shusuan Jiang, MD
Email:
Principal Investigator
Facility:
Name:
The Affiliated Hospital of Inner Mongolia Medical University
Address:
City:
Hohhot
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Qun Hu, MD
Investigator:
Last name:
Qun Hu
Email:
Principal Investigator
Facility:
Name:
The First Affiliated Hospital of Nanchang University
Address:
City:
Nanchang
Country:
China
Status:
Recruiting
Contact:
Last name:
Xiaojun Xiang, MD
Investigator:
Last name:
Xiaojun Xiang, MD
Email:
Principal Investigator
Facility:
Name:
Jilin Cancer Hospital
Address:
City:
Changchun
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Ying Chen, MD
Investigator:
Last name:
Ying Chen, MD
Email:
Principal Investigator
Facility:
Name:
The First Hospital of China Medical University
Address:
City:
Shenyang
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jinglei Qu, MD
Investigator:
Last name:
Jinglei Qu, MD
Email:
Principal Investigator
Facility:
Name:
Shanghai East Hospital Tongji University
Address:
City:
Shanghai
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Ming Quan, MD
Investigator:
Last name:
Ming Quan, MD
Email:
Principal Investigator
Facility:
Name:
Shanxi Provincial Cancer Hospital
Address:
City:
Taiyuan
Country:
China
Status:
Recruiting
Contact:
Last name:
Yusheng Wang, MD
Investigator:
Last name:
Yusheng Wang, MD
Email:
Principal Investigator
Facility:
Name:
West China School of Medicine/West China Hospital of Sichuan University
Address:
City:
Chengdu
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Ye Chen, MD
Investigator:
Last name:
Ye Chen, MD
Email:
Principal Investigator
Facility:
Name:
Mianyang Central Hospital
Address:
City:
Mianyang
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xiaobo Du, MD
Investigator:
Last name:
Xiaobo Du, MD
Email:
Principal Investigator
Facility:
Name:
Zhejiang University Cancer Hospital
Address:
City:
Hangzhou
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Ji Zhu, MD
Investigator:
Last name:
Ji Zhu, MD
Email:
Principal Investigator
Facility:
Name:
Fujian Cancer Hospital (Department of Hepatobiliary and Pancreatic Oncology /Phase I Ward)
Address:
City:
FuZhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Jing Feng Liu, MD
Investigator:
Last name:
Jing Feng Liu, MD
Email:
Principal Investigator
Facility:
Name:
Harbin Medical University Cancer Hospital (Gastroenterology Department 2nd Ward)
Address:
City:
Haerbin
Country:
China
Status:
Recruiting
Contact:
Last name:
Yanqiao Zhang, MD
Investigator:
Last name:
Yanqiao Zhang, MD
Email:
Principal Investigator
Facility:
Name:
Zhongshan Hospital of Fudan University (Hepatological Surgery Department)
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Jian Zhou, MD
Investigator:
Last name:
Jian Zhou, MD
Email:
Principal Investigator
Facility:
Name:
Zhongshan Hospital of Fudan University (Medical Oncology Department)
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Tianshu Liu, MD
Investigator:
Last name:
Tianshu Liu, MD
Email:
Principal Investigator
Facility:
Name:
Liaoning Cancer Hospital (Phase I Ward)
Address:
City:
Shenyang
Country:
China
Status:
Recruiting
Contact:
Last name:
Yan Zhao, MD
Investigator:
Last name:
Yan Zhao, MD
Email:
Principal Investigator
Facility:
Name:
Yantai Yuhuangding Hospital (Department of Medical Oncology, 1)
Address:
City:
Yantai
Country:
China
Status:
Recruiting
Contact:
Last name:
Jian Chen, MD
Investigator:
Last name:
Jian Chen, MD
Email:
Principal Investigator
Start date:
June 26, 2023
Completion date:
June 30, 2025
Lead sponsor:
Agency:
Abbisko Therapeutics Co, Ltd
Agency class:
Industry
Source:
Abbisko Therapeutics Co, Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05627063
